Biomedical subjects

S Connors

Publications and source records attributed to S Connors.

At least 19 recordsLinked to original sources

PubMed2006

Association of Clinical Cytogeneticists chorion villus sampling database 1987-2000.

OBJECTIVES: To produce a fully searchable Microsoft Access database of mosaic and non-mosaic cytogenetic abnormalities, detected during diagnostic chorionic villi sampling (CVS) to aid laboratories in predicting pregnancy outcome, in particular differentiating between cases of likely genuine fetal cytogenetic abnormalities and those likely to represent confined placental mosaicism (CPM). METHODS: Retrospective collection of referral data, initial karyotype data, follow-up karyotype data and pregnancy outcome data from almost all cytogenetically abnormal diagnostic CVS, processed in UK National Health Service laboratories, between 1987 and 2000. Collection of similar data from a published series of CVS and individual case reports. RESULTS: A fully searchable database of abnormal CVS cases, containing over 5000 entries, has been produced. This is available to download at http://www.ncl.ac.uk/cvs/. CONCLUSIONS: Following detection of a cytogenetic abnormality during prenatal diagnosis using CVS, use of this database allows rapid access to comparable cases from the United Kingdom and the literature. This database will improve the speed of availability and quality of information available to clinicians and patients for pregnancy management and counselling purposes. The database has been designed with future data collection in mind, and can be developed for wider research use, through more detailed registries of individual chromosome abnormalities.

Chorionic Villi Sampling↗

PubMed2000

Urinary basic fibroblast growth factor: a noninvasive marker of progressive cystic renal disease in a child.

Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition with an estimated incidence of 1 in 20,000 live births. Various growth factors have been implicated in the causation of this disease. We describe a child with ARPKD whose levels of urinary basic fibroblast growth factor (bFGF) were markedly elevated. The concentrations of bFGF increased further following right nephrectomy, in response to the compensatory growth of the remaining kidney. We hypothesize that measurement of urinary bFGF may be useful as a noninvasive marker to assess progression of cystic renal development.

Adult↗

PubMed1998

Pigeon fanciers' lung: the mucin antigen is present in pigeon droppings and pigeon bloom.

BACKGROUND: Pigeon intestinal mucin has been implicated as an important antigen pigeon fanciers' lung. This study investigated whether mucin is detectable in pigeon droppings and bloom, the likely antigenic sources in disease. METHODS: Soluble extracts of a number of materials found in a pigeon loft were prepared and specific IgG subclass antibodies to these antigens were measured in 14 antibody-positive pigeon fanciers. Cross-reactivity between these materials and purified pigeon intestinal mucin was investigated by inhibition of anti-mucin ELISA. Mucin was purified from the soluble extracts of these crude antigen mixtures by CsCl density gradient centrifugation. RESULTS: The patterns of IgG subclass responses to purified pigeon intestinal mucin and to the four materials collected from the pigeon loft were similar. Subclass differences between symptomatic and asymptomatic individuals, demonstrable against purified mucin, were similarly seen against pigeon droppings and pigeon bloom. Both pigeon droppings and pigeon bloom were capable of inhibiting IgG binding to purified pigeon mucin, and mucin inhibited substantially the binding of IgG to these materials. Glycoprotein with a density similar to that described for pigeon intestinal mucin was purified from each source. CONCLUSION: Pigeon intestinal mucin is present in a variety of materials found in the environment of the pigeon loft in a form capable of reacting with anti-mucin antibodies in the sera of exposed individuals. Reduction in exposure to these materials may decrease the likelihood of developing pigeon fanciers' lung and minimise reactions in sensitised individuals.

Animals↗

PubMed1998

Basic fibroblast growth factor: a missing link between collagen VII, increased collagenase, and squamous cell carcinoma in recessive dystrophic epidermolysis bullosa.

BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have deficiencies of collagen type VII and have elevated levels of fibroblast collagenase, and a greatly increased risk of cutaneous squamous cell carcinoma. Patients with other genetic blistering disorders do not have elevated collagenase or an increased risk of squamous cell carcinoma, despite chronic wounding. The connection between collagen type VII deficiency, increased collagenase, and squamous cell carcinoma is not understood. MATERIALS AND METHODS: Urine from 81 patients with RDEB (39 patients), junctional epidermolysis bullosa (JEB; 12 patients), and epidermolysis bullosa simplex (EBS; 30 patients), as well as unaffected family members of RDEB patients (33 patients), was tested for the presence of basic fibroblast growth factor (bFGF) using a sensitive radioimmunoassay. These patients included many who were enrolled in the Epidermolysis Bullosa Registry and others who were referred by their physicians. RESULTS: Fifty-one percent of patients with RDEB had elevated levels (> 5000 pg/g) of urinary bFGF. In contrast, none of the patients with JEB had elevated levels of bFGF. Twenty-one percent of clinically unaffected family members had elevated levels of bFGF, and 13% of patients with EBS had elevated levels of bFGF. The frequency of elevated bFGF values among all groups was statistically significant (p = 0.002), and the levels of bFGF in RDEB patients were significantly elevated compared with those of other groups (p < 0.05). CONCLUSIONS: We have found that patients with RDEB have elevated levels of bFGF, which may contribute to increased fibroblast collagenase and the development of squamous cell carcinoma. These results suggest a novel treatment for RDEB, namely, angiogenesis inhibitors, which may antagonize the effects of bFGF in this disorder. There are currently no other means of treatment for this disorder, which has a high morbidity and mortality rate.

Carcinoma, Squamous Cell↗

PubMed1998

Urinary basic fibroblast growth factor. A biochemical marker for preosseous fibroproliferative lesions in patients with fibrodysplasia ossificans progressiva.

Angiogenesis is a prominent histopathologic feature of preosseous fibroproliferative lesions in patients who have fibrodysplasia ossificans progressiva. Basic fibroblast growth factor is an extremely potent in vivo stimulator of angiogenesis, and has been implicated in the growth of solid tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor was performed on urine samples from patients who had active (n = 28) and inactive (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples from normal age and gender matched control subjects (n = 54). Median basic fibroblast growth factor levels were 2705 pg/g of creatinine in the normal control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia ossificans progressiva (no significant difference), and 8793 pg/g of creatinine in patients with active fibrodysplasia ossificans progressiva. Female subjects, both normal and with fibrodysplasia ossificans progressiva, had higher levels of urinary basic fibroblast growth factor than did male subjects. There was no correlation of urinary basic fibroblast growth factor levels with age or severity of preexisting disability. These data document an elevation of urinary basic fibroblast growth factor during acute flareups of fibrodysplasia ossificans progressiva and provide a biochemical basis for considering antiangiogenic therapy for inhibiting endochondral osteogenesis in this disorder.

Adolescent↗

PubMed1997

Elevation of cerebrospinal fluid levels of basic fibroblast growth factor in moyamoya and central nervous system disorders.

Moyamoya syndrome is a vaso-occlusive disease involving the intracranial vessels of the circle of Willis which is accompanied by an intense compensatory recruitment of new vessels. Angiogenic substances such as basic fibroblast growth factor (bFGF) present in the cerebrospinal fluid (CSF) have been proposed as possible mediators of the neovascular response. We analyzed CSF samples collected intraoperatively from predominantly pediatric patients with moyamoya and other conditions such as Chiari malformation (Ch), tethered cord (TC), arteriovenous malformation (AVM), brain tumor (BT) and hydrocephalus (HCP). We found that CSF bFGF was significantly elevated in patients with moyamoya (141 pg/ml, n = 37), Ch (56.7 pg/ml, n = 22), TC (55.1 pg/ml, n = 23), AVM (354 pg/ml, n = 5), and BT (208 pg/ml, n = 5) compared to patients with HCP (5.5 pg/ml, n = 7) and controls (1.6 pg/ml, n = 25; p < 0.05). There was no dependence of CSF bFGF on patient age or gender. Although CSF bFGF in the moyamoya group showed no correlation with the Suzuki radiographic stage at either pre- or post-operative (1-year follow-up) angiography, it showed a trend with the Matsushima angiographic score with increasing collateral vascularization from the synangiosis developing at higher levels of CSF bFGF. Our findings suggest that CSF bFGF may be playing a wide-ranging role in a number of central nervous system conditions associated with ischemia and hypervascularity. Although not a specific marker for moyamoya, elevated CSF bFGF may serve as a weak predictor of the extent of angiogenesis to be expected in indirect revascularization procedures.

Adolescent↗

PubMed1997

Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia.

It has been shown that solid tumors progress in concert with an induction of tumor angiogenesis. It is not known, however, whether a similar phenomenon occurs in leukemia. Angiogenesis was characterized immunohistochemically by factor VIII staining of bone marrow biopsies and quantified by assessment of microvessel density using previously described techniques. We evaluated bone marrow biopsies from 40 children with newly diagnosed, untreated acute lymphoblastic leukemia. In 22 of the patients, we also evaluated angiogenesis after the completion of remission induction chemotherapy. Control specimens were obtained from children undergoing staging evaluations at the time of diagnosis of solid tumors and lymphomas. Microvessels were counted throughout the entire core specimen in consecutive x 200 fields, and a median count per field (cpf) was calculated. In addition, the number of microvessels in the single x 200 field with the highest microvessel density was designated as the "hot spot." Biopsies from children with leukemia and from controls showed median microvessel densities of 42 and 6 counts per field, respectively (P < or = 0.0001). Microvessel density of the hot spots of leukemia specimens and controls were also significantly different, 51 and 8, respectively (P < or = 0.0001). A computer-aided three-dimensional reconstruction model of bone marrow vascularity showed a complex, arborizing branching of microvessels in leukemic specimens compared with single, straight microvessels without branching in controls. Urinary basic fibroblast growth factor, a potent angiogenic factor, was measured in 22 of the children with newly diagnosed leukemia and in 39 normal, age-matched controls. Urinary basic fibroblast growth factor levels were increased in all 22 patients before treatment, were variable during induction chemotherapy, and demonstrated statistically insignificant decreases at the time of complete remission. These findings suggest that leukemia cells induce angiogenesis in the bone marrow and that leukemia might be angiogenesis dependent and raise the possibility for a role of antiangiogenic drugs in the treatment of leukemia.

Antineoplastic Agents↗

PubMed1997

Management of supraventricular tachycardia in the emergency department.

While supraventricular tachycardia is a common condition and seldom leads to serious consequences, it can be challenging to treat. Optimal management requires an accurate diagnosis, especially in the distinction between regular and irregular tachycardias; as well as an understanding of the mechanism responsible for the arrhythmia. In this article, the acute management of supraventricular tachycardias as they present in the emergency department is discussed, based on the underlying electrophysiological principles of arrhythmias.

Anti-Arrhythmia Agents↗

PubMed1996

Medical physics.

Explore the source record for details and available documents.

Biophysics↗

PubMed1996

The Community Medical Alliance: an integrated system of care in Greater Boston for people with severe disability and AIDS.

The Community Medical Alliance in Boston has adapted principles of prepaid managed care to redesign service delivery for people with severe physical disability and with late-stage AIDS. Experience to date suggests that the flexibility of capitation can be used to substantially shift care from its usual hospital focus to clinicians in home and community settings, especially nurse practitioners, with a high degree of patient satisfaction and without apparent compromise in quality. Instead of limiting access, managed care can use prepayment to support early interventions, coordination, and the development of services specifically designed to meet the needs of the target population.

Acquired Immunodeficiency Syndrome↗

PubMed1992

The influence of lung and bone dosimetry on the choice of radiation energy for total body irradiation.

The radiation absorbed dose to lung and bone is of importance for total body irradiation performed prior to bone marrow transplantation for hematologic malignancies. The measurement and calculation of radiation absorbed dose to low density materials such as lung has been discussed in several publications and most total body irradiation procedures account for the increased radiation dose to the lung. However, radiation absorbed dose to bone and soft tissues within bone is not calculated and is assumed to be the same as the dose to soft tissues. Because the bone is different in both density and atomic number from soft tissues, radiation dose calculations are more complex for bone than for lung. As the energy of the radiation beam changes, the dose to heterogeneous tissue varies. This variation of the radiation dose is investigated for radiation beams ranging in energy from 60Cobalt to x-ray beams produced at 18 MV. The radiation absorbed dose to soft tissues within bone is found to increase relative to the dose to soft tissue for higher megavoltage radiations, while at the same time there is a decrease in lung dose. Therefore, since for total body irradiation procedures the target tissues are the soft tissues within bone, a higher dose to those tissues would be an advantage.

Bone and Bones↗

PubMed1992

Conversion of ionization measurements to radiation absorbed dose in non-water density material.

The radiation absorbed dose to non-water equivalent materials of interest in radiotherapy is the dose to lung and the dose to bone. The measurement and calculation of dose to the lung has been of great interest and much effort has gone into the development of accurate lung dose calculation methods. The radiation absorbed dose to the bone is usually not calculated and most absorbed dose calculations have been done without correcting for the presence of bone. For the lower megavoltage photon beams this may be appropriate, however, as the energy of the photon beam increases, the region of electronic disequilibrium becomes larger and pair production which depends on the atomic number of the material becomes significant. Therefore the bone will produce greater perturbations of the dose distribution. The dose to lung-equivalent material is uniquely obtained from ionization measurements. However, in bone-equivalent materials two different calculations of absorbed dose are possible: the absorbed dose to soft tissue plastic (polystyrene) within bone-equivalent material and the dose to the bone-equivalent material itself. Both can be calculated from ionization measurements in phantoms. These two calculations result in significantly different doses in a heterogeneous phantom composed of polystyrene and aluminium (a bone substitute). The dose to a thin slab of polystyrene in aluminium is much higher than the dose to the aluminium itself at the same depth in the aluminium. Monte Carlo calculations confirm that the calculation of dose to polystyrene in aluminium can be accurately carried out using existing dosimetry protocols. However, the conversion of ionization measurements to absorbed dose to high atomic number materials cannot be accurately carried out with existing protocols and appropriate conversion factors need to be determined.

Bone and Bones↗

PubMed1991

The use of an universal wedge for asymmetric fields.

Beam collimators on newer linear accelerators may be collimated asymmetric to the central axis. The asymmetric beam has a non-flat profile adjusted to yield fields whose half widths are not symmetric about the central axis. While some treatment planning systems modify their programs to mimic the nonuniformity, ideally it is preferred to have a flat profile under the open beam. We have developed a universal wedge that can be used to flatten the field for a variety of jaw sizes and positions and energies for the Varian 2100C. The wedge flattens the field to +/- 3% over 80% of the field.

Humans↗

PubMed1990

Cocaine hepatotoxicity in cultured liver slices: a species comparison.

Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse much greater than induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat greater than pig = human.

Adolescent↗

PubMed1988

Development of a translating bed for total body irradiation.

Total body irradiation is used to prepare a patient for bone marrow transplantation. Traditional techniques often sacrifice dose uniformity for patient comfort and ease of treatment. A method has been developed using a translational bed under a Cobalt 60 photon beam. The bed and controller were designed and built on site. A bolused patient lying in the bed is moved at constant speed through the beam. Using this technique, dose homogeneity is optimized by the use of bolus, extended source-skin distance, adequate field size and use of anterior/posterior fields. The dose rate represents a compromise between a value high enough to keep treatment times tolerable by the patient and one that is sufficiently low to avoid treatment complications. The value of 50 cGy/min which was used meets these requirements. Extensive phantom measurements have shown that the dose homogeneity can be obtained to within an acceptable limit of +/- 5%.

Beds↗

PubMed1988

Coregulation of C3-hydroxyl versus C17-hydroxyl glucuronidation of beta-estradiol in pregnancy and after treatment with phenobarbital or ethinyl-estradiol.

The glucuronidation of [3H]estradiol-17 beta at the C3 vs. the C17 hydroxyl groups was determined in female Sprague-Dawley rat liver microsomes. A high-performance liquid chromatography method was developed to resolve the glucuronide conjugates which were then quantitated by liquid scintillation counting. The rates of formation of 17 beta-estradiol 3-(beta-D-glucuronide) (E(2)3G) and 17 beta-estradiol 17-(beta-D-glucuronide) (E(2)17G) were 0.49 +/- 0.03 and 0.40 +/- 0.02 nmol/min/mg of protein, respectively. The apparent Km and Vmax of estradiol glucuronidation were determined in control, pregnant (day 19 of gestation), phenobarbital-treated (80 mg/kg/day i.p. for 5 days) and ethinylestradiol-treated (5 mg/kg/day i.p. for 5 days) female rats. The least-squares estimates of Km and Vmax values as well as the confidence contours of the joint sums of squares for the parameter spaces were calculated. The Vmax (nanomoles per minute per milligram of protein) for E(2)3G was significantly decreased from 0.94 to 0.57 in pregnancy and to 0.47 as a result of ethinylestradiol treatment. The Vmax values for E(2)17G were significantly different in control (0.43), pregnant (0.31) and ethinylestradiol-treated (0.27) rats. Phenobarbital treatment slightly increased the Vmax to 0.51 for E(2)17G whereas the Vmax for E(2)3G was unchanged (0.90) compared to controls. The Km (micromolar) for E(2)3G was 144 in the controls, 112 in pregnancy and 86 and 92 as a result of treatment with ethinylestradiol and phenobarbital, respectively. The Km for E(2)17G was 60 in the controls, 40 in pregnancy, 43 and 68 as a result of ethinylestradiol and phenobarbital treatment, respectively. None of the changes in Km were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

PubMed1985

An all-glass apparatus for liver perfusion of lipophilic substrates. I. Construction and physical characteristics.

An all-glass apparatus for perfusing isolated rat livers was constructed for use in studies of the metabolism by, or action on, the liver of lipophilic substrates. Other designs, which generally include plastic connections or cannulae, can have unnecessarily complicated kinetics because of adsorption of the agent to the plastic parts. Two versions of an all-glass perfusion apparatus are described in detail. Both instruments operate on the same basic principle, but differ in size, total recirculating volume, pump rate, perfusion head pressures, maximum perfusate flow rate, maximum linear velocity in the perfusion head, and oxygenation efficiency. Although the maximum protein handling capacity differs for the two apparatuses, this capacity is so limited that it disallows the use of albumin in the perfusate.

Animals↗

PubMed1979

Children's understanding of monosyllabic nouns in quiet and in noise.

A four-alternative, forced choice adaptive procedure was used to measure the lowest intensity at which children could identify monosyllabic nouns that had been standardized to be understandable (at comfortable listening levels) to inner city, 3-year-old children. Results showed no age-related performance changes when the words were presented against a 12-talker babble or against filtered noise. In quit, however, performance improved between the ages of 5 and 10 years. Performance of children with learning problems was poorer than performance of children achieving normal school progress, even though clinical measures of auditory sensitivity showed no differences. Results are discussed in terms of "semantic closure" skills of children.

Adult↗