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Biomedical subjects

D M Simpson

Publications and source records attributed to D M Simpson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Surgical versus non-surgical treatment and recurrent periodontal disease in beagle dogs.

The present study was designed to compare clinical, microbiologic and histometric parameters of recurrent periodontal disease in areas which had been treated either surgically (SU) or nonsurgically (NS). Periodontal disease was induced for 6 months in 3 quadrants in each of 6 beagle dogs. 2 of the 3 diseased quadrants were treated by definitive surgical or nonsurgical therapy followed by plaque control for 4 months. 2 dogs were then sacrificed to provide histometric data. Periodontal disease was reinduced in the remaining 4 dogs by allowing plaque accumulation for 6 months after which the dogs were sacrificed for histometric analysis. Clinical parameters were recorded and darkfield microscopic analysis of subgingival plaque samples was performed at regular intervals. Following 6 months of plaque accumulation during disease reinduction, there were significant changes (p less than 0.05) in the pocket depths, bleeding scores and attachment levels in both the SU and NS areas. These changes were accompanied by significant increases (p less than 0.05) in the proportions of spirochetes and motile rods and decreases in the proportions of coccoid cells in both the SU and NS areas. There were, however, no significant differences between the SU and NS areas when clinical and microbiologic parameters were compared. At the end of disease reinduction phase, the length of inflammatory cell infiltrate and % inflamed connective tissue had increased significantly in both the SU and NS areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Desmethylnafoxidine aziridine: an electrophilic affinity label for the estrogen receptor with high efficiency and selectivity.

Desmethylnafoxidine aziridine (Naf-Az), an affinity label for the estrogen receptor based structurally on the antiestrogen nafoxidine, has been prepared in unlabeled and in high specific activity, tritium-labeled form and has been evaluated for its apparent competitive binding, and time-dependent irreversible, covalent attachment to the estrogen receptor. Naf-Az was synthesized through a key 1,2-diaryl-3,4-dihydronaphthalene intermediate that was prepared from 6-methoxy-1-tetralone by two routes involving alternate strategies for arylation. Conversion of the diaryldihydronaphthalene to Naf-Az through a series of deprotection-activation reactions culminated in ethyleneimine displacement of a methanesulfonate. The tritium-labeled material was prepared by tritium-iodine exchange on an iodinated methanesulfonate precursor, followed by ethyleneimine displacement. Compared to our previously-prepared reagent tamoxifen aziridine (Tam-Az), Naf-Az has a higher apparent competitive binding affinity, and it reacts with the estrogen receptor in cytosol preparations and in intact MCF-7 breast cancer cells rapidly and with at least comparable efficiency and selectivity. SDS-polyacrylamide gel electrophoretic analysis confirms its selective labeling of the Mr 66,000 estrogen receptor. Naf-Az should prove to be useful in studies aimed at characterizing the properties and structure of estrogen receptors.

Affinity Labels↗
PubMed1987

AIDS and apheresis procedures--therapeutic and safety considerations.

The role of therapeutic apheresis was assessed in a number of clinical syndromes associated with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Four groups of patients were studied: AIDS with opportunistic infections, AIDS with Kaposi's sarcoma, AIDS/ARC patients with peripheral neuropathy and a patient with AIDS-related immune thrombocytopenia. Intensive plasmapheresis was shown to have no significant effects on the disease course of patients with full-blown AIDS. However, intensive plasma exchange restored normal neurologic function in the majority of patients with AIDS/ARC-related peripheral neuropathy. Selective immunoadsorption by means of protein A columns led to a sustained normalization of platelet counts in a patient with severe immune thrombocytopenia. A phase I study of AIDS-related Kaposi's sarcoma demonstrated that protein A immunoadsorption was tolerated well and was accompanied by partial responses. Patients being plasmapheresed for conditions other than AIDS were not found to be at any greater risk for acquiring AIDS-related viruses. Finally, health care professionals performing apheresis procedures on AIDS patients were not shown to be at increased risk of contracting AIDS-related viruses provided reasonable blood precautions were exercised.

AIDS-Related Complex↗
PubMed1986

Nitrosourea and nitrosocarbamate derivatives of the antiestrogen tamoxifen as potential estrogen receptor-mediated cytotoxic agents in human breast cancer cells.

We have prepared two analogs of the antiestrogen tamoxifen that incorporate known DNA-crosslinking functions, a chloroethyl nitrosourea and a nitrosocarbamate moiety, and we have tested their bioactivities in cultures of human breast cancer cells. Both compounds bind to the estrogen receptor from MCF-7 cells, with relative binding affinities of 0.18% for the nitrosocarbamate derivative and 0.35% for the nitrosourea derivative, while the affinity of tamoxifen is 1.8%, and that of estradiol is set at 100%. The tamoxifen-nitrosocarbamate compound demonstrated a dose-related cytotoxicity by the colony formation and cell proliferation assays that was not blocked by estradiol in either estrogen receptor-positive MCF-7 cells or estrogen receptor-negative MDA-MB-231 cells, and thus, was not studied further. Tamoxifen-nitrosourea (TAM-NU) showed dose-related cytotoxicity in MCF-7 cells that was blocked by estradiol, whereas its activity in MDA-MB-231 cells was unaffected by estradiol. N-2-(4-t-butylphenoxy)ethyl-N'-chloroethyl-N'-nitrosourea (BPE-NU), a control compound which contains the nitrosourea moiety but does not bind to the estrogen receptor, had no effect on cell proliferation or colony formation in MCF-7 cells, but was very inhibitory in the receptor-negative MDA-MB-231 cells. In contrast, TAM-NU was more active in the receptor-positive MCF-7 cells than in the MDA-MB-231 line. Thus, because TAM-NU appears to be active selectively against the receptor-positive cell line, and because this activity is suppressible by estradiol, its cytotoxic effect seems to be mediated via the estrogen receptor. However, since TAM-NU is active only in prolonged treatment protocols, it appears likely that its cytotoxic activity results from the hormone antagonistic effect of the hydrolysis product of TAM-NU (bis-desmethyltamoxifen), rather than from a direct receptor-mediated, DNA-directed cytotoxic action of TAM-NU itself. This study stresses the need for the use of appropriate control compounds and cell systems in order to assess whether the toxic activity displayed by hormone-cytotoxic conjugates is mediated by receptor interactions and whether it operates through the intended toxic mechanism.

Breast Neoplasms↗
PubMed1986

Beta-adrenergic responses in drug-free subjects with asthma.

Young atopic subjects with asthma who had taken no medication for 30 days and had normal pulmonary function were compared to atopic and nonatopic control subjects in several measures of beta-adrenergic response. Subjects with asthma required a larger dose of infused isoproterenol (14.3 +/- 3.9 ng/kg/min) to increase pulse pressure by a target greater than 22 mm Hg than nonatopic control subjects (8.7 +/- 3.3 ng/kg/min). Asymptomatic atopic control subjects had intermediate sensitivity (12.0 +/- 6.0 ng/kg/min) (F = 3.67; p less than 0.05). At the dose of infused isoproterenol producing the target pulse pressure response, the increase in low-frequency (1 to 8 cycles per minute) heart rate variability was less in subjects with asthma (107 +/- 34% increase in normal subjects versus 9 +/- 21% increase in subjects with asthma; p less than 0.05). In addition, subjects with the least beta-adrenergic responsiveness had the most reactive airways. Airway reactivity (assessed by the provocative concentration of methacholine causing a 20% fall in FEV1) correlated with both the dose of isoproterenol required for the target pulse pressure response (Rs = -0.46; p less than 0.05) and the isoproterenol-induced increase in low-frequency heart-rate variability (Rs = 0.47; p less than 0.05). In contrast, in lymphocytes and granulocytes from these same subjects, the cAMP response to isoproterenol and beta-adrenergic receptor number were identical in normal subjects and subjects with asthma and unrelated to airway reactivity or to cardiovascular beta-adrenergic responses. Thus, different results for beta-adrenergic responsiveness in subjects with asthma are obtained in different tests in the same subjects.

Adult↗
PubMed1986

Abnormalities of fine motor control in schizophrenia.

Response time and fine motor control during a classification task were examined in schizophrenics and nonschizophrenics. The task involved decisions about either the sensory characteristics of auditory and visual stimuli or the referential meanings of spoken words and viewed pictures. Nonschizophrenics responded more quickly and exhibited a smoother and faster motor response on all tasks. Response time and motor control were influenced by stimulus modality and the complexity of the classification task in both groups. In the analysis of motor control, the schizophrenics differed from the nonschizophrenics in exhibiting a pattern suggestive of a specific difficulty with decisions involving referential meaning. The observed motor control dysfunction in schizophrenics is a psychomotor deficit similar to previously reported abnormalities in smooth pursuit eye movement. Further, the interaction of group and task variables in the motor response suggests that decisions about the abstract referential meaning of words and pictures produce greater cognitive loads in schizophrenics than in nonschizophrenics.

Adult↗
PubMed1986

In vivo differentiation of progenitor cells of the periodontal ligament. An experimental study using physical barriers.

The present study was designed to test the hypothesis that during regeneration of cementum, the progenitor cells from periodontal ligament must come in contact with root dentin in order to differentiate into cementoblasts. After reflecting mucoperiosteal flaps, fenestration wounds were made in the buccal cortical plates of mandibular canines in 6 beagle dogs. The exposed root surfaces were curretted to remove all cementum. The exposed root surface on one side was demineralized with citric acid while the contralateral wound had saline treatment. The exposed root surfaces were then dried and pieces of Nuclepore membrane (pore size 0.1 mu) were attached to part of the exposed root surface to prevent contact of progenitor cells with root dentin. The fenestration wounds were then covered with Millipore filter to facilitate the population of wounds by progenitor cells from the periodontal ligament. Histologic analysis was performed after 3 months of healing. In specimens where the Nuclepore membrane had remained attached to root dentin, no new cementum was seen over the membrane. At the borders of the wounds and in specimens where the Nuclepore membrane had detached from root dentin, new connective tissue attachment was consistently seen. Also, root resorption was very rarely observed in both the acid-treated and control specimens. The present findings suggest that contact with root dentin may be necessary for progenitor cell differentiation into formative cells like cementoblasts.

Animals↗
PubMed1986

Nitrous oxide: clinical and electrophysiologic investigation of neurologic complications.

Prolonged exposure to nitrous oxide produces a recognized neurologic syndrome. We report clinical and electrophysiologic studies of nervous system involvement in a 25-year-old student who abused nitrous oxide. He developed signs of a sensorimotor polyneuropathy and of myelopathy. Routine blood studies, CSF examination, and myelogram were normal. Clinical electrophysiologic studies were performed serially. Nerve conduction studies demonstrated reduced amplitude and slowed sensory potentials, and mildly prolonged late responses. Sensory evoked potentials revealed prolonged latency of scalp-evoked potentials from tibial nerve stimulation with normal median nerve values. The foveal visual evoked potential was delayed in the right eye, with normal visual acuity, funduscopic examination, and spatial contrast sensitivity. Repeat electrophysiologic studies demonstrated improvement. Nitrous oxide produces multifocal reversible dysfunction within the nervous system similar to that described in patients with vitamin B12 deficiency.

Adult↗
PubMed1986

Improvement in organically disturbed behavior with trazodone treatment.

Four elderly patients with severe organic brain syndromes and disturbed behavior were treated with trazodone after therapy with neuroleptics had been ineffective. The behavior of all four patients improved substantially. In each case, the clinical presentation did not suggest a depressive illness, and many of the disturbed behaviors, such as hypersexuality, are not generally considered characteristic of depression. The improvement in behavior may be related to the taming effect of trazodone in animal models of aggression. This effect is not shared by other antidepressants; thus, trazodone may have unique value as an alternative to neuroleptics for the treatment of organically disturbed behavior.

Aged↗
PubMed1986

Reliability of Andreasen's thought, language and communications disorder scale.

The study of disordered thinking has been hampered by a lack of clinical instruments aimed at the measurement of thought disorder. Andreasen has proposed a rating scale for thought disorder (TLC) and reported on its reliability and preliminary aspects of its validity. In our study, a psychiatrist and physician assistant rated 98 psychiatric inpatients using the TLC and BPRS. Interrater reliability ranged from 0.35 to 0.80 (weighted kappa) on 18 aspects of thought disorder and one global item. The order of reliability for the 18 individual items was strongly correlated between the Andreasen sample and our own (r = 0.77). While the BPRS thought disorder scale was significantly related to the global rating of thought disorder on the TLC (r = 0.71), only half of the variance in thought disorder measured by the TLC was accounted for by the BPRS factor. Thus, this study supports Andreasen's contention that the TLC is a reliable instrument and suggests that the instrument may provide additional information about thinking disorders.

Communication↗
PubMed1985

Measuring thought disorder with clinical rating scales in schizophrenic and nonschizophrenic patients.

The distinction between disorders of thought structure and disorders of thought content in a diagnostically heterogeneous psychiatric population was empirically tested using factor analysis applied to the item scores on two common clinical rating scales, the Brief Psychiatric Rating Scale and Andreasen's Thought, Language, and Communication Scale. The factor structure supported the separation of disordered thinking into disorders of thought content and disorders of thought structure or communication. Additionally, our results indicate that both aspects of disordered thinking are present in schizophrenic and manic patients; neither is specifically characteristic of schizophrenia. Indeed, disordered thought structure appears to be more common or worse in the manic patient than in the schizophrenic patient.

Bipolar Disorder↗
PubMed1985

Low molecular weight measles immunoglobulin M in subacute sclerosing panencephalitis and acute measles.

Thirty eight patients with subacute sclerosing panencephalitis (SSPE) were investigated. Five patients who previously had measles immunoglobulin M (IgM) detected in unfractionated serum and cerebrospinal fluid (CSF) had measles IgM exclusively in the low molecular weight (LMW) fractions of serum and CSF. Measles IgM had previously not been found in unfractionated serum from 33 patients but was detected exclusively in the LMW fractions of serum from 30 patients. Seven children with acute measles had the expected high molecular weight (HMW) measles IgM in serum but 5 also had LMW measles IgM. Four young adults who had had measles in childhood had neither HMW nor LMW measles IgM in their sera.

Acute Disease↗
PubMed1985

An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens: studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor.

Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10(-11)-10(-6) M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day X 50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.

Binding, Competitive↗
PubMed1985

An evaluation of tricalcium phosphate implants in human periodontal osseous defects of two patients.

This study evaluated the use of tricalcium phosphate (TCP) ceramic implant material in periodontal osseous defects. Thirteen defects in two patients were treated with mucoperiosteal flaps and placement of TCP. The defects were evaluated clinically and radiographically utilizing standardized probe placement and radiographic technique. Clinically, there was a mean probing pocket reduction of 4.5 mm as a result of a mean gain of clinical probing attachment level of 2.0 mm and a mean gingival recession of 2.5 mm. Radiographically, there was a mean "fill" of 1.8 mm. Six teeth were removed by block biopsy for histologic analysis, three at 3 months, one at 6 months and two a 9 months. The TCP particles were well tolerated and encapsulated by fibrous connective tissue, but the particles did not stimulate new bone growth. The junctional epithelium ended 1.62 mm coronal to the apical extent of a reference notch placed at the base of the defect. Although new cementum was observed, there was limited evidence of new attachment.

Adult↗