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Biomedical subjects

M P Rogers

Publications and source records attributed to M P Rogers.

At least 19 recordsLinked to original sources

DSM-IV and the disappearance of agoraphobia without a history of panic disorder: new data on a controversial diagnosis.

OBJECTIVE: This analysis describes subjects who met rigorous criteria for DSM-III-R agoraphobia without a history of panic disorder and makes inferences from these data regarding relationships among agoraphobia without a history of panic disorder, panic disorder, and panic disorder with agoraphobia. METHOD: Twenty-six subjects (seven men and 19 women) with agoraphobia without a history of panic disorder were identified from among 711 subjects recruited for a multicenter, longitudinal anxiety disorder study. Narrative transcripts prepared by raters from study evaluations were coded for limited symptom attacks, situational panic, catastrophic cognitions, and possible precipitants and stressors, course, and somatic and psychosocial treatments received. RESULTS: Sixty-five percent of the subjects reported experiences consistent with situational panic attacks, and 57% had definite or probable limited symptom attacks; these attacks usually preceded or appeared at the same time as avoidance behavior. Eighty-one percent had catastrophic cognitions associated with agoraphobia. Twenty-six percent reported a likely precipitating factor for symptom onset, and 30% reported a definite or probable major life stressor within 6 months before symptom onset. Cognitive-behavioral treatments were relatively infrequently used. Course was relatively unchanged across the follow-up period. CONCLUSIONS: These data support a view of agoraphobia without a history of panic disorder on a continuum with uncomplicated panic disorder and with panic disorder and agoraphobia, rather than as a separate diagnosis.

Adult

High-dose oral tamoxifen, a potential multidrug-resistance-reversal agent: phase I trial in combination with vinblastine.

BACKGROUND: P-glycoprotein mediates resistance to natural-product anti-neoplastic agents like vinblastine through an active transport process resulting in reduced intracellular concentration of these agents. The triphenylethylene antiestrogen tamoxifen and its major metabolite N-desmethyltamoxifen at concentrations of 4-6 microM enhance the intracellular concentration of natural-product antineoplastics and augment the cytotoxicity of such drugs three-fold to 10-fold in a variety of human and murine cell lines. PURPOSE: On the basis of these preclinical findings, we conducted a phase I clinical trial of high-dose, oral tamoxifen administered in conjunction with a 5-day continuous infusion of vinblastine. METHODS: We studied 53 patients with advanced epithelial tumors. Tamoxifen was given orally as a loading dose on day 1, followed by two doses a day on days 2-13. Vinblastine was given as a 120-hour continuous infusion (1.5 mg/m2 per day) on days 9-13 of each tamoxifen course. The starting dose of tamoxifen was 40 mg/m2 administered twice a day following a loading dose of 150 mg/m2. The maximum dose was 260 mg/m2 twice a day following a loading dose of 680 mg/m2. Treatment cycles were repeated every 28 days. RESULTS: The dose-limiting toxic effects of tamoxifen were neurologic and began within 3-5 days after the start of treatment. They consisted of tremor, hyperreflexia, dysmetria, unsteady gait, and dizziness. One patient experienced a grand mal seizure 24 hours after the last tamoxifen dose. Toxic effects were rapidly reversible. Asymptomatic prolongation of the QT interval on electrocardiogram occurred at doses of tamoxifen of 80 mg/m2 or higher given twice a day. No coagulation or ophthalmologic abnormalities occurred. Tamoxifen did not enhance the toxicity of vinblastine. Mean plasma concentrations of tamoxifen or N-desmethyltamoxifen at 260 mg/m2 tamoxifen given twice a day for 13 days were 6.04 and 6.56 microM, respectively. There was no relationship between plasma antiestrogen content and the development of neurotoxic effects. CONCLUSIONS: Tamoxifen at 150 mg/m2 given twice a day following a loading dose of 400 mg/m2 results in plasma levels of tamoxifen and N-desmethyltamoxifen of 4 and 6 microM, respectively, without dose-limiting toxicity. We recommend this dose for phase II trials of tamoxifen to modulate P-glycoprotein-mediated drug resistance. IMPLICATIONS: Our study demonstrates that high-dose tamoxifen can be safely administered and that plasma concentrations that may inhibit P-glycoprotein function can be achieved.

ATP Binding Cassette Transporter, Subfamily B, Mem

Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial.

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance may be mediated by repair of chloroethylated guanine before stable cross-linking occurs. Guanine adducts may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (O6-AGAT). Such repair irreversibly inactivates O6-AGAT. Streptozotocin (STZ) forms adducts at the O6 position of guanine; repair of these adducts consumes O6-AGAT. In vivo STZ potentiates BCNU cytotoxicity. The purpose of this trial was to determine the maximum tolerated dose of BCNU that can be administered together with STZ. The STZ dose was 500 mg/m2/day for 4 days and was not escalated. BCNU was given 4 h after the third dose of STZ at a starting dose of 75 mg/m2. A total of 43 patients were entered in the study. There were 4 dose escalations, reaching a maximum tolerated BCNU dose of 175 mg/m2. At this dose, thrombocytopenia was the dose-limiting toxicity (one patient, 25-49 x 10(9)/liter; 2 patients, less than 25 x 10(9)/liter); neutropenia was less severe (2 patients, 2.0-3.9 x 10(9)/liter, 1 patient, 1.0-1.9 x 10(9)/liter). Two other commonly seen toxicities were elevations in the serum alkaline phosphatase and mild elevations in the serum creatinine. Peripheral blood lymphocyte O6-AGAT levels decreased from a mean of 212 fmol/mg protein pretherapy to 8.2 fmol/mg protein on day 3 prior to BCNU (P = 0.03). Three partial responses were seen. There were no therapy-related fatalities, and toxicity was easily managed. This study established that 150 mg of BCNU can be administered safely together with STZ, 500 mg/m2/day for 4 days. Additional studies are required to determine whether O6-AGAT-mediated BCNU resistance is suppressed.

Adult

Psychosocial adjustment in juvenile arthritis.

Psychosocial adjustment in 102 children with arthritis, ages 4-16, and their families was assessed by parents, who completed the Child Behavior Checklist (CBCL) and Profile of Mood States (POMS). On average, parental distress (POMS) was lower than reference norms. POMS distress was correlated with children's behavioral problems (r = .41) but not with children's social competence (r = .15). General linear models explained 25% of the variance in CBCL behavioral problem scores. Older age was associated with more behavior problems in males, but not females. Disease severity and disease activity were also associated with behavioral problems. Although 27% of the variance in CBCL social competence could be explained, no single predictor variable was especially strong. Poorer social competence was associated with older age and shorter disease duration. Teenagers, especially those with recent onset and those with mild disease activity, may be at increased risk for psychosocial maladjustment.

Adaptation, Psychological

I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study.

Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bi-temporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role.

Adolescent

Phosphorylation and activation of hormone-sensitive lipase in isolated macrophages.

Hormone-sensitive lipase (HSL) is responsible for the neutral cholesterol ester hydrolase activity in macrophages. Incubation of intact WEHI macrophages or mouse peritoneal macrophages leads to phosphorylation of HSL, which is increased by incubation with either dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine or okadaic acid. Correspondingly, these agents also activate neutral cholesterol ester hydrolase activity in intact WEHI cells. Regulation of mobilisation of esterified cholesterol in macrophages may be of antiatherogenic value, which this model system now allows us to investigate further.

1-Methyl-3-isobutylxanthine

Regulation of lipoprotein lipase activity and mRNA content in rat epididymal adipose tissue in vitro by recombinant tumour necrosis factor.

Tumour necrosis factor (TNF) has previously been shown to decrease lipoprotein lipase (LPL) activity and mRNA levels in 3T3-L1 cells and in adipose tissue from rats and guinea pigs when injected in vivo, but not to alter LPL activity in human adipocytes incubated in vitro. The effect of recombinant human TNF on LPL activity and mRNA levels in rat epididymal adipose tissue incubated in vitro was examined. LPL activity and mRNA levels fell in adipose tissue taken from fed rats and incubated in Krebs-Henseleit bicarbonate medium with glucose. The addition of insulin and dexamethasone prevented these falls. TNF (400 ng/ml) produced a fall of approx. 50% in LPL activity after 2 h of incubation and of approx. 30% in LPL mRNA levels after 3 h. TNF did not decrease LPL activity in isolated adipocytes. These results demonstrate that rat adipose tissue incubated in vitro is responsive to TNF whereas isolated adipocytes are not.

Adipose Tissue

Sensitivity of freshly isolated ovine adipocytes to inhibition of lipolysis by insulin.

1. Ovine adipocytes were isolated in the presence of adenosine to minimize cell damage and were incubated at a low cell concentration. 2. Insulin sensitivity of lipid metabolism was retained. 3. Insulin inhibited basal lipolysis by 61% and isoproterenol- and adenosine deaminase-stimulated lipolysis by 84%. 4. Insulin increased glucose conversion to cell lipid by 3-fold.

Adipose Tissue

Delirium after elective orthopedic surgery: risk factors and natural history.

Forty-six orthopedic patients were studied to determine the incidence, natural history, and risk factors associated with post-operative delirium. Pre-operatively, patients were given a neuropsychological screening evaluation, the Mood Adjective Checklist (MACL), the Zung Depression Scale, the Anxiety Inventory Scale, and the Health Assessment Questionnaire (HAQ). A psychiatrist interviewed each patient on post-op day four for evidence of delirium as defined by DSM III criteria. Of the patients studied, thirteen (26%) were possibly or definitely delirious following surgery. Treatment with propranolol, scopolamine, or flurazepam (Dalmane) conferred a relative risk for delirium of 11.7 (p = 0.0028). Delirium was associated with increased post-operative complications (p = 0.01), poorer post-operative mood (p = 0.06), and an increase of about 1.5 days in length of stay (not significant). Delirious patients were significantly less likely than matched controls to improve in function at six months compared with a pre-operative baseline HAQ (t = 6.43, p less than 0.001).

Aged

Psychologic aspects of pregnancy in patients with rheumatic diseases.

Under normal conditions, pregnancy constitutes a developmental crisis. In high-risk pregnancies, the stages of adaptation and attachment to the developing fetus may be delayed. Prior miscarriage or loss of a more fully developed baby, which is common in SLE, may further challenge the bonding process. In deciding whether or not to have a baby, couples need current medical information provided by an internist/rheumatologist, in close coordination with the obstetrician.

Adaptation, Psychological

Detection of acute gastrointestinal bleeding by intra-arterial Tc-99m sulfur colloid scintigraphy in a canine model. Preliminary study.

The diagnostic sensitivities of arteriography, intravenous (IV) Tc-99m sulfur colloid scintigraphy, and intra-arterial (IA) Tc-99m sulfur colloid scintigraphy were evaluated in a canine model of gastrointestinal bleeding. Fifteen dogs were studied at bleeding rates ranging from .4 to 1.0 ml/minute. All three studies were obtained in six of the 15 dogs. Intravenous scintigraphy was superior to angiography in two cases, inferior in three, and equal in one. No significant difference could be shown between these two tests at these bleeding rates. Intra-arterial scintigraphy was superior to angiography in four cases and equal in two (P = .06). It was superior to IV scintigraphy in five cases and inferior in one (P = .10). In this small preliminary study, IA scintigraphy appears to be superior to the other two modalities and may prove useful in the detection of acute bleeding at the time of negative arteriography, and in serial studies in patients receiving Pitressin.

Acute Disease

Computerized display of past test results. Effect on outpatient testing.

STUDY OBJECTIVE: To determine the effect of displaying previous results of diagnostic tests on the ordering of selected outpatient tests. DESIGN: Sixteen-week controlled trial with a 13-week pre-intervention and 8-week post-intervention observation periods. Patients were randomly assigned to intervention or control groups so that each physician was his or her own control. Only scheduled visits were included. Randomization occurred before the pre-intervention observation period. SETTING: Academic primary care general medicine clinic affiliated with an urban general hospital. SUBJECTS: Pre-intervention period: 111 physicians (97 internal medicine residents, 14 faculty internists), 4683 patients, 5942 scheduled visits. INTERVENTION period: same 111 physicians, 5946 patients, 8148 visits. Post-intervention period: 76 physicians (62 residents, 14 faculty), 2571 patients, 2858 scheduled visits. INTERVENTION: With an order for one of eight selected diagnostic tests through microcomputer workstations, a window was opened on the screen and previous test results were displayed along with the time interval between the first and last result. Tests were ordered for control patients into the same workstations without previous results displayed. MEASUREMENTS AND MAIN RESULTS: Previous results of one or more study tests were available for display for 96% of scheduled patients. Significantly lower results (p less than 0.05 by paired t-test) for the selected tests were found for intervention patient visits than for control visits: charges per visit (mean +/- SE) for intervention patients $12.17 +/- 0.62, compared with $13.99 +/- 0.77 for controls, a 13.0% difference; tests per visit were 0.51 +/- 0.03, compared with 0.56 +/- 0.03, an 8.5% difference. The number of study tests ordered decreased significantly for intervention patients (16.8%) and for controls (10.9%). During the post-intervention period, ordering of study tests increased for both groups, but the increase from the intervention period was not significant. CONCLUSIONS: Presenting physicians with previous test results reduced the ordering of those tests. The actual effect may have been greater than 13%, because there were reductions in study tests ordered for both intervention and control patients during the intervention period when compared with the pre-intervention period, and both tended to rise after the intervention, or display, was turned off.

Data Display

Inhibition of human and rat lipoprotein lipase by high-density lipoprotein.

The hydrolysis in vitro of preactivated Intralipid (an artificial triacylglycerol-phospholipid emulsion) by rat adipose tissue lipoprotein lipase is inhibited by rat high-density lipoprotein (HDL). The aim of this work was to investigate whether human lipoprotein lipase was also inhibited, the mechanism of inhibition of the rat enzyme by HDL, and the role of the various individual apolipoproteins. Both human and rat lipoprotein lipase from post-heparin plasma are inhibited by HDL. This inhibition is considerably decreased if the HDL is first made 'apolipoprotein poor' by removal of some transferable apolipoproteins. In contrast, both native and apolipoprotein poor HDL inhibit the hydrolysis of Intralipid by rat hepatic lipase. Apolipoproteins C and E, either free in solution or attached to lipid vesicles, inhibit the hydrolysis of activated Intralipid by rat lipoprotein lipase to a maximum of 85% and 50%, respectively. Apolipoprotein A attached to vesicles gives little inhibition. HDL apolipoprotein and apolipoprotein C compete with the substrate for binding to lipoprotein lipase with apolipoprotein C having a higher affinity for the enzyme than HDL apolipoprotein. The inhibition of lipoprotein lipase by HDL can be explained by the association of the constituent apolipoproteins, in particular apolipoprotein C, with the enzyme so that there is less enzyme available to act on substrate.

Animals