The effect of antibody-dependent enhancement, cross immunity, and vector population on the dynamics of dengue fever.

Dengue is a major international public health concern and impacts one-third of the world's population. No specific vaccine and treatment are available for this vector-borne disease. There are four similar but distinct serotypes of dengue viruses (DENV). Infection with one serotype affords life-long immunity to that serotype but only temporary partial immunity, or cross immunity (CI), to others. This increases the risk of developing lethal complications upon re-infection, mainly because of the effect of antibody-dependent enhancement (ADE). There have been multiple studies of the dynamic behavior created by the interplay of ADE and CI using mathematical models. However, models in the literature seldom capture the vector population, which we consider important because combating the mosquito vector is the only way to contain dengue transmission in the absence of vaccines. We therefore propose two differential-equation models of dengue fever (DF) with different levels of complexity and details. Our results support the need for ADE to explain the complexity of the epidemiological data.

Photoradiation in the treatment of recurrent breast carcinoma.

Photoradiation, with the use of hematoporphyrin derivative (Hpd) activated by visible light in the red region of the spectrum, was an effective treatment for controlling local and regional chest wall recurrences of breast carcinoma. With sufficient time between iv injection of the drug and local activation with red light, cutaneous and subcutaneous masses were treated effectively without undue damage to overlying and adjacent skin. This high therapeutic ratio resulted from the ability to Hpd to accumulate and/or to be retained to a higher degree in malignant tissue than in many normal tissues. This technique can be used as a primary treatment or upon tumor recurrence following conventional modalities such as surgery, chemotherapy, and radiation therapy.

Cavitary pulmonary sarcoidosis.

A 25-year-old woman was initially seen with hilar adenopathy and bilateral cavitary lesions. No cause for these roentgenographic abnormalities other than sarcoidosis could be determined. In contrast to what is usually found in acute sarcoidosis, the bronchoalveolar lavage fluid from this patient contained a normal number of lymphocytes and an increased number of multinucleated giant cells. These findings raise the possibility that patients with acute sarcoidosis and cavitation have an atypical form of this disease. Even though cavitation in acute sarcoidosis is rare, this disorder must be considered in making the differential diagnosis of cavitary lung disease.

Relationship between plasma corticosterone and insulin levels in rats with ventromedial hypothalamic lesions.

The effects of ventromedial hypothalamic (VMH) lesions on plasma corticosterone, insulin, and glucose levels were studied in food-restricted and ad lib fed female rats. VMH lesions resulted in significant elevations of corticosterone and insulin levels compared to control values during the first 25 days after surgery. However, unlike insulin values which were generally greater in VMH rats fed ad lib than in food-restricted animals, plasma corticosterone levels were unaffected by level of food intake. Corticosterone and insulin levels were unrelated preoperatively and in sham-operated animals, but were positively correlated (r = .82) by Day 25 in ad lib fed VMH rats. It is concluded that the elevation in plasma glucocorticoids observed in VMH rats is a primary effect of the lesion that is independent of food intake or initial weight gain.

Randomized trial of chlorozotocin, neocarzinostatin, or methyl-CCNU in patients with malignant melanoma.

One hundred twenty-two patients with disseminated malignant melanoma were randomized using an unbalanced randomization to receive chlorozotocin, neocarzinostatin, or MeCCNU. Of the 114 evaluable patients, 46 received chlorozotocin, 47 received neocarzinostatin, and 21 received MeCCNU. The response rates to these three drugs were 9%, 4%, and 14% respectively. Median survival times were 4.2, 3.4, and 5.8 months respectively. Toxicity was acceptable with all three agents. Chlorozotocin and neocarzinostatin do not appear to offer any improved response rates over MeCCNU for patients with disseminated malignant melanoma.

From regional healthcare information organizations to a national healthcare information infrastructure.

Recently there has been increased focus on the need to modernize the healthcare information infrastructure in the United States. The U.S. healthcare industry is by far the largest in the world in both absolute dollars and in percentage of GDP (more than $1.5 trillion, or 15 percent of GDP). It is also fragmented and complex. These difficulties, coupled with an antiquated infrastructure for the collection of and access to medical data, lead to enormous inefficiencies and sources of error. Consumer, regulatory, and governmental pressure drive a growing consensus that the time has come to modernize the U.S. healthcare information infrastructure (HII). While such transformation may be disruptive in the short term, it will, in the future, significantly improve the quality, expediency, efficiency, and successful delivery of healthcare while decreasing costs to patients and payers and improving the overall experiences of consumers and providers. The launch of a national health infrastructure initiative in the United States in May 2004--with the goal of providing an electronic health record for every American within the next decade--will eventually transform the healthcare industry in general, just as information technology (IT) has transformed other industries in the past. The key to this successful outcome will be based on the way we apply IT to healthcare data and the services delivered through IT. This must be accomplished in a way that protects individuals and allows competition but gives caregivers reliable and efficient access to the data required to treat patients and to improve the practice of medical science. This paper describes key IT solutions and technologies that address the challenges of creating a nation-wide healthcare IT infrastructure. Furthermore we discuss the emergence of new electronic healthcare services and the current efforts of IBM Research, Software Group, and Healthcare Life Sciences to realize this new vision for healthcare.

Explaining the moon illusion.

An old explanation of the moon illusion holds that various cues place the horizon moon at an effectively greater distance than the elevated moon. Although both moons have the same angular size, the horizon moon must be perceived as larger. More recent explanations hold that differences in accommodation or other factors cause the elevated moon to appear smaller. As a result of this illusory difference in size, the elevated moon appears to be more distant than the horizon moon. These two explanations, both based on the geometry of stereopsis, lead to two diametrically opposed hypotheses. That is, a depth interval at a long distance is associated with a smaller binocular disparity, whereas an equal depth interval at a smaller distance is associated with a larger disparity. We conducted experiments involving artificial moons and confirmed the hypothesis that the horizon moon is at a greater perceptual distance. Moreover, when a moon of constant angular size was moved closer it was also perceived as growing smaller, which is consistent with the older explanation. Although Emmert's law does not predict the size-distance relationship over long distances, we conclude that the horizon moon is perceived as larger because the perceptual system treats it as though it is much farther away. Finally, we observe that recent explanations substitute perceived size for angular size as a cue to distance. Thus, they imply that perceptions cause perceptions.

On cortical folds and neuromagnetic fields.

A folded cortical source of neuromagnetic fields, similar in configuration to the visual cortex, was simulated. Cortical activity was modelled by different distributions of independent current dipoles. The map of the summed fields of the dipoles of this cruciform model changed, depending upon the statistical distribution of the electrical activity of the dipoles and its geometry. Arrays of dipoles of random orientations and strengths produced field patterns that could be interpreted as due to moving neural currents, although the geometry of the neural tissue remained unchanged and the average activity remained approximately constant. The field topography at any instant was apparently unrelated to the depth or orientation of the underlying structure, thus raising questions about how to interpret topographic MEG and EEG displays. Furthermore, asynchronous activity (defined as independent directions and magnitudes of activity of the dipoles) did not result in less field power than when the dipoles were synchronized, i.e., when the direction of current flow was correlated across all of the dipoles within the cruciform structure. Therefore, in this model 'alpha blockage' cannot be mimicked by desynchronization. More generally, for the cruciform or any other symmetrically folded and active cortical sheet, 'blockage' cannot be attributed to desynchronization. The same is true for the EEG except that smooth unfolded sheets of radially oriented dipoles would result in enhancement of voltage due to synchronization. Such radial dipoles do not contribute to the MEG. Blockage was simulated by reducing the amount of activity within different portions of the synchronized cruciform model. This resulted in a dramatic increase in the net field because attenuation broke the symmetry of the synchronized cruciform structure. With asynchronous dipoles populating the structure, the attenuation of the same portion of the structure had no easily discerned effect on the net field. However, maps of average field power were consistently related to the position of the region of attenuated activity. The locations of regions of attenuated activity were determined by taking the difference between the mean square field pattern obtained when all portions of the cruciform structure were active and the pattern obtained when a portion of the structure was relatively inactive. When activity of the same portions were incremented rather than attenuated, the resulting plot of average power was essentially the same as that of the attenuated portion derived by taking these differences between power distributions. The major conclusions are that the concepts of synchronization and desynchronization have no explanatory power unless the physical conditions under which they occur are specified precisely.(ABSTRACT TRUNCATED AT 400 WORDS)

Prednimustine therapy for advanced prostatic cancer.

23 patients with advanced, hormonal-resistant, prostatic cancer were treated with daily oral prednimustine--a combination of prednisolone and chlorambucil. 8 patients (35%) subjectively responded with disappearance of skeletal pain and improvement in appetite, weight and sense of well being. 3 patients had objective evidence of tumour regression. Clinical toxicity was moderate, and only occasional myelosuppression was encountered. The ease of administration and predictable toxicity of prenimustine make it a potentially useful agent, alone or in combination, for advanced prostatic cancer.

Nephrotic syndrome associated with gastric cancer.

A patient whose nephrotic syndrome was controlled by steroids and cyclophosphamide was found to have gastric cancer. After removal of the tumor and discontinuing the steroid therapy, no recurrence of the clinical signs of nephrotic syndrome appeared, but moderate proteinuria persisted. The literature regarding the association of nephrotic syndrome with malignancies is reviewed.

Sodium NMR evaluation of articular cartilage degradation.

One of the first effects of degenerative osteoarthritis is the loss of proteoglycans from the matrix of articular cartilage. Using a model of osteoarthritic change where the cartilage has been enzymatically degraded with trypsin, the sodium NMR characteristics of the cartilage were determined as a function of changes in the proteoglycan content. The results demonstrate that the single quantum sodium signal decreases as the proteoglycan content of the cartilage matrix decreases. In addition, the relaxation characteristics of the sodium change such that the T1 is longer, the T2s is longer, and the T2f is shorter. Short echo-time, T1-weighted sodium images are presented which demonstrate that this information may be utilized to detect the loss of proteoglycans from articular cartilage.

Water distribution patterns inside bovine articular cartilage as visualized by 1H magnetic resonance imaging.

OBJECTIVE: To develop a magnetic resonance imaging (MRI) technique to non-invasively map water volume fraction (WVF) in articular cartilage. Special emphasis was placed on spatial resolution and temporal considerations, aimed at creating a procedure feasible for eventual human studies. DESIGN: Absolute proton density MR images of intact, ex vivo bovine patellae were calculated from fully T(1) relaxed, short echo time images. This was accomplished through compensation for T(2) decay with calculated T(2) maps. Calibration of the signal intensity in the image was accomplished with the use of H2O:D2O phantoms, where the WVF was varied from 0.95 to 0.75. Application of the calibration curve to the entire image yielded images that represent WVF on a pixel by pixel basis. Calculations of water content by weight were performed by considering the density of the solid content. RESULTS: Using four echo time points, experiments comparing MR images from single-echo and multi-echo spin echo sequences yielded similar results. T(2) decreased with depth through the cartilage, with a maximum at the articular surface of approx 100 ms, and a approximately 50 ms minimum at the bone/cartilage interface. The WVF through the depth of the cartilage showed a similar trend, decreasing from 0.9 at the surface, to 0.7 at the bone/cartilage interface. Translation to a weight percent yielded approximately 86% weight at the surface, trending down to approximately 63% at the bone/cartilage interface, with an average of 74.5% for five patellae. These MRI derived values were compared to the measured weight of water in excised cartilage plugs from the same patellae and showed remarkably close agreement. CONCLUSION: We have demonstrated that MRI can non-invasively map WVF in cartilage in a pixel by pixel manner. This was accomplished in a time span that was clinically feasible, allowing the routine use of this method in a clinical setting. Moreover, this procedure employed standard MRI equipment and pulse sequences, avoiding the need for hardware modifications and using simple post processing methods. However, baseline studies need to be performed prior to incorporation into a standard radiological evaluation. Implications in the diagnosis of osteoarthritis (OA) are discussed.

The importance of initial presentation and treatment upon the survival of patients with chondrosarcoma.

The effect of initial presenting symptoms, degree of tumor differentiation and type of surgical procedure on survival was evaluated in a 20 year review of 42 patients with chondrosarcoma. Therapy of patients presenting initially with a painless mass resulted in a median survival period longer than 13 years versus less than three years of the initial symptom was pain. Median survival time of patients with well differentiated chondrosarcomas was more than ten years compared with 1.2 years if the tumor was less well differentiated. Even if the sarcoma was nonresectable, these factors influenced the survival time. Since chondrosarcomas tended to recur locally rather than to metastasize, a number of patients who had a recurrence after the initial surgical excision could be saved by a more radical secondary operation.

Preliminary clinical study of prednimustine in lung cancer.

Prednimustine is a prednisolone ester of chlorambucil which has been found effective in a variety of tumors. Eleven patients with advanced carcinoma of the lung (5 adenocarcinoma, 3 squamous cell carcinoma, 2 small cell carcinoma and 1 large cell carcinoma) were treated at a dosage of 40 mg. per day. Nine had previously failed on combination chemotherapy. No objective responses were observed. Leukopenia or thrombocytopenia were found in 4 patients with nadirs of 2,000 WBC and 60,000 platelets. The lack of response may be a function of the inability of lung carcinoma to concentrate the drug as shown with radioactive labeled Prednimustine. The malignant cells may lose their glucocorticoid binding capacity normally present in the lung. Determination of glucocorticoid binding capacity or Prednimustine uptake might predict the effectiveness of Prednimustine in the treatment of tumor. Prednimustine was well tolerated and may be given safely in advanced malignancies. Further studies with high intermittent doses and selection of tumors with steroid binding properties are now in progress.

Lymphosarcoma. A comparison of extended to conservative chemotherapy.

Sixty-three patients with Stage III and IV lymphocytic lymphoma were randomized for induction treatment between a single course of nitrogen mustard and a 14-day course of prednisone (conservative therapy) or sequential rotation of BCNU, nitrogen mustard and cytoxan with intermittent vincristine and prednisone for 6 months (extended therapy). Maintenance therapy by an oral alkylating agent (cytoxan or chlorambucil) with or without prednisone was given. Complete remission occurred in 75% of the conservative and 77% of the extended therapy group. The median duration of remission was similar, and greater than 27 months in both groups, and there was no difference in survival. At 1 year 80% of patients with no prior chemotherapy were in remission vs. 47% of patients with prior chemotherapy (p less than .01). No significant advantage for extended chemotherapy was found. The addition of vincristine was not helpful in induction and prednisone during maintenance did not improve the duration of remission or survival.

Sodium and proton MR properties of cartilage during compression.

Proton and sodium MR relaxation times of bovine articular cartilage specimens were measured as a function of proteoglycan (PG) depletion and as a function of mechanical compression. Proton and sodium relaxation times of normal cartilage were compared with relaxation times of PG-depleted cartilage to evaluate the significance of PG depletion-induced changes in MR relaxation parameters. These comparisons were conducted for both uncompressed and mechanically compressed states. The mechanical compressions were performed with an MR-compatible pressure cell and evaluated dynamically via interleaved one-dimensional proton and sodium MR projection imaging. The comparisons indicate that sodium relaxation parameters are sensitive to PG depletion when cartilage is in a mechanically compressed state or an uncompressed state. In contrast, proton relaxation parameters do not change significantly with PG depletion when cartilage is in an uncompressed state. However, during mechanical compression, proton T2 becomes sensitive to PG depletion. These results support the potential of sodium magnetic resonance imaging (MRI) as a possible modality for obtaining imaging contrast related to PG depletion. The results also indicate the potential of proton MRI to provide such contrast if the image acquisition is conducted in conjunction with a mechanical compression via physical exercise.J. Magn. Reson Imaging 10:961-967, 1999.

A novel approach to observing articular cartilage deformation in vitro via magnetic resonance imaging.

The design of a pressure cell that compresses a cartilage specimen in one dimension within an imaging magnet is presented. One-dimensional projection images in a direction perpendicular to the articular surface of the cartilage specimen were used to generate a uniaxial confined deformation creep curve for normal and trypsin-degraded cartilage specimens during a continuous 0.690 MPa (100 psi) pressure application. The resulting curves are shown to fit a two time constant viscoelastic model well and also indicate that the elastic modulus of cartilage decreases and the deformation rate increases upon trypsin proteolysis. Furthermore, cartilage permeability is shown as a function of cartilage strain for both the normal and trypsin-degraded case. Several two-dimensional slice-selective images were collected both before and after 80 minutes of continuous compression. These images were used to evaluate the relative changes in the spin-lattice, T1, and spin-spin, T2, relaxation time constant maps for both normal and degraded cartilage specimens in response to compression. The results of this study demonstrate the utility of a novel, non-magnetic, cartilage compression device and also support the validity of a simple two-component rheological model of articular cartilage.

Sodium multiple quantum spectroscopy of articular cartilage: effects of mechanical compression.

The effects of mechanical compression on the multiple quantum coherences generated from sodium ions in articular cartilage were investigated. Cartilage samples obtained from bovine patellae were studied during compression at 0.7 MPa (100 psi) for 1 hour. The double quantum filtered spectra showed marked lineshape changes in the compressed samples. Compression did not seem to influence the lineshapes of the single quantum and triple quantum filtered spectra significantly. We found that the residual quadrupolar interaction was reduced in the compressed samples. Changes in the ordering of collagen fibers may be responsible for the observed effect.

T1rho-relaxation in articular cartilage: effects of enzymatic degradation.

Spin-lattice relaxation in the rotating frame (T1rho) dispersion spectroscopy and imaging were used to study normal and enzymatically degraded bovine articular cartilage. Normal specimens demonstrate significant T1rho "dispersion" (approximately 60 to approximately 130 ms) in the 100 Hz to 9 kHz frequency range. Proteoglycan-degraded specimens have 33% greater T1rho values than collagen-degraded or normal samples. T1rho-weighted images reveal structure not found in conventional T1- or T2-weighted images. Our results suggest that T1rho measurements are selectively sensitive to proteoglycan content. The potential of this method in distinguishing the early degenerative changes in cartilage associated with osteoarthritis is discussed.