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Biomedical subjects

L Sutton

Publications and source records attributed to L Sutton.

At least 37 records · Page 2Linked to original sources

The cholinergic rapid eye movement induction test with arecoline in depression.

The cholinergic rapid eye movement (REM) induction test using arecoline hydrobromide, a cholinergic muscarinic receptor agonist, was studied in patients with affective disorder and in normal controls to determine whether or not depression is associated with enhanced induction of REM sleep by muscarinic agonists. Arecoline induced REM sleep in a dose-dependent fashion in both patients and controls compared with placebo infusions. Compared with normal controls, patients entered REM sleep significantly more rapidly following intravenous administration of 1.0 mg of arecoline hydrobromide than they did following administration of 0.5 mg of arecoline hydrobromide or placebo. These results, as well as those of previous studies, support the hypothesis that patients with affective disorder show a functional supersensitive induction of REM sleep in response to muscarinic receptor agonists and may be consistent with the hypothesis that functional muscarinic receptor "up regulation" is associated with depression.

Arecoline

Properties of plasmids responsible for production of extended-spectrum beta-lactamases.

The extended-spectrum beta-lactamases are believed to arise by mutations which alter the configuration around the active site of TEM- and SHV-type enzymes so as to increase their efficiency with otherwise nonhydrolyzable cephalosporins and monobactams. This hypothesis predicts that the genes for these new enzymes should be found on the same wide variety of plasmids that encode TEM-1, TEM-2, and SHV-1 beta-lactamases and that at least some of them should be mediated by transposons. Fifteen plasmids, each encoding an extended-spectrum beta-lactamase, were examined. Unlike the average TEM plasmid, all were large, ranging in size from 80 to 300 kb. All determined resistance to multiple antimicrobial agents, ranging from 5 to 11, and some conferred resistance to heavy metals and UV radiation as well. The plasmids belonged to a limited number of incompatibility (Inc) groups, including IncC, IncFI, IncHI2, and IncM. Because most of the mutations giving rise to extended-spectrum activity are G.C----A.T transitions and some of the mutant genes have as many as four base substitutions, a plasmid-determined mutator gene was searched for, but no such property was found. Several techniques were used to detect transposition of the extended-spectrum beta-lactamase genes, but a mobile genetic element could not be demonstrated even though eight of the plasmids hybridized with a DNA probe derived from the tnpR gene of Tn3. The genesis of extended-spectrum beta-lactamases may not be as simple as has been supposed.

DNA Transposable Elements

Facial nerve stimulation with cochlear implantation. VA Cooperative Study Group on Cochlear Implantation.

The course of the facial nerve may place it within the current field generated by an activated cochlear implant to produce incidental facial movement. We investigated the presence of facial nerve stimulation associated with cochlear implants in the VA Cooperative Study of Advanced Cochlear implants. Twelve of 82 patients enrolled in this study demonstrated facial nerve stimulation within 2 years of implant activation. Facial nerve stimulation in six patients with multiple channel implants (Nucleus or ineraid devices) either resolved spontaneously (n = 2), or was eliminated by deactivating basal (n = 2) or apical (n = 2) electrodes. Two of six patients with single-channel electrodes (3-M/Vienna devices) demonstrated facial nerve stimulation that resolved spontaneously (n = 2), resolved with lowering current output (n = 2), or was refractory to processor adjustment (n = 2). Intraoperative assessment in one of the refractory cases indicated that facial nerve stimulation resulted from current spread through the modiolus to activate the facial nerve. A variety of factors, including implant design, stimulus parameters, and local tissue impedances, may interact to produce incidental facial stimulation. Low-impedance pathways between the scala tympani and the modiolus may deserve increased recognition as an interactive factor in cochlear implant performance.

Adult

Services and cost of hospitalization for children and adolescents with insulin-dependent diabetes mellitus in New South Wales.

Data on services for Australian children and adolescents with diabetes are limited. The purpose of the present study was to examine the availability, utilization and some of the costs of services for persons of less than 20 years of age with insulin-dependent diabetes mellitus in New South Wales, and to make recommendations for future services. The numbers of prevalent and incident cases of insulin-dependent diabetes mellitus in the zero- to 19-years' age-group in each of the health regions of the State were estimated using data from the insulin-dependent diabetes mellitus register of the Southern Metropolitan Health Region. Information on the available services for young persons with diabetes was obtained from doctors and diabetes educators around the State, and on the utilization of services in the Southern Metropolitan Health Region from interviewing the families of persons whose names are listed in the diabetes register. An estimated range of the annual direct cost of hospital admissions for diabetes in the zero- to 19-years' age-group in New South Wales was calculated by use of the data collected from the diabetes register, the hospital separation data from the NSW Department of Health, the NSW Department of Health estimated bed-day cost and the estimated average cost of a bed day for diabetic patients at The Children's Hospital Camperdown. Services for children and adolescents with insulin-dependent diabetes mellitus in this State are most comprehensive in central Sydney. However, even these excellent services are not utilized fully by the children and their families. The annual cost of hospitalization for diabetes in the zero- to 19-years' age-group in New South Wales is estimated to be approximately +1.5 million. There needs to be an equally high standard of care for all diabetic children in the State; however, the utilization of services, as well as the services themselves, need to be improved and the cost-effectiveness of new services needs to be evaluated.

Adolescent

High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence.

Between April 1986 and March 1989, ten patients under 21 years of age with histologically confirmed malignant astrocytoma, received marrow-ablative chemotherapy with either thiotepa and Etoposide (five patients) or thiotepa, Etoposide and BCNU (five patients), followed by bone marrow 'rescue'. Nine patients had glioblastoma multiforme (GBM), and one patient had an intrinsic brain stem anaplastic astrocytoma (AA). Seven patients were treated for recurrent tumor. Two patients who developed GBM as second malignancies were treated directly following surgical resection. One patient had received irradiation only for recently diagnosed cervical spinal cord GBM. Thiotepa was administered at a total dose of 600-900 mg/M2 over three days, Etoposide was administered at a total dose of 1500 mg/M2 over three days, and BCNU was administered at a total dose of 600 mg/M2 over four days. Non-hematopoietic toxicities have been mainly transient, predictable and acceptable, consisting of oropharyngeal mucositis, cutaneous hyperpigmentation, erythema and desquamation. Four patients achieved complete responses (CR), as determined by radiographic evaluation (CT and/or MRI) on day 28 post-marrow infusion. The mean remission duration of those with CR is 290+ days; two patients presently remain in remission. Two patients achieved partial responses (PR, greater than 50% tumor shrinkage) by day 28 post-marrow infusion; both developed disease progression, at day 61 and 94 post-marrow infusion, respectively. One patient, with a brain stem AA, had stable disease maintained for 13 months post-marrow infusion. With a total (CR + PR) response rate of 60%, these regimens merit evaluation in broader categories of recurrent brain tumor patients, as well as in patients with newly-diagnosed GBM.

Adolescent

Pilocarpine, an orally active muscarinic cholinergic agonist, induces REM sleep and reduces delta sleep in normal volunteers.

The effect of oral pilocarpine, a direct-acting muscarinic, cholinergic agonist, on polygraphic sleep parameters was studied in 13 healthy male volunteers. Subjects received placebo and oral pilocarpine (25 mg) in a double-blind, counterbalanced, crossover design. Pilocarpine shortened the latency of rapid eye movement (REM) sleep and increased total REM time, REM%, and the duration of the first REM period. In addition, it reduced Stage 4 sleep and Delta sleep. Pulse rate was not significantly changed during the first hour of darkness after administration of pilocarpine. Subjective sleep experience and the subjects' condition in the morning were not altered. These results suggest that pilocarpine has central effects (i.e., induction of REM sleep) that are similar to those of other centrally acting muscarinic cholinomimetic agents.

Administration, Oral

Key problems in the management of children with brain tumors.

Steady progress has been made in the clinical management of children with brain tumors. Better diagnostic methods and more efficient surgical, radiotherapeutic, and chemotherapeutic techniques have evolved singly and in various combinations. These advances have at times created problems in patient management; for example, interpretation of clinically inexplicable signal changes on magnetic resonance imaging. Equally substantive, and at a more basic level, is the fact that understanding of the nature of the various tumors remains elusive in many cases. Some lesions seem to behave more like maldevelopments than neoplasms. Specific markers for any of the several tumor types have not been identified. The isochromosome i(17q), found in some malignant pediatric brain tumors, is also present in children with other conditions, both benign and malignant. Fundamental research is hampered by the difficulty in establishing cell lines for even the medulloblastoma, the most common of the frankly malignant group. Until these problems are supervened, important advances will largely remain at the clinical and morphologic level. Close coordination and careful correlation of data among the several members of the pediatric neuro-oncology team is essential for success. Clinical trials of combined modality care especially require well-reasoned rationales and careful definition of objectives, and must include meticulous evaluation of the late effects of therapy in survivors.

Brain Neoplasms

Monoclonal antibody-dependent, cell-mediated cytotoxicity against human malignant gliomas.

Two monoclonal antibodies (MAbs), IgG2a MAb ASHG4 and IgG2b MAb ASHE2, were produced in mice immunized with cultured human malignant glioma cells. Both MAbs bound strongly to the surfaces of long-term cultured glioma cells, and MAb ASHE2 also bound strongly to short-term cultured glioma cells. Sections of frozen glioma tissues bound both MAbs strongly, whereas normal brain tissues showed weaker reactivities, and tissues derived from carcinomas of various histological types were completely unreactive. Furthermore, the MAbs did not bind to peripheral blood cells or bone marrow cells. Although both MAbs bound to the same Mr 27,000-29,000 protein, they may detect different or overlapping epitopes on this antigen. Because MAbs ASHE2 and ASHG4 lysed cultured glioma cells with human peripheral blood lymphocytes as effector cells, they are promising reagents for approaches to immunotherapy of human malignant gliomas.

Antibodies, Monoclonal

The role of radiation therapy in the management of childhood craniopharyngioma.

Between 1965 and 1986, 31 children were treated for craniopharyngioma at the Children's Hospital of Philadelphia. Total removal was attempted in all patients. Some patients received radiation therapy following subtotal removal. Of the patients whose first resection was subtotal, five received radiation and seven did not. Four of the 5 patients who were radiated (80%) are stable (median 89 months, range 42-155 months) and one recurred at 42 months, failed salvage with total removal, and subsequently died of disease. Of the seven who were not irradiated, all had recurrences (median 12 months, range 3-192 months) and one died of disease. Nineteen patients initially had total removal and none received adjuvant radiation. One patient died postoperatively. Of the 18 remaining patients, 6 had recurrences (median 24 months, range 7-100 months) and 12 (66%) are stable (median 42 months, range 9-133 months). One of these stable patients died of endocrine complications 24 months after initial surgery. Fourteen of the 31 patients recurred. Two died with recurrence and one required no further treatment. Eleven had second resections following initial surgical removal. Seven of these 11 went on to receive radiation and four did not. All seven who were radiated are stable (median 33 months, range 1-228 months); whereas 1 of the 4 who were not radiated recurred again at 18 months. This patient had a third resection followed by radiation therapy and is now stable at 20 months. After initial surgery (and before radiation, when given) 26 of 31 patients had panhypopituitarism, 4 had partial deficits, and 1 was normal. Severe diencephalic syndrome, loss of visual acuity, and intellectual deficits were no more frequent in patients treated with total removal, subtotal removal, and in patients who received radiation. We conclude that radiation has an important role following subtotal removal and for salvage treatment after initial surgery. Aggressive attempt at total removal does result in prolonged progression-free survival in some patients. Extensive resections may result in significant mortality and endocrine morbidity. This review suggests that subtotal removal and radiation results in outcomes at least as favorable as treatment with total removal alone.

Adolescent

Pseudomonas cepacia susceptibility to sulbactam.

For 25 of 32 Pseudomonas cepacia isolates, predominantly from sputum of adult patients, agar dilution MICs of sulbactam were 2.5 micrograms/ml, and for only one was the MIC more than 80 micrograms/ml. Susceptibility was reliably predicted by response to a commercial sulbactam-ampicillin disk.

Humans

A digital system for generating dynamic sinusoidal gas concentration signals.

A computer-controlled gas-mixing system is presented. It is capable of mixing four gases, the concentration of three of which will follow a path to be determined by the user. For our purposes the output O2 fraction is maintained constant and the levels of Ar and N2O vary sinusoidally and independently, with periods between 0.25 and 30 min. A fourth gas, N2 is necessary to make the sum of the individual fractions 100%. The system uses banks of between one and four solenoid valves each linked via a sonic choke to a common mixing chamber. A regime of pulse frequency modulation is employed. All calculations and timing of valve switching are performed by a dedicated microcomputer built for the purpose. The device has been used to provide respiratory gas forcing functions for a program of research in respiratory monitoring.

Humans

Performance of a miniaturised O2-Hb dissociation curve analyser on dog's blood.

Oxygen-haemoglobin dissociation curves were determined on dogs' blood using a modified and miniaturised dissociation curve analyser. The Bohr factor describes the way in which pH varies the PO2 corresponding to a particular oxyhaemoglobin concentration. The factor was similar for three saturations and was little affected by whether the pH was changed by changing PCO2, or by adding fixed acid or alkali. The haemoglobin saturations in the mid-range tended to be lower than those predicted by the equation of Rossing and Cain (1966).

Animals

Cells bearing class II MHC antigens in the human placenta and amniochorion.

Immunohistological techniques have been used to study the stromal cells of the human placenta in both the chorionic villous mesenchyme and the connective tissue underlying the amnion. Throughout gestation many of these cells express an antigen (3C10) that is found on mononuclear phagocytes but not on dendritic cells or epidermal Langerhans cells. In the first and second trimesters the placental cells also react with a monoclonal antibody (NA1/34) to the human thymocyte antigen (CD1), a lymphocyte differentiation antigen expressed by cortical thymocytes and Langerhans cells; expression of this antigen diminishes as gestation advances. In contrast, an antibody to a different epitope of CD1 (OKT6) does not bind. Class II MHC antigens are not present in the first trimester but are acquired by increasing numbers of placental macrophages from the second trimester onwards. It is possible that the placenta has significant immune functions and that, by term, placental macrophages may be capable of antigen presentation.

Amnion