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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 199 records · Page 11Linked to original sources

[A cost analysis of diagnostic screening for the differentiation of type-1 and type-2 diabetics aged 30 to 45. A health economics modelling calculation].

BACKGROUND AND OBJECTIVE: Because of its chronic course and increasing incidence diabetes mellitus is assuming increasing importance not only for medical reasons but also on health policy. Early recognition of carriers of autoantibodies among type 2 diabetics (noninsulin-dependent; NIDDM) and the resulting optimization of blood glucose could lead to a reduction of secondary diseases. A health-economic model for calculating costs was used to test the socioeconomic significance of a screening programme for identifying carriers of antibodies against glutamic acid decarboxylase among NIDDM diabetics. PATIENTS AND METHODS: Health-economic analysis was based on the incidence of positive autoantibody tests among diabetics aged between 30 and 45 years. Results for a cohort of diabetics who had been screened were compared with those obtained in a control group without screening. A time-span of 20 years was chosen because of the late manifestations of diseases secondary to DM. The model calculations used a cost analysis. Data were based on interventional clinical and epidemiological studies. Cost of treatment of secondary diseases was confined to a one-year period. In the first instance the direct medical costs and additionally the indirect economic costs, generated by patients' loss of production and disability to work were calculated. One-dimensional sensitivity analysis was used to check the assumptions underlying the model. RESULTS: Per patient in the model, total costs of the screening programme over a period of 20 years were calculated at DM 31,278, of which DM 7,799 were direct and DM 23,479 indirect costs. The calculated costs for the control subjects (no screening) were DM 35,290, of which DM 10,984 were direct and DM 24,306 indirect costs. CONCLUSIONS: Extrapolating to the entire population, with an investment by the statutory health insurance of ca. DM 22.8 million, employing a full screening programme would lead to a saving of DM 2.6 billion.

Adult↗

Maintenance of genomic imprinting at the Arabidopsis medea locus requires zygotic DDM1 activity.

In higher plants, seed development requires maternal gene activity in the haploid (gametophytic) as well as diploid (sporophytic) tissues of the developing ovule. The Arabidopsis thaliana gene MEDEA (MEA) encodes a SET-domain protein of the Polycomb group that regulates cell proliferation by exerting a gametophytic maternal control during seed development. Seeds derived from female gametocytes (embryo sacs) carrying a mutant mea allele abort and exhibit cell proliferation defects in both the embryo and the endosperm. In this study we show that the mea mutation affects an imprinted gene expressed maternally in cells of the female gametophyte and after fertilization only from maternally inherited MEA alleles. Paternally inherited MEA alleles are transcriptionally silent in both the young embryo and endosperm. Mutations at the decrease in DNA methylation1 (ddm1) locus are able to rescue mea seeds by functionally reactivating paternally inherited MEA alleles during seed development. Rescued seeds are larger than the wild type and exhibit some of the abnormalities found in aborting mea seeds. Our results indicate that the maintenance of the genomic imprint at the mea locus requires zygotic DDM1 activity. Because DDM1 encodes a putative chromatin remodeling factor, chromatin structure is likely to be interrelated with genomic imprinting in Arabidopsis.

Alleles↗

Selecting among health-related quality-of-life instruments.

A method of evaluating health-related quality-of-life (HRQL) instruments is described. Selection of an HRQL instrument should be based on the intended purpose and how well the instrument satisfies that purpose. An available methodological framework for developing HRQL instruments can be used; its premise is that the developmental process and psychometric properties of an instrument vary with the intended purpose. Intended purposes are classified as evaluative, discriminative, and predictive. Developmental steps are selection of items, item scaling, item reduction and assessment of internal consistency, and determination of reliability, validity, and responsiveness. Specific criteria apply to each step. An evaluation of asthma-specific HRQL instruments demonstrates use of the method. A useful method exists for selecting among available HRQL instruments on the basis of the instruments' intended purposes.

Asthma↗

Potent activity of soluble B7-IgG fusion proteins in therapy of established tumors and as vaccine adjuvant.

Fusion proteins consisting of the extracellular region of murine B7.1 or B7.2 and the Fc portion of murine IgG2a (B7-IgG) were evaluated for their ability to promote antitumor responses. Therapeutic administration of soluble B7-IgG in mice with established tumors induced complete regression of the tumor and increased the survival of mice. In three models, MethA, P815, and MB49, mice with 7-day-old established tumors were cured with two to three treatment cycles of B7-IgG, given twice a week. Even in mice with an established B16/F10 tumor (a poorly immunogenic melanoma), therapeutic treatment with B7-IgG alone slowed tumor growth and increased survival significantly. Still stronger antitumor activity was achieved when B7-IgG was used as a vaccine adjuvant mixed with irradiated tumor cells. In 80% of mice with 7-day-old B16 tumors, tumors regressed completely, and mice survived for at least 80 days. In all tumor models, B7.1-IgG and B7.2-IgG had similar antitumor activity. B7-IgG-mediated tumor rejection was dependent on T cells, specifically CD8 cells, as demonstrated by the failure of B7-IgG to induce tumor regression in severe combined immunodeficient or CD8-depleted mice. In addition, mice that were cured of an established tumor were protected against a rechallenge with the same tumor for at least 4 months, suggesting the generation of memory responses. Surprisingly, the antitumor activity of B7-IgG was independent of IFN-gamma, as demonstrated by tumor rejection in IFN-gamma knockout mice. Our findings demonstrate the potent capacity of B7-IgG to generate or enhance antitumor immune responses and suggest the clinical value of B7-IgG.

Adjuvants, Immunologic↗

Cost-effectiveness of clozapine in patients with high and low levels of hospital use. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examined the relationship between pretreatment hospital use and the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. METHODS: Data from a 15-site randomized clinical trial were used to compare clozapine with haloperidol in hospitalized Veterans Affairs patients with refractory schizophrenia (n = 423). Outcomes were compared among those with many days in the hospital use (hereafter, high hospital users) (n = 141; mean = 215 psychiatric hospital days in the year prior to study entry) and those with few days in the hospital use (hereafter, low hospital users) (n = 282; mean = 58 hospital days). Analyses were conducted with the full intention-to-treat sample (n = 423) and with crossovers excluded (n = 291). RESULTS: Clozapine treatment resulted in greater reduction in hospital use among high hospital users (35 days less than controls, P = .02) than among low users (21 days less than controls, P = .05). Patients taking clozapine also had lower health care costs; after including the costs of both medications and other health services, costs were $7134 less than for controls among high hospital users (P = .14) but only $759 less than for controls among low hospital users (P = .82). Clinical improvement in the domains of symptoms, quality of life, extrapyramidal symptoms, and a synthetic measure of multiple outcomes favored clozapine in both high and low hospital user groups. CONCLUSIONS: Substantial 1-year cost savings with clozapine are observed only among patients with very high hospital use prior to initiation of treatment while clinical benefits are more similar across groups. Cost-effectiveness evaluations, and particularly studies of expensive treatments, cannot be generalized across type of use groups.

Adult↗

The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes.

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.

ADP-ribosyl Cyclase↗

Family 10 and 11 xylanase genes from Caldicellulosiruptor sp. strain Rt69B.1.

Three family 10 xylanase genes (xynA, xynB, and xynC) and a single family 11 xylanase gene (xynD) were identified from the extreme thermophile Caldicellulosiruptor strain Rt69B.1 through the use of consensus PCR in conjunction with sequencing and polyacrylamide gel electrophoresis. These genes appear to comprise the complete endoxylanase system of Rt69B.1. The xynA gene was found to be homologous to the xynA gene of the closely related Caldicellulosiruptor strain Rt8B.4, and primers designed previously to amplify the Rt8B.4 xynA gene could amplify homologous full-length xynA gene fragments from Rt69B.1. The complete nucleotide sequences of the Rt69B.1 xynB, xynC, and xynD genes were obtained using genomic walking PCR. The full-length xynB and xynC genes are more than 5 kb in length and encode highly modular enzymes that are the largest xylanases reported to date. XynB has an architecture similar to the family 10 xylanases from Thermoanaerobacterium saccharolyticum (XynA) and Clostridium thermocellum (XynX) and may be cell wall associated, while XynC is a bifunctional enzyme with an architecture similar to the bifunctional beta-glycanases from Caldicellulosiroptor saccharolyticus. The xynD gene encodes a two-domain family 11 xylanase that is identical in architecture to the XynB family 11 xylanase from the unrelated extreme thermophile Dictyoglomus thermophilum strain Rt46B.1. The sequence similarities between the Rt69B.1 xylanases with respect to their evolution are discussed.

Bacteria, Anaerobic↗

The Development of a Technique for Radiofrequency Lesioning of Splanchnic Nerves.

This article describes the development of a technique for radiofrequency lesioning of the splanchnic nerves. It features point neurolysis and improvement in safety from previously described techniques with the use of a curved, blunt needle. After extensive anatomic studies, the site of entry has been identified 4 cm lateral to the spinous process at the costovertebral angle of either the T11 or T12 vertebral body, and the placement of the needle tip at the junction of posterior two thirds to the anterior one third of the vertebral body. The use of a sharp, straight needle has been discouraged to prevent pneumothorax, and bowel, kidney, or nerve root injury. The radiofrequency lesion permits a point neurolysis, thus decreasing the rate of complications. Our experience of 22 patients treated with this technique has been complication-free, and the outcome was effective for all 10 patients with cancer. In the nonmalignancy group, some patients needed a second neurolysis (radiofrequency) procedure 4 months apart. There were also no secondary complications in these patients. We expect multicenter data accumulation in the coming years, which will determine the true efficacy of the radiofrequency of splanchnic nerves.

Journal Article↗

A randomized, prospective, controlled study of laparoscopic dye studies and selective salpingography as diagnostic tests of fallopian tube patency.

OBJECTIVE: To determine and compare the relative merits of laparoscopic dye (LD) studies and selective salpingography (SS) as diagnostic tests of fallopian tube patency. DESIGN: Randomized, prospective, controlled study. SETTING: University-associated assisted reproduction unit. PATIENT(S): Two hundred seventy-eight women undergoing investigation of infertility. INTERVENTION(S): Allocation to the performance of either LD studies followed by SS or SS followed by LD studies conducted sequentially under general anesthesia. MAIN OUTCOME MEASURE(S): Detection of fallopian tube occlusion, including the site of obstruction and evidence of peritubal or pelvic disease. RESULT(S): When diagnosis was compared by the first test used, 16 (11.9%) of 135 patients had proximal tubal occlusion at LD studies versus 5 (3.6%) of 138 at SS. Twelve (5.6%) of 122 patients had distal tubal occlusion at LD studies versus 14 (10.5%) of 133 at SS. Fifteen (11.1%) of 135 patients had peritubal disease at LD studies versus 3 (2.52%) of 119 at SS. When diagnosis was compared by individual tubes, the results were similar. Among patients who had proximal occlusion and otherwise normal tubes by both methods, endometriosis was present in 72.2%. CONCLUSION(S): Selective salpingography is a better diagnostic test of proximal tubal occlusion than are LD studies. There is no difference between SS and LD studies as a diagnostic test of distal tubal occlusion. Laparoscopic dye studies are a better diagnostic test for assessing peritubal disease than is SS. There may be an association between endometriosis and proximal tubal occlusion. Selective salpingography and LD studies are complementary investigations of the fallopian tubes.

Adult↗

Transacting self-preservation: a grounded theory of the spiritual dimensions of people with terminal cancer.

This study describes the spiritual meanings people with terminal cancer give to their everyday life-experiences. Transcriptions from semi-structured, in-depth interviews of 19 adults who had a diagnosis of cancer and who were living in Queensland and New South Wales, Australia, were analysed using the constant comparative approach of grounded theory. The study found that people with terminal cancer develop a spiritual perspective that strengthens their approaches to life and death. Their discovery of spiritual meaning is enacted through a process of transacting self-preservation. This process incorporates three phases, taking it all in, getting on with things and putting it all together. As people with terminal cancer move through these phases they transact self-preservation by discovering deeper levels of understanding self. This discovery of self incorporates a higher level of spiritual growth, spiritual perspective, spiritual awareness and spiritual experiences. The study indicates that nurses can help people with terminal cancer develop coping strategies that allow them to engage in the process of transacting self-preservation. This study also shows that there needs to be more emphasis on spirituality, spiritual issues and the role of spiritual caring in nursing curricula and practice.

Adaptation, Psychological↗

Semantic category interference effects upon the reach-to-grasp movement.

In the present study the kinematics of the reach-to-grasp movement towards a target object in the presence of distractors was investigated. Three experiments were conducted. In the first experiment, there were three conditions, (a) the target alone, (b) the target presented with a distractor object that was semantically similar to the target and (c) the target presented with a distractor object that was semantically different from the target. The same conditions were repeated for the second experiment but the size of the distractors were also manipulated. For the third experiment the target was presented with a distractor object that was semantically different from the target but similar in shape. In the first experiment interference effects were observed in kinematic parameters of the grasp, but not for the reach component when the target and the distractor were semantically different. In the second and the third experiment, similar results were found. Results are discussed in terms of conflicting processing between objects pertaining to different semantic categories.

Adolescent↗

A 42-year-old man with rhabdomyolysis from substance abuse and minor trauma.

During initial assessment and care of this patient, an element of disbelief of the patient's inability to move his extremities was expressed. Manifestation of a severe injury such as that affecting the spinal cord after an extended period of time would be unusual. All other causes of altered motor function should be promptly investigated. The importance of listening and believing the patient was reinforced with this case. Many excellent clinicians will state that 80% of the diagnosis comes from the patient history. The physical examination and diagnostic tests should only validate what has been obtained from listening to the patient. Although we had cared for patients with hyperkalemia in the past, this case expanded our knowledge about a range of therapies available to treat this electrolyte abnormality and the physiologic mechanisms for each. We are impressed with the number of mechanisms and medications that can contribute to the development of rhabdomyolysis. Caregivers are at risk of assuming that the patient's condition fits the category to which they have been triaged. Keeping an open mind concerning the range of rationale for patient signs and symptoms is important.

Adult↗

Digital mammography: comparison of adaptive and nonadaptive CAD methods for mass detection.

RATIONALE AND OBJECTIVES: The authors compared the performance of adaptive and nonadaptive computer-aided diagnostic (CAD) methods for breast mass detection with digital mammography. MATERIALS AND METHODS: Both adaptive and nonadaptive modular CAD methods employed recent advances in multiresolution and mutiorientation wavelet transforms for improved feature extraction. The nonadaptive method uses fixed parameters for the image preprocessing modules. The adaptive method, a new class of algorithms, adapts to image content by selecting parameters for the image preprocessing modules within a parameter range. Comparison of the two methods was performed for each individual CAD module with a region-of-interest (ROI) database containing all mass types and normal tissue. RESULTS: Receiver operating characteristic (ROC) analysis clearly demonstrated an improvement in performance for the three adaptive modules and a significant overall difference between the two methods. The average ROC area index (Az) values were 0.86 and 0.95 for the nonadaptive and adaptive methods, respectively. The corresponding P value is .0145. For a previously reported database of full mammographic images containing 50 abnormal cases with all mass types and 50 normal images, the adaptive CAD method had a sensitivity of 96% (1.71 false-positive results per image) compared with 89% (1.91 false-positive results per image) for the nonadaptive CAD method. CONCLUSION: The adaptive CAD method demonstrated better performance. A study is in progress to determine the generalizability of the adaptive CAD method by applying it to larger retrospective image databases with different film digitizers.

Algorithms↗

Identification of DRB alleles in rhesus monkeys using polymerase chain reaction-sequence-specific primers (PCR-SSP) amplification.

Major histocompatibility complex (MHC) class In molecules play a vital role in the regulation of T-cell functions in the mammalian immune system. Two key features characterize the polymorphism of MHC haplotypes in humans and non-human primates: the existence of a large number of alleles, and the high degree of genetic diversity between those alleles. Rhesus monkeys and Chimpanzees have been extensively used as relevant models for human diseases and transplantation We have investigated DRB genes in 19 macaques, members of 3 families, using polymerase chain reaction with sequence-specific primers (PCR-SSP) and denaturing gradient gel electrophoresis (DGGE). After amplification PCR products were purified and subjected direct sequencing. Seven animals (Madison #1) were typed by DDGE also. We report that the DRB haplotypes defined by PCR-SSP exhibit a high degree of concordance with the data obtained by DGGE and direct sequening. Our data show prominent variability in the number of DRB1 alleles ranging from 1-4 per genotype within these families. This analysis demonstrated that most of the amplicons were identical to Mamu-DRB alleles that our PCR primers were to amplify. However, 98-99% similarity was noticed in the case of Mamu-DRB1*0303, Mamu-DRB6*0103 and Mamu-DRB*W201 alleles. The observed mismatches were located in non-polymorphic regions. Thus, family studies in rhesus macaques performed by molecular methods confirmed the multiplicity of Mamu-DRB1 alleles per haplotype and the existence of allelic associations published earlier. In addition, we propose 3 more DRB allele associations (haplotypes): Mamu-DRB1*04-DRB5*03; Mamu-DRB1*04-*DRB*W5; Mamu-DRB1*04*W2. The proposed medium-resolution PCR-SSP technique appears to be a highly reproducible and discriminatory typing method for detecting polymorphisms of DRB genes in rhesus monkeys.

Alleles↗

GM gene flow.

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Agriculture↗