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Biomedical subjects

D M Simpson

Publications and source records attributed to D M Simpson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Pediatric emergency room visits: a risk factor for acquiring measles.

In recent years, measles outbreaks have occurred among unimmunized children in inner cities in the United States. From May 1988 through June 1989, 1214 measles cases were reported in Los Angeles, and from October 1988 through June 1989, 1730 cases were reported in Houston. More than half of cases were in children younger than 5 years of age, most of whom were unvaccinated. Of cases of measles in preschool-aged children, nearly one fourth in Los Angeles and more than one third in Houston were reported by one inner-city emergency room. To evaluate whether emergency room visits were a risk factor for acquiring measles, in Los Angeles, 35 measles patients and 109 control patients with illnesses other than measles, and in Houston, 49 measles patients and 128 control patients, who visited these emergency rooms, were enrolled in case-control studies. Control patients were matched to case patients for ethnicity, age, and week of visit. Records were reviewed to determine whether case patients had visited the emergency room during the period of potential measles exposure, which was defined as 10 to 18 days before rash onset, and whether control patients had visited 10 to 18 days before their enrollment visit. In Los Angeles, 23% of case patients and 5% of control patients (odds ratio = 5.2, 95% confidence interval = 1.7, 15.9; P less than .01), and in Houston, 41% of case patients and 6% of control patients (odds ratio = 8.4, 95% confidence interval = 3.3, 21.2; P less than .01), visited the emergency room during these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Human immunodeficiency virus wasting syndrome may represent a treatable myopathy.

We evaluated 5 patients with the diagnosis of HIV wasting syndrome. None had severe diarrhea or other causes for malabsorption. All had myopathy by clinical, laboratory, and muscle biopsy criteria. Withdrawal of azidothymidine in 3 patients did not lead to improvement. Corticosteroid therapy was effective in 3 patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Clinical Q fever in Northern Ireland 1962-1989.

Q fever was diagnosed in 443 patients in Northern Ireland between 1962 and 1989. From 1986 onwards there was an increase, which peaked in 1989 with 107 cases of whom 47 were infected in Ballycastle, Co Antrim. There were three outbreaks and 21 clusters of patients with Q fever. Most cases were in April and May which correlated with the peak lambing and calving season. Q fever mainly affected males in the 40-49 year old age group. County Antrim had the highest prevalence rate of 40/100,000 population and also had the most sheep. The number of sheep in Northern Ireland has doubled in the past ten years. Q fever was strongly associated with occupation and animal contact. Eighty-seven patients (19.6%) drank unpasteurized milk. The commonest presenting illnesses were pneumonia (62.8%), influenza-like illness (24.6%), involvement of the heart (9.0%) and hepatitis (1.6%). Thirty-two patients (7.2%) had endocarditis, 20 of whom had prosthetic valves and three of whom died. Coxiella burnetii was present on valves removed from seven patients.

Adolescent↗
PubMed1989

Voluntary movement dysfunction in schizophrenics.

Several aspects of fine motor control were compared in schizophrenics and two control populations. The motor behavior analyzed was a button-press response in a forced choice paradigm. Three areas of abnormality were seen in schizophrenics: first, the interval preceding the motor response was characterized by reduced motor steadiness prior to the button-press response; second, the motor response was made with excessive force (hyperdynamia); and third, the agonist-antagonist synchrony (motor reversal) was impaired. Schizophrenics on and off neuroleptics did not differ on any measure of motor control, but schizophrenics with clinically observed tardive dyskinesia were found to have significantly less steadiness prior to the motor response than other schizophrenics.

Adult↗
PubMed1988

Human immunodeficiency virus-associated myopathy: analysis of 11 patients.

Neuromuscular disorders reported in association with human immunodeficiency virus (HIV) infection include several forms of peripheral neuropathy and polymyositis. We report 11 patients with HIV-associated myopathy. Five patients with acquired immunodeficiency syndrome (AIDS), 2 with AIDS-related complex, and 4 otherwise asymptomatic HIV-infected patients developed progressive proximal muscle weakness. Serum creatine phosphokinase levels were elevated and electromyography revealed abnormal spontaneous activity and myopathy in most patients. All 8 muscle biopsy specimens showed fiber necrosis. Four had inflammatory infiltrates, and nemaline rod bodies were prominent in 3. Immunosuppressant therapy in 5 patients resulted in improvement. Attempts at viral localization in 4 muscle biopsy specimens were unsuccessful. These findings suggest a distinct association between HIV infection and myopathy with features atypical for polymyositis.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Low and high molecular weight cytomegalovirus-specific immunoglobulin M antibody in renal transplant patients with cytomegalovirus infections.

Sera from 27 renal transplant patients with primary and recurrent CMV infections and which were known to contain CMV-specific IgM antibodies were investigated by indirect immunofluorescence for the presence of virus-specific high molecular weight IgM (19S IgM) and low molecular weight IgM (7S IgM). After sucrose gradient fractionation of the sera, 19S IgM was found in all 27 patients, whereas 7S IgM was present in 11 out of 19 (56%) patients with primary CMV infection and in 1 out of 8 (12%) patients with recurrent CMV infection. The presence of 7S IgM was unrelated to the titre of the virus-specific IgM in whole serum. The presence of IgM rheumatoid factor was monitored by a sensitive fluorescence assay using measles virus antigen/antibody complexes. The absorption of the serum fractions with heat-aggregated gamma globulin failed to remove the specific IgM staining indicating that it was not due to IgM rheumatoid factor. On the other hand adsorption with protein A/sepharose removed the specific IgM staining from the 7S IgM fractions but not from the 19S IgM fractions. This suggests that specific 19S and 7S IgM antibodies may belong to different subclasses of IgM.

Antibodies, Viral↗
PubMed1988

Spectral analysis of heart rate indicates reduced baroreceptor-related heart rate variability in elderly persons.

Spectral analysis of the cardiac interbeat interval was used to examine baroreceptor-related supine and standing heart rate variability (HRV) in young (less than 40 years of age) and elderly (greater than 60 years of age) healthy volunteers. Heart rates and blood pressures were examined also. When supine, average heart rate, systolic and diastolic blood pressure, and HRV for the young volunteers were 66.5 bpm, 113.0/64.3 mmHg, and 5.74 log units of relative power, respectively. The same values for the elderly group were 65.4 bpm, 126.3/74.0 mmHg, and 4.43 log units. Statistical analysis revealed that, compared to the young volunteers, supine elderly volunteers had similar heart rates, higher blood pressures, and lower baroreceptor HRV. There was little change in blood pressure in either group upon standing. However, upon standing, heart rate increased 17.7 bpm and baroreceptor HRV increased to 6.58 (+ 14.6%) in the younger volunteers. This was significantly different from the elderly volunteers, whose heart rate increased by only 10.9 bpm and their HRV to 4.72 (+ 6.5%). These results indicate that much of the reduction in HRV in old age results from decreases in baroreceptor modulation of heart rate. In addition, the difference between young and old persons is greatest in the standing position because elderly individuals exhibit less recruitment of baroreceptor activity with postural change.

Adult↗
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↗