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Biomedical subjects

J Sachs

Publications and source records attributed to J Sachs.

At least 19 recordsLinked to original sources

Defining and refining international donor support for combating the AIDS pandemic.

The international aid effort against AIDS is greatly incommensurate with the severity of the epidemic. Drawing on the data that international aid donors self-reported to the Organization for Economic Cooperation and Development (OECD), we find that, between 1996 and 1998, finance from all rich countries to sub-Saharan Africa for projects designated as AIDS control averaged US $69 million annually, and, assuming a safe margin for under-reporting and misreporting, we estimate that total donor spending on HIV/AIDS control was perhaps twice that at most. Since the late 1980s, aid levels have dropped relative to the prevalence of HIV infection, and stood recently at about $3 per HIV-infected person. Lack of finance is now the primary constraint on progress against AIDS, notwithstanding the widespread belief that a lack of interest from the goveements of poor countries is limiting. We argue that to produce a meaningful response to the pandemic, international assistance must be based on grants, not loans, for the poorest countries; be increased within the next 3 years to a minimum of $7.5 billion or more; be directed toward funding projects which are proposed and desired by the affected countries themselves, and which are judged as having epidemiological merit against the pandemic by a panel of independent scientific experts; and fund concurrent needs, including prevention, drug treatment (such as highly active antiretroviral therapy), and blocking mother-to-child HIV transmission. An effort of this scope and scale will both radically alter the prospects for intervention against AIDS in poor countries, and together with comparable efforts to control other infectious diseases, is easily afforded by the OECD donor economies, whose aggregate national income recently surpassed $21 trillion annually.

Acquired Immunodeficiency Syndrome↗

The fusion of anatomic and physiologic imaging in the management of patients with cancer.

Imaging is of major clinical importance in the noninvasive evaluation and management of patients with cancer. Computed tomography (CT) and other anatomic imaging modalities, such as magnetic resonance imaging (MRI) or ultrasound, have a high diagnostic ability by visualizing lesion morphology and by providing the exact localization of malignant sites. Nuclear medicine provides information on the function and metabolism of cancer. Over the last decade, there have been numerous attempts to combine data obtained from different imaging techniques. Fused images of nuclear medicine and CT (or to a lesser extent, MRI) overcome the inherent limitations of both modalities. Valuable physiologic information benefits from a precise topographic localization. Coregistered data have been shown to be useful in the evaluation of patients with cancer at diagnosis and staging, in monitoring the response to treatment, and during follow up, for early detection of recurrence. Time-consuming and difficult realignment and computation for fusion of independent studies have, until now, limited the use of registration techniques to pilot studies performed in a small number of patients. The development of the new technology of single photon emission computed tomography/CT and positron emission tomography/CT that allows for combined functional and anatomic data acquisition has the potential to make fusion an everyday clinical tool.

Diagnostic Imaging↗

The new technology of combined transmission and emission tomography in evaluation of endocrine neoplasms.

UNLABELLED: The clinical value of a novel technology of combined transmission and emission tomography (TET) was assessed in patients with endocrine tumors. METHODS: TET technology, which combines simultaneous acquisition of SPECT and CT images, using the same imaging device, allows correct fusion of images of both modalities. TET was performed on 27 patients with known or suspected endocrine tumors. The radiopharmaceuticals used for the emission part of the study were chosen according to the tumor type: (111)In-octreotide for patients with neuroendocrine tumors (n = 10), (99m)Tc-sestamibi for patients with primary hyperparathyroidism (n = 8), (131)I for patients with thyroid cancer (n = 4), and (123)I-metaiodobenzylguanidine and (75)Se-cholesterol for patients with adrenal masses (n = 3 and n = 2, respectively). The additional information provided by TET compared with scintigraphy was assessed for both image interpretation and clinical utility. RESULTS: TET did not provide any additional data in 16 patients (59%), including 5 patients with normal scintigraphy. In 11 patients (41%) with abnormal SPECT findings, TET improved image interpretation by providing a better anatomic localization of SPECT-detected lesions. It showed unsuspected bone involvement in 4 patients, it identified the organs involved and the relationship of the lesions to neighboring structures in 5 patients, and it differentiated physiologic uptake from tumor uptake in 2 patients. TET provided additional information of clinical value in 9 patients (33%). It assisted in better planning of surgery in 2 patients with neuroendocrine tumors and in 2 patients with ectopic parathyroid adenomas. It changed the treatment approach in 2 patients with neuroendocrine tumors and 1 patient with thyroid carcinoma, and it altered prognosis in 2 patients with thyroid malignancy. CONCLUSION: TET enhances the already unique role of nuclear medicine procedures in the assessment and management of patients with endocrine neoplasms.

3-Iodobenzylguanidine↗

Dipole lattice membrane model for protein calculations.

A dipole lattice model for lipid membranes and their interactions with peptides is presented. It uses the Langevin dipole method to calculate electrostatic interactions in the heterogeneous membrane environment. A series of test cases are presented, including spherical charges, dipoles, side chain analogs, and helical peptides. The model consistently produces qualitatively correct results.

Alamethicin↗

Motivational Beliefs, Study Strategies, and Mathematics Attainment in High- and Low-Achieving Chinese Secondary School Students.

In order to examine the relationship between cognitive and motivational variables and their relationship to mathematics attainment, Hong Kong-Chinese students enrolled in schools for high-, average-, and low-achievers completed questionnaires in Year 10 and in Year 11. Low-achievers perceived academic learning as being less useful over time and reported spending less time studying in Year 10 than in Year 11 but high- and low-achievers did not differ on their use of self-regulated learning strategies. Performance on the public examination in mathematics was predicted by prior achievement and Self-Concept of Mathematics Ability. Results underscore the importance of considering cultural beliefs systems and educational systems in models of academic motivation. Copyright 2000 Academic Press.

Journal Article↗

Item-level and subscale-level factoring of Biggs' Learning Process Questionnaire (LPQ) in a mainland Chinese sample.

BACKGROUND: The learning process questionnaire (LPQ) has been the source of intensive cross-cultural study. However, an item-level factor analysis of all the LPQ items simultaneously has never been reported. Rather, items within each subscale have been factor analysed to establish subscale unidimensionality and justify the use of composite subscale scores. AIMS: It was of major interest to see if the six logically constructed items groups of the LPQ would be supported by empirical evidence. Additionally, it was of interest to compare the consistency of the reliability and correlational structure of the LPQ subscales in our study with those of previous cross-cultural studies. METHODS: Confirmatory factor analysis was used to fit the six-factor item level model and to fit five representative subscale level factor models. SAMPLE: A total of 1070 students between the ages of 15 to 18 years was drawn from a representative selection of 29 classes from within 15 secondary schools in Guangzhou, China. Males and females were almost equally represented. RESULTS: The six-factor item level model of the LPQ seemed to fit reasonably well, thus supporting the six dimensional structure of the LPQ and justifying the use of composite subscale scores for each LPQ dimension. However, the reliability of many of these subscales was low. Furthermore, only two subscale-level factor models showed marginally acceptable fit. Substantive considerations supported an oblique three-factor model. CONCLUSIONS: Because the LPQ subscales often show low internal consistency reliability, experimental and correlational studies that have used these subscales as dependent measures have been disappointing. It is suggested that some LPQ items should be revised and other items added to improve the inventory's overall psychometric properties.

Achievement↗

Using a small sample Q sort to identify item groups.

A small sample of 40 second-year university students in Hong Kong were asked to perform a Q sort on the 36 items of a questionnaire used to assess six dimensions of student approaches to learning, the Learning Process Questionnaire. Participants were instructed to sort the items into as many groups as they liked with the only conditions being that all items within a group be as similar as possible in perceived meaning and that no item be placed into more than one group. By treating participants' responses as a form of multiple-choice data and by applying optimal scaling, three solutions were obtained. A two-dimensional plot of the optimal item scores for the first two solutions yielded 10 clearly defined item clusters suggesting a possible ten-factor model as opposed to the six-factor model found in studies of this questionnaire. The implications of using this approach to identify potential competing factor models, especially within a cross-cultural context, are discussed.

Adult↗

Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity.

The tumor-associated-Ag MART-1 is expressed by most human melanomas. The genes encoding an alphabeta TCR from a MART-1-specific, HLA-A2-restricted, human T cell clone have been efficiently transferred and expressed in human PBL. These retrovirally transduced PBL cultures were MART-1 peptide reactive, and most cultures recognized HLA-A2+ melanoma lines. Limiting dilution clones were generated from three bulk transduced PBL cultures to investigate the function of individual clones within the transduced cultures. Twenty-nine of 29 CD8+ clones specifically secreted IFN-gamma in response to T2 cells pulsed with MART-1(27-35) peptide, and 23 of 29 specifically secreted IFN-gamma in response to HLA-A2+ melanoma lines. Additionally, 23 of 29 CD8+ clones lysed T2 cells pulsed with the MART-1(27-35) peptide and 15 of 29 lysed the HLA-A2+ melanoma line 888. CD4+ clones specifically secreted IFN-gamma in response to T2 cells pulsed with the MART-1(27-35) peptide. TCR gene transfer to patient PBL can produce CTL with anti-tumor reactivity in vitro and could potentially offer a treatment for patients with metastatic melanoma. This approach could also be applied to the treatment of other tumors and viral infections. Additionally, TCR gene transfer offers unique opportunities to study the fate of adoptively transferred T cells in vivo.

Antigens, Neoplasm↗

Lymphohematopoietic graft-vs.-host reactions can be induced without graft-vs.-host disease in murine mixed chimeras established with a cyclophosphamide-based nonmyeloablative conditioning regimen.

Mixed hematopoietic chimerism can be induced in mice receiving allogeneic bone marrow transplantation (BMT) after nonmyeloablative host conditioning with depletion T cells with of anti-T cell monoclonal antibodies (mAbs), low-dose (3 Gy) total-body irradiation (TBI), and local thymic irradiation (7 Gy). These mice are specifically tolerant to donor and host antigens. When nontolerant donor T cells are given to chimeras several months after BMT, full donor-type chimerism develops, but graft-vs.-host disease (GVHD) does not occur. The induction of such lymphohematopoietic GVH reactions without GVHD could provide an approach to separating graft-vs.-leukemia (GVL) from GVHD in patients with hematologic malignancies. To make the nonmyeloablative conditioning regimen described above more cytoreductive for such malignancies, we have now modified it by replacing TBI with cyclophosphamide (CP). Treatment with anti-CD4 and anti-CD8 mAbs on day -5, 200 mg/kg CP on day -1, and 7 Gy thymic irradiation on day 0 was only slightly myelosuppressive and allowed fully major histocompatibility complex (MHC)-mismatched (with or without multiple minor antigen disparities) allogeneic bone marrow to engraft and establish long-term mixed chimerism in 40 to 82% of recipients in three different strain combinations. The administration of nontolerant donor spleen cells at 5 weeks or at 5, 8, and 11 weeks posttransplant was capable of eliminating host hematopoietic cells, leading to full or nearly full donor chimerism in six of six and two of four chimeric animals in two different strain combinations. No clinical evidence of GVHD was observed in any recipients of these donor leukocyte infusions (DLI). These studies demonstrate that induction of mixed chimerism with nonmyeloablative conditioning followed at appropriate times by DLI might allow lymphohematopoietic GVH reactions, and hence GVL effects, to eliminate chronic hematologic malignancies without causing clinically significant GVHD.

Animals↗

[Digital storage phosphor mammography in a magnification technic: experimental studies for spatial resolution and for detection of microcalcifications].

PURPOSE: Since the routine use of storage phosphor systems for mammography has been limited by its inadequate spatial resolution of 5 linepairs/mm, a combination of a magnification mammography technique with storage phosphor plates was investigated to detect microcalcifications. MATERIAL AND METHODS: A new mammography system with a microfocus tube using an anode of 0.05-0.12 mm allowed to obtain survey views of the breast with 1.7x magnification (m), and spot views with 4x magnification. The digital image receptor comprised a high resolution storage phosphor plate. To determine spatial resolution, contrast transfer curves were obtained, and the detection of microcalcifications was investigated by ROC (receiver operating characteristic) analysis. RESULTS: Spatial resolution for digital survey views (m = 1.7) was 8 linepairs/mm and for spot views (m = 4) was 18 linepairs/mm. ROC analysis demonstrated a significantly higher performance of the digital magnification technique compared to the conventional screen-film mammography technique. CONCLUSIONS: The limitations of digital mammography with respect to spatial resolution can be overcome by using a high magnification technique.

Breast Diseases↗

The pharmacological effect of sodium phosphate after absorption from the peritoneal cavity.

Hyperosmolar solutions are frequently used in clinical practice for enemas. In a review of the literature we found 43 published cases of severe complications connected with the use of hyperosmolar enemas. The absorption of sodium phosphate led to a raise of the temperature up to 41.1 degrees C, massive acidosis and electrolyte disturbances with hypocalcemia and hypernatremia. The clinical picture was dominated in most of the cases by somnolence or coma. In our experiment the absorption of sodium phosphate from the peritoneal cavity of rats led to similar clinical symptoms and--depending on the amount of sodium phosphate absorbed--to the death of the animals. Hypovolemia, hypernatremia, hypocalcemia and a direct toxic effect of phosphate on the kidneys is responsible for the complex mode of intoxication. Sodium phosphate solutions should not be used in patients with inflammatory bowel disease with a high risk of laceration of the mucosa or perforation of the bowel.

Animals↗

Autoimmunity--towards the year 2001.

The interactive roles of T cells, major histocompatibility complex (MHC) class I and II molecules and antigen-presenting cells in the generation of autoimmunity is the subject of much discussion. A recent symposium contributed to the debate by inviting experts in several fields of immunology to answer specific questions relating to the mechanisms that trigger autoimmunity.

Animals↗

A ligand-epitope in vitro analysis of major histocompatibility determinants expressed on B and T lymphocytes.

Human histocompatibility leucocyte antigen (HLA)-specific monoclonal antibody probes were used to determine the affinity constant, and cell-surface density of HLA class I and class II determinants. The measurements were estimated for single-cell units of B-lymphoblastoid cell line (B-LCL) and cloned activated T cells in different functional states. Each HLA subset showed unimodal affinity constant values for the interaction with the corresponding HLA-specific antibodies. Such values ranged between 2.2 x 10(7) M-1 (class I) and 4.0 x 10(7) M-1 (class II) for different histocompatibility epitopes. In both B and T cells there was a rank order of epitope expression, class I being highly expressed (5 x 10(6) epitopes/cell) followed by DR, DQ and DP, (1.1-3.0 x 10(6) epitopes/cell). Suppressive clones carrying functionally defined stimulating determinants previously designated 'DY' carried similar numbers of DR, DQ and DP binding sites to DY- non-suppressive clones, but showed selective increases of class II determinants reactive with broad class II-specific antibodies. The results are discussed in the context of the functional consequences of different patterns of HLA epitope expression in immune responses.

Antibodies, Monoclonal↗