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Biomedical subjects

T Martin

Publications and source records attributed to T Martin.

At least 73 records · Page 4Linked to original sources

Analgesic efficacy of orally administered buprenorphine in rats.

The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

Administration, Oral↗

Lung hypoplasia in a patient with del(2)(q33-q35) demonstrated by chromosome microdissection.

We report on a 17-month-old girl with multiple malformations, including lung hypoplasia, multiple ventricular septal defects, craniofacial anomalies, and malrotation of the intestine. Moreover, the patient showed Robin sequence, developmental delay, as well as pre- and postnatal growth retardation. Postnatal cytogenetic analysis revealed an interstitial deletion on the long arm of chromosome 2. Microdissection and reverse chromosome painting of the aberrant chromosome 2 as well as FISH with a panel of chromosome 2q band-specific YACs mapped the deletion to 2q33-q35. Lung hypoplasia has not been described so far in patients with del(2)(q33-q35). A review of previously reported patients showed variable phenotypes apparently due to different deleted chromosomal segments.

Abnormalities, Multiple↗

Investigation of the prevalence of Legionella species in domestic hot water systems.

AIMS: To investigate the prevalence of Legionella spp. in the hot water systems of a representative sample of Wellington domestic residences with electrically heated hot water systems, and to investigate risk factors (eg water temperature, plumbing materials) for such contamination. METHOD: 100 households with electrically heated hot water systems in the Wellington area were investigated. Samples of hot water from several hot water outlets were collected, and characteristics of the plumbing system were recorded. Water samples and swabs were cultured and further examined by polymerase chain reaction (PCR) and direct fluorescence antibody (DFA) testing to identify Legionella spp. and serogroups. RESULTS: No Legionella spp. were isolated by culture. PCR tested positive for Legionella in specimens from twelve residences. Six of these were also positive by DFA testing. The only environmental factor found to be associated with the presence of Legionella was recent plumbing work on the hot water system. Five of the twelve PCR-positive residences, and four of the six DFA-confirmed residences had hot water delivery temperatures in excess of 60 degrees C. CONCLUSIONS: The results suggest that either Legionellae colonise domestic hot water reticulation systems and/or that the organisms are killed during passage through the hot water tank. Both possibilities may be correct. Further work to characterise the microbial ecology of Legionella-positive hot water distribution systems would be useful, as would the development of improved methods for culturing the organisms from potable water.

Humans↗

Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells.

OBJECTIVE: Patients with Sjögren's syndrome (SS) have an increased risk of developing monoclonal B cell non-Hodgkin's lymphomas (MNHL), which frequently occur in the salivary glands (SG). The transition from the benign lymphocyte infiltrate of the gland that characterizes SS to MNHL is not well understood. Previous sequence analyses of the expressed variable (V) region genes have supported the theory that the surface Ig (sIg) plays an important role in the initial expansion of nonmalignant B cell clones and in lymphomagenesis. However, the antigenic specificities of these B cells were unknown. We describe the specificities of the Ig expressed by 2 cases of MNHL that developed in the SG of 2 patients with SS. METHODS: The expressed V genes were amplified by polymerase chain reaction from biopsy specimens, sequenced, and subcloned into eukaryotic expression vectors. The constructs were transfected into P3X63-Ag8.653 cells to obtain 2 monoclonal cell lines, each secreting 1 of the sIg expressed by the MNHL. These IgM were tested by enzyme-linked immunosorbent assay and immunofluorescence against a panel of antigens potentially implicated in SS. RESULTS: Our main finding was that the Ig products of the neoplastic B cells were rheumatoid factors (RF). Contrary to expectations, they did not react with nuclear or cytoplasmic antigens, double-stranded DNA, self antigens commonly bound by natural autoantibodies, or SG tissue. CONCLUSION: Previous analyses of V gene use have provided indirect evidence that SG MNHL may frequently express RF. We demonstrate that this hypothesis is true in the 2 patients we studied. Large-scale studies will be needed to establish the exact frequency of RF specificity among SS-associated MNHL.

Aged↗

Cytotoxic T lymphocyte antigen 4 (CD152) regulates self-reactive T cells in BALB/c but not in the autoimmune NOD mouse.

Recent studies demonstrated that engagement of cytotoxic T lymphocyte antigen 4 (CTLA-4)/(CD152) generates an inhibitory signal to T cells which arrests an on-going immune response. Since aberrant CD152 activity is thought to contribute to autoimmunity, we examined the effect of CD152-mediated inhibitory signals on the response to self and foreign antigens in autoimmune, diabetes-prone NOD and non-autoimmune BALB/c mice. The interaction of CD152 with its ligand B7 was prevented by treating the mice with anti-CD152 blocking antibody, before and following immunization of the mice with the self-antigen, syngeneic islet cells, or the foreign antigen, key-hole limpet hemocyanin (KLH). CD152 blockade in BALB/c mice stimulated a robust islet-specific T cell-mediated immune response compared to control antibody-treated mice. The augmentation of T cell responses in BALB/c mice was consistent with the role proposed for CD152 as a down-regulator of T cell activation responses. Furthermore, CD152 blockade unmasked islet cell specific autoreactive T cells in the non-autoimmune BALB/c mouse. Conversely, CD152 blockade in NOD mice failed to regulate islet-specific auto-reactive T cell responses. However, CD152 blockade enhanced the T cell response to the exogenous, foreign antigen KLH in both non-autoimmune BALB/c and autoimmune NOD mice. Collectively, these results suggest that there is not a global defect in CD152-mediated regulation of peripheral T cell immune responses in NOD autoimmune mice but rather, a defect specific to T cells recognizing self antigen.

Abatacept↗

3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results.

BACKGROUND: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. PATIENTS AND METHODS: Between January 1997 and August 1998 we treated 35 patients with stage cT1-3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning ("Offenbach system") was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. RESULTS: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. CONCLUSIONS: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well-tolerated and effective treatment in the short-time follow-up of median 18 months.

Adenocarcinoma↗

Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants.

OBJECTIVE: To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN: Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING: Ambulatory-care facilities of the participating centers. SUBJECTS: 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION: Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES: Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED: Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS: One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS: This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.

Anthropometry↗

Navigation system for interstitial brachytherapy.

PURPOSE: To develop a computed tomography (CT) based electromagnetic navigation system for interstitial brachytherapy. This is especially designed for situations when needles have to be positioned adjacent to or within critical anatomical structures. In such instances interactive 3D visualisation of the needle positions is essential. METHODS AND MATERIALS: The material consisted of a Polhemus electromagnetic 3D digitizer, a Pentium 200 MHz laptop and a voice recognition for continuous speech. In addition, we developed an external reference system constructed of Perspex which could be positioned above the tumour region and attached to the patient using a non-invasive fixation method. A specially designed needle holder and patient bed were also developed. Measurements were made on a series of phantoms in order to study the efficacy and accuracy of the navigation system. RESULTS: The mean navigation accuracy of positioning the 20.0 cm length metallic needles within the phantoms was in the range 2.0-4.1 mm with a maximum of 5.4 mm. This is an improvement on the accuracy of a CT-guided technique which was in the range 6.1-11.3 mm with a maximum of 19.4 mm. The mean reconstruction accuracy of the implant geometry was 3.2 mm within a non-ferromagnetic environment. We found that although the needles were metallic this did not have a significant influence. We also found for our experimental setups that the CT table and operation table non-ferromagnetic parts had no significant influence on the navigation accuracy. CONCLUSIONS: This navigation system will be a very useful clinical tool for interstitial brachytherapy applications, particularly when critical structures have to be avoided. It also should provide a significant improvement on our existing technique.

Brachytherapy↗

Evaluation of the BACTEC MGIT 960 system for the recovery of mycobacteria.

We evaluated the BACTEC MGIT 960 system, which is a fully automated, non-invasive, continuous monitoring system for the growth and detection of mycobacteria. Including respiratory and other specimens, 1,742 specimens were processed and inoculated into the BACTEC MGIT 960 and the BACTEC 460 TB Systems, as well as onto Lowenstein-Jensen (L-J) media. A total of 104 isolates of mycobacteria were recovered from all culture systems. This included Mycobacterium tuberculosis complex, Mycobacterium avium-intracellulare (MAI) complex and other mycobacteria (MOTT). The isolation rates for M. tuberculosis complex and MAI complex were comparable for the BACTEC 460 (54.8% and 13.5%) and the BACTEC MGIT 960 (51.9% and 13.5%). The overall isolation rate was less for BACTEC MGIT 960 (76.9%) which was due to lesser number of MOTT isolates recovered from this system. The mean times to detection (TTD) for all mycobacteria were 9.3 days for the BACTEC MGIT, 14.6 days for the BACTEC 460 and 21.6 days for L-J. A significant difference was observed when TTD was tested in relation to degree of positivity in smears, with the BACTEC MGIT maintaining the short TTD even with less number of bacilli in the smear. The contamination rates were, 6.4% for BACTEC MGIT, 2.9% for BACTEC 460 and 12.1% for L-J medium. The BACTEC MGIT 960 system shows performances comparable to the BACTEC 460 and seems to be a dependable, user friendly system.

Culture Media↗

Subsets of macrophages and dendritic cells in nonobese diabetic mouse pancreatic inflammatory infiltrates: correlation with the development of diabetes.

Islet-specific T cells are essential in the development of type I diabetes. The role of non-lymphoid cells is relatively unclear, although infiltration of dendritic cells and macrophages is the first sign of islet autoimmunity in diabetes-prone nonobese diabetic (NOD) mice. BDC2.5 is one of the autoreactive T cell clones isolated from NOD mice. Transfer of BDC2.5 T cells into young NOD mice accelerates diabetes development, whereas transgenic expression of the BDC2.5 T cell receptor on NOD T cells (BDC2.5 TCR-Tg NOD) markedly reduces diabetes development. We show that, although the same antigen-specificity is involved, both models differ significantly in insulitis. BDC2.5 TCR-Tg NOD mice develop an extensive, but non-aggressive, peri-insulitis by 3 weeks of age. In these large peri-islet infiltrates, resembling secondary lymphoid tissue, BM8+ macrophages (Mphi) are virtually absent. In contrast, BDC2.5 T cell clone transfer results in an aggressive insulitis with small infiltrates, but relatively large numbers of BM8 Mphi. Infiltration of BM8+ Mphi therefore correlates with islet destruction. This is, however, not observed for all Mphi; Monts-4+ Mphi follow a reverse pattern and are present in higher numbers in BDC2.5 TCR-Tg than in transferred mice. ER-MP23+ Mphi are reduced in both transferred and transgenic mice compared with wild-type NOD. Thus, this study underlines and extends previous data suggesting that Mphi are implicated in both early and late phases in diabetes development. Furthermore, our data imply that subsets of non-lymphoid cells have different roles in diabetes development. It is, therefore, important to recognize this heterogeneity when interpreting both in vivo and in vitro studies concerning non-lymphoid cells in diabetes.

Animals↗

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding.

The aim of this study was to test the effectiveness of isosorbide-5-mononitrate (IM) as an adjunct to propranolol (PR) in the prevention of variceal rebleeding. Ninety-five cirrhotic patients with variceal bleeding were randomly assigned to treatment with PR + IM (46 patients) or PR alone (49 patients). Eighteen patients in the PR + IM group and 28 in the PR group had rebleeding during the 2 years after randomization. The actuarial probability of rebleeding 2 years after randomization was lower in the PR + IM group (40.4% vs. 57.4%) but the difference was not significant (P =. 09). However, the decrease in the risk of rebleeding reached statistical significance after stratification according to age, i.e. less than 50 versus >/=50 years old, (P =.03) or by adding an additional year of follow-up (P =.05). No significant difference was found in rebleeding index and survival. The multivariate Cox analysis indicated first, that both treatment (P =.03) and age (P =. 001) were factors predictive of rebleeding and second, that PR + MI reduced the risk of rebleeding by half (relative risk: 0.51, 95% confidence interval: 0.28-0.95). Seven patients in the PR + MI group and 1 patient in the PR group had to discontinue one of the drugs because of adverse events (P =.03). These results suggest that the addition of IM improves the efficacy of PR alone in the prevention of variceal rebleeding in cirrhotic patients. However no beneficial effects were observed on other parameters reflecting the efficacy of treatment.

Adrenergic beta-Antagonists↗

Mechanical and histologic evaluation of Collagraft in an ovine lumbar fusion model.

The purpose of this study was to determine the effectiveness of a composite material composed of Type I bovine dermal collagen, 65% hydroxyapatite, and 35% tricalcium phosphate ceramic (Collagraft Bone Graft Matrix Strip NeuColl Incorporated, Palo Alto, CA) as a bone graft substitute for spinal fusion with and without the use of autologous bone marrow in an ovine lumbar spine model with pedicle screw fixation. Twenty-four adult sheep underwent a single level posterolateral (intertransverse process) L3-L4 lumbar fusion with one of three graft materials combined with rigid pedicle screw fixation. The three graft materials were Collagraft, Collagraft with marrow, and autogenous corticocancellous bone graft. Animals were euthanized 6 months after surgery and evaluated using dual energy x-ray absorptiometry, radiographs, histologic analysis, and mechanical testing. Dual energy xray absorptiometry between the transverse processes revealed that the mineral densities for the two Collagraft groups were significantly higher than the autogenous bone graft group. Histologic analysis confirmed that Collagraft was highly compatible and was well incorporated into the fusion mass. Both Collagraft groups had thick trabeculae and a mixture of lamellar and plexiform bone. The autogenous bone graft group had a smaller fusion complex, composed primarily of lamellar bone with thinner and fewer trabeculae. All three groups had similar mechanical properties. These results support the use of Collagraft in spinal fusion with pedicle screw fixation.

Absorptiometry, Photon↗

Dynamic fracture in a discrete model of a brittle elastic solid

Dynamic fracture of brittle materials is studied by means of a molecular dynamics simulation of a two-dimensional (2D) lattice of point particles. By a particular discretization of the continuum equations of elasticity, we derive the Born model in such a way that the model parameters are related to the material properties. Numerical simulations are performed, which show a branching instability, under Mode I loading, occurring at a critical crack tip speed. The analysis of the dynamical stress tensor field near the tip shows a qualitative similarity to Yoffe's stress field.

Journal Article↗

Alterations of Alzheimer's disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations.

We determined the levels of endothelial inflammation using MECA-32 antibody and alpha 4 nicotinic receptor subunit densities employing [3H]epibatidine binding in the brains of Alzheimer's disease (AD) patients, cholesterol-fed rabbits, and appropriate controls. We also assessed rabbit brain for beta-amyloid levels and immunohistochemical localization, and for evidence of blood-brain barrier breach using normally-excluded Evans Blue dye. Dietary cholesterol induced a twofold increase in beta-amyloid concentration in rabbit hippocampal cortex, which may be related to the appearance of beta-amyloid immunoreactivity in the neuropil. Epibatidine binding was significantly decreased in AD superior frontal cortex, but unchanged in the superior frontal cortex of cholesterol-fed rabbits. Increased vascular MECA-32 immunoreactivity occurred in AD and cholesterol-fed rabbit brain. Evans Blue dye could be found in the parenchyma of cholesterol-fed rabbits only, and appeared as pockets of dye surrounding small blood vessels. The data suggest that vascular inflammation can lead to breach of the blood-brain barrier, which may produce biochemical derangements in surrounding brain tissue that are conducive to production of beta-amyloid.

Aged↗

A technique for isolated arthrodesis for inflammatory arthritis of the talonavicular joint.

There are few reports in the literature documenting the efficacy of isolated arthrodesis for inflammatory arthritis of the talonavicular joint. Accordingly, we reviewed a single surgeon's experience with this procedure in twenty consecutive cases from this patient population. A technique using indirect joint distraction and the combined use of screw and staple fixation was employed. Solid arthrodesis was noted radiographically in 19 of 20 feet (95%) at an average of 11 weeks. Complications included one non-union, one deep venous thrombosis, and one superficial wound infection. Objective results were graded as excellent in 16 cases, good in 3 cases, and poor in one case. Subjectively, 18 patients were satisfied and one patient dissatisfied with the results of the procedure. It is concluded that isolated arthrodesis is an effective procedure for the treatment of inflammatory arthritis of the talonavicular joint, offering significant pain relief and improved function. Additionally, the use of indirect joint distraction and fixation with screws and staples is a reliable technique associated with an excellent fusion rate.

Adult↗

Humboldt penguins outmanoeuvring El Niño.

We satellite-tracked five Humboldt penguins during the strong 1997/98 El Niño Southern Oscillation (ENSO) from their breeding island Pan de Azúcar (26 degrees 09'S, 70 degrees 40'W) in Northern Chile and related their activities at sea to satellite-derived information on sea surface temperature (SST), sea surface temperature anomaly (SSTA), wind direction and speed, chlorophyll a concentrations and statistical data on fishery landings. We found that Humboldt penguins migrated by up to 895 km as marine productivity decreased. The total daily dive duration was highly correlated with SSTA, ranging from 3.1 to 12.5 h when the water was at its warmest (+4 degrees C). Birds travelled between 2 and 116 km every day, travelling further when SSTA was highest. Diving depths (maximum 54 m), however, were not increased with respect to previous years. Two penguins migrated south and, independently of each other, located an area of high chlorophyll a concentration 150 km off the coast. Humboldt penguins seem to use day length, temperature gradients, wind direction and olfaction to adapt to changing environmental conditions and to find suitable feeding grounds. This makes Humboldt penguins biological in situ detectors of highly productive marine areas, with a potential use in the verification of trends detected by remote sensors on board satellites.

Acclimatization↗

[Radiotherapy in Langerhans-cell histiocytosis. 2 case reports and review of the literature].

The use of radiotherapy in the treatment of Langerhans' cell histiocytosis was first reported in the literature in 1930 and has been proven as effective in numerous studies. We present the results of two female adults with eosinophilic granuloma of bone who underwent conventionally fractionated radiation therapy with total doses of 7 x 1.8 Gy and 7 x 2.0 Gy in four different sites. After observation periods raging from three months to six years local control of the disease was achieved in all treated locations. A review of 18 previously published studies include a total of 310 sites of eosinophilic granuloma of bone in 216 patients. It was demonstrated in 13 studies that the patients had complete relief of symptoms. An average of 94.3% had local control of the symptoms. Furthermore, in 12 studies for a total of 344 cases with involvement of other organs local control was reported in an average of 64.8% (range: 14.3-100%). Based on our own observations and on the literature review we conclude that low dose radiation therapy plays an important role in the management of localised Langerhans' cell histiocytosis. In order to minimise the risk of radiation induced neoplasms an accurate and precise radiation technique is required.

Adult↗