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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 37 records · Page 2Linked to original sources

Using data from the 1991 census.

The 1991 census for England and Wales provides a substantial amount of data on demography, ethnicity, housing tenure, employment status, and other social factors for geographical areas ranging in size from enumeration districts upwards. Many in the health service and in the academic community are making use of the data in the 1991 census. However, users of census data need to be aware of the problems and limitations of these data, which include the format of the data, data modification and suppression, sampling error, and underenumeration. An important innovation of the 1991 census was that the census form included a question on the postcode of respondents; this allowed the Office of Population Censuses and Surveys to produce a postcode-enumeration district look up table which overcomes many of the problems previously encountered in trying to assign postcodes to enumeration districts. The new look up table also includes the grid reference of postcodes, and this will improve the geographical referencing of census data.

Data Collection

Position-dependent variegation of globin transgene expression in mice.

Expression of genes in eukaryotes has commonly been analyzed in a whole tissue, and levels of expression have been interpreted as the result of equivalent rates of transcription in every cell. We have produced transgenic mouse lines that express beta-galactosidase under the control of globin promoters linked to the major tissue-specific regulatory element of the alpha-globin locus, which permits the analysis of transgene expression in individual red blood cells. We find that expression of the transgene within all mouse lines is heterocellular. Individual cells either do not express the transgene at all or express it at a level characteristic of that line. The number of beta-galactosidase-expressing cells varies greatly between different lines of transgenic mice at any defined stage of development, but within a transgenic line, individual mice have strikingly similar numbers of expressing cells. This suggests that the degree of heterocellular expression is determined by the site of integration, as is seen in position-effect variegation.

Animals

Craniosynostosis and kidney malformation in a case of Hennekam syndrome.

Hennekam syndrome is a rare autosomal recessive syndrome which was described for the first time in 1989. Here, we present a girl with intestinal lymphangiectasia, severe lymphedema of limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this syndrome. While the molecular basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its variable clinical expression.

Craniosynostoses

Genomic mapping by end-characterized random clones: a mathematical analysis.

Physical maps can be constructed by "fingerprinting" a large number of random clones and inferring overlap between clones when the fingerprints are sufficiently similar. E. Lander and M. Waterman (Genomics 2: 231-239, 1988) gave a mathematical analysis of such mapping strategies. The analysis is useful for comparing various fingerprinting methods. Recently it has been proposed that ends of clones rather than the entire clone be fingerprinted or characterized. Such fingerprints, which include sequenced clone ends, require a mathematical analysis deeper than that of Lander-Waterman. This paper studies clone islands, which can include uncharacterized regions, and also the islands that are formed entirely from the ends of clones.

Chromosome Mapping

Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication.

Interleukin-1 beta (IL-1 beta), a cytokine released by activated immune cells, elicits various illness symptoms including hyperthermia. Previous hypotheses to account for these actions have focused on blood-borne IL-1 beta exerting its effects directly at the level of the brain. However, recent behavioral and physiological evidence suggest that IL-1 beta can activate the subdiaphragmatic vagus. The present experiments demonstrate that subdiaphragmatic vagal transection disrupts the hyperthermia-inducing effects of recombinant human IL-1 beta and stress. These data provide evidence for a novel route of immune-brain communication, as well as a novel route whereby stress can influence physiological processes.

Animals

Preparation of a macroporous biodegradable polylactide implant for neuronal transplantation.

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an original method consisting of the aggregation of calibrated poly-D,L-lactide microparticles. The size of the interstices between the aggregated microspheres was in a direct relationship to the microsphere diameter. A first approach was based on coating the microspheres with poly(vinyl alcohol) followed by chemically crosslinking the coating layers that were in mutual contact. This method was disregarded because of the acute cytotoxicity of glutaraldehyde used as the crosslinking agent, the absence of macroporosity, and the complete lack of flexibility. A physical technique of aggregation was then tested, which relied on the plasticization of poly-D,L-lactide microspheres with triethylcitrate to the point where microspheres strongly adhered to each other when they were in contact. This method has proved to be straightforward and definitely superior to the chemical approach, particularly with respect to cytotoxicity, control of macroporosity, and flexibility. A polymer support was thus successfully which was biodegradable, macroporous( interconnected pores of 10-100 microns in diameter), and flexible. This potential medical device is presently being used for neuronal transplantation in the central nervous system.

Animals

MR geometric distortion correction for improved frame-based stereotaxic target localization accuracy.

We present a method to correct the geometric distortion caused by field inhomogeneity in MR images of patients wearing MR-compatible stereotaxic frames. Our previously published distortion correction method derives patient-dependent error maps by computing the phase-difference of 3D images acquired at different TEs. The time difference (delta TE = 4.9 ms at 1.5 T) is chosen such that the water and fat signals are in phase. However, delta TE is long enough to permit phase wraps in the difference images for frequency offsets greater than 205 Hz. Phase unwrapping techniques resolve these only for connected structures; therefore, the phase difference for fiducial rods may be off by multiples of 2 pi relative to the head. We remove this uncertainty by using an additional single 2D phase-different image with delta TE = 1 ms (during which time no phase-wraps are typically expected) to determine the correct multiple of 2 pi for each rod. We tested our method in a cadaver and in a patient using CT as the gold standard. Targets in the frame coordinates were chosen from CT and compared with their locations in MR. Localizing errors using MR compared with CT were as large as 3.7 mm before correction and were reduced to less than 1.11 mm after correction.

Artifacts

Late thalamic atrophy in infarction of the middle cerebral artery territory in neonates. A prospective clinical and radiological study in four children.

We report four cases of progressive thalamic atrophy following ipsilateral cerebral infarction in the territory of the middle cerebral artery in neonates, with prospective radiological and clinical follow-up. This type of atrophy appears within 6 months after the onset of cerebral infarction. In the short term, this atrophy has no action on sensory and memory function and/or on sensory evoked potentials. This atrophy is not the result of secondary ischemic neuronal damage. Judging from several other experimental studies, thalamic atrophy may primarily result from retrograde degeneration. It would be interesting to observe the consequences of this atrophy on sensory and memory function over a long period.

Cerebral Arteries

Inhibition of tumor necrosis factor is protective against neurologic dysfunction after active immunization of Lewis rats with myelin basic protein.

Increasing evidence indicates that the cytokines, tumor necrosis factor (TNF), interleukin-1, and/or interferon-gamma, may play a crucial role in the pathogenesis of multiple sclerosis. Several reports demonstrated that inhibition of TNF is highly protective in experimental allergic encephalomyelitis (EAE) when sensitization is accomplished by the passive transfer of myelin basic protein (MBP) sensitized lymphocytes. However, successful protection has not been reported in EAE that is induced by active immunization with MBP. We examined the effects of a TNF inhibitor, dimeric polyethylene glycol linked form of the type I soluble receptor of TNF, PEG-(rsTNF-RI)2, on actively acquired EAE. Treatment with PEG-(rsTNF-RI)2 at 0.3-3 mg/kg every other day or every third day starting on Day 9 postimmunization with MBP during the effector phase of EAE significantly inhibited clinical signs in a dose-dependent manner. Histological examination of the central nervous system indicated that the administration of PEG-(rsTNF-RI)2 reduced, in part, the cellular infiltrate, particularly in the lumbar and sacral regions of the spinal cord. These studies suggest that TNF is a pivotal mediator of the inflammation resulting from the complete immune response induced by active immunization with MBP.

Animals

Effects of alfuzosin on urethral and blood pressures in conscious male rats.

This study was undertaken to determine simultaneously the effects of alfuzosin on urethral and blood pressures in the same conscious male rat. Alfuzosin (i.v., 3, 10 and 30 micrograms/kg) dose-dependently decreased urethral pressure without affecting mean arterial blood pressure. At the higher dose, blood pressure was only slightly and transiently decreased while a marked decrease (-40%) in urethral pressure was observed. Therefore, this experimental model is suitable to assess uroselectivity.

Adrenergic alpha-1 Receptor Antagonists

Evidence that secretory products of the reticuloepithelial cells of the rat thymus modulate the secretion of gonadotrophins by rat pituitary cells in culture.

It is now well accepted that the endocrine system can be strongly influenced by the immunological status of the body. This laboratory has provided documented evidence that the rat thymus produces a biologically active secretion, with a molecular weight of approximately 30 kDa, that augments the gonadotrophin-releasing hormone (GnRH) stimulated secretion of gonadotrophins by isolated pituitary cells in culture. To determine the cells of origin of the factor involved, the reticulo-epithelial cells from the thymus were incubated in vitro to provide media for the examination of possible effects on the secretion of gonadotrophins by the rat pituitary. The enrichment of the culture with reticulo-epithelial cells was confirmed using anticytokeratins antibodies. It was found that the addition of such conditioned medium increased the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), with a greater effect on the former. The increment in gonadotrophin secretion was time- and dose-dependent. This same conditioned medium also potentiated the effect of GnRH on the cultured pituitary cells. The fractionation of thymic-conditioned medium using selective molecular membrane filters, provided evidence that the active factor or factors involved in the enhanced secretion of gonadotrophins are larger than 10 kDa MW. Present findings show that thymic reticulo-epithelial cells are responsible for this activity.

Animals

Protective effect of the interleukin-1 receptor antagonist (IL-1ra) on experimental allergic encephalomyelitis in rats.

Cytokines such as interleukin-1 (IL-1) are thought to contribute to the inflammatory response associated with autoimmune diseases like multiple sclerosis. We assessed the role of IL-1 in an animal model of MS, experimental allergic encephalomyelitis (EAE), by testing the effects of treatment with an IL-1 receptor antagonist (recombinant human IL-1ra) on the clinical course of EAE in Lewis rats. Treatment with rhIL-1ra every day starting on Day 9 post-immunization with myelin basic protein (MBP) during the effector phase of EAE significantly inhibited clinical signs of EAE. rhIL-1ra delayed the onset, reduced the severity of paralysis and weight loss, and shortened the duration of disease. These data suggest that IL-1 is a mediator of the inflammation resulting from active immunization with MBP, and that inhibitors of IL-1 may prove beneficial for the treatment of autoimmune or inflammatory diseases of the central nervous system.

Animals

Selective use of the duplex scan in diagnosis of deep venous thrombosis.

BACKGROUND: The introduction of managed care, with its emphasis on cost containment, makes it of paramount importance that all tests ordered be specific, selective, and appropriate. METHOD: The data concerning patients who underwent a duplex scan to determine the presence of deep venous thrombosis (DVT) over a 68-month period, were reviewed in order to determine if the test was ordered appropriately. The symptoms that prompted the test, type of physician ordering the test, and demographic data for both the patients who tested positive and negative were tabulated. RESULTS: A total of 2,841 duplex scans were ordered over a 68-month period for presumptive diagnosis of DVT of an extremity. A total of 524 (18%) scans were positive for thrombosis; however, 27% (144) of these were superficial or a small isolated thrombus in the calf or forearm. Thus, only 380 studies, or 13% of the total scans ordered, were positive for a major DVT requiring treatment. The only symptoms consistently found in the positive group were pain, edema, dyspnea, and a history of DVT. Of the types of physicians ordering the test, emergency department physicians were least specific, with only 12% of the scans ordered being positive for DVT; surgeons were more selective and had a 19% positive rate, while internal medicine physicians had a 20% positive rate. CONCLUSION: The duplex scan allows the physician the ability to easily diagnose venous thrombosis, but its indications need to be more carefully guided by history, physical examination, risk factors, and logic to enhance its use and effectiveness. This study analyzes the risk factors and symptoms involved in order to assist the clinician in determining when the duplex scan is indicated.

Adolescent

The effects of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transmyocardial impedance. Implications for implantable cardioverter-defibrillator implantation.

The influence of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transcardiac impedance is not well characterized. However, this relationship is of clinical importance during automatic defibrillator implantation done with concomitant cardiac surgery, and there is anecdotal information that criteria for successful implantation are harder to achieve after such operations. We studied the effect of controlled hypothermia on defibrillation energy requirements and transcardiac impedance in a canine model of cardiopulmonary bypass in which 26 animals underwent right atrial and femoral arterial cannulation, as well as continuous hemodynamic and intramyocardial temperature monitoring. The defibrillation energy requirements were evaluated at 60-minute intervals with an epicardial patch system, and transcardiac impedance was measured before and after the multiple inductions and terminations of ventricular fibrillation. In group 1 (n = 10) defibrillation energy requirements were evaluated immediately after initiation of cardiopulmonary bypass at 37 degrees C (T0), after gradual cooling to 28 degrees C (T1), and after rewarming to 37 degrees C (T2). Group 2 (n = 16) comprised time controls that were identically instrumented and studied, but maintained at 37 degrees C throughout. Percent successful defibrillation was plotted against delivered energy, and the raw data fit by logistic regression. The energy at which 50% of shocks were successful (E50) was 3.23 +/- 0.89 joules at T0, 5.12 +/- 1.85 joules at T1, and 4.42 +/- 1.22 joules at T2 in group 1; this was not significantly different from the corresponding group 2 E50 values, which were 3.11 +/- 1.39 joules, 4.95 +/- 2.47 joules, and 5.59 +/- 3.18 joules, respectively. Both groups demonstrated a significant increase in E50 during the first hour of cardiopulmonary bypass (mean increase from T0 to T1 was 1.89 joules in group 1 and 1.84 joules in group 2, p < 0.05). Transmyocardial impedance fell progressively during the group 2 experiments from 73.6 +/- 12.9 omega at the beginning of the T0 shock series to 61.4 +/- 8.9 omega at the end of the T2 shock series. A similar reduction in transmyocardial impedance was observed during the course of all the group 1 experiments; however, at the beginning of the T1 shock series impedance was significantly elevated to 77.4 +/- 12.3 omega (p < 0.05 compared with group 2 and with end T0 in group 1). There was no relationship between defibrillation energy requirements and transcardiac impedance; there was also no correlation between either of these parameters and intramyocardial extracellular pH or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Pathologic voice type and the acoustic prediction of severity.

We hypothesized that acoustic measures would predict dysphonic severity with differential results for pathological voice types. An instructional program based upon synthesized voice signals was developed to facilitate an awareness of prototypical voice types. Eighty phonatory samples representing normal subjects as well as patients with unilateral vocal fold paralysis, vocal nodules, and functional dysphonia were analyzed acoustically on the basis of four measures: average fundamental frequency (F0), jitter, shimmer, and harmonic/noise ratio (H/N ratio). Following training, 29 listeners classified 62% of the phonatory samples on the basis of breathy, hoarse, rough, and normal. Dysphonic severity of rough voices was predicted more successfully by H/N ratio (r2 = .73) than by shimmer (r2 = .43). Dysphonic severity of breathy voices was predicted only by the combined features of less jitter, more shimmer, and lower H/N ratio (r2 = .74). No combination of acoustic variables was successful in the prediction of the hoarse voice type.

Adolescent