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Biomedical subjects

D A Davis

Publications and source records attributed to D A Davis.

At least 19 recordsLinked to original sources

Detection of serum antibodies to a Kaposi's sarcoma-associated herpesvirus-specific peptide.

Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) may play an etiologic role in the pathogenesis of KS. In an attempt to assess KSHV/HHV-8 infection, an ELISA was developed using an 18-amino acid peptide from a putative minor capsid protein of KSHV/HHV-8 conjugated to bovine serum albumin. Overall, sera from human immunodeficiency virus type 1 (HIV-1)-positive patients with KS had a higher reactivity in the assay than did sera from HIV-1-positive patients without KS (P = .018). Of 35 HIV-1-positive patients with KS, 60% were antibody positive, compared with 27% of 33 HIV-1-positive patients without KS. Of 30 healthy blood donors, 20% were antibody positive. The ELISA responses did not correlate with antibody titers to Epstein-Barr virus. Given the homology and antigenic relatedness between KSHV/HHV-8 and Epstein-Barr virus, serologic assays involving unique KSHV/HHV-8 peptides may prove to be valuable in defining the epidemiology and clinical expression of this virus.

Acquired Immunodeficiency Syndrome

Leptospira interrogans serovar grippotyphosa infection in dogs.

Leptospirosis attributed to infection with serovar grippotyphosa was diagnosed in 11 dogs. In naturally and experimentally infected dogs, a stereotypic serologic response to infection with Leptospira serovar grippotyphosa was detected. Although the highest serum antibody titers developed against serovar grippotyphosa, most dogs also had lower titers against serovars bratislava and pomona. Acute renal failure was evident in 10 dogs. One dog died prior to initiation of treatment; the remaining 10 dogs were treated with antibiotics and fluids. Two dogs were euthanatized, 2 dogs recovered without clinical or biochemical evidence of residual renal dysfunction, and 6 dogs recovered but had varying degrees of renal insufficiency. Hepatic involvement appeared to be a minor component of the disease in these dogs. Our results indicate that Leptospira serovar grippotyphosa infection is an important problem in dogs and should be considered when evaluating a dog with renal failure.

Acute Kidney Injury

Effects of amphetamine and 6-hydroxydopamine lesions on reserpine-induced oral dyskinesia.

The present study examined whether reserpine-induced oral dyskinesia is mediated by release of residual endogenous dopamine. Amphetamine produced a dose-dependent change in reserpine-induced oral dyskinesia in which the response was exacerbated by 0.6 mg/kg amphetamine and inhibited by 1 mg/kg. The latter dose also produced stereotypy that may have interfered with expression of reserpine-induced oral dyskinesia. Nigrostriatal 6-hydroxydopamine lesions attenuated expression of reserpine-induced oral dyskinesia. These lesions did not reduce locomotor activity, however, indicating that the attenuation of reserpine-induced oral dyskinesia was not due to a general depressant effect of the lesions on motor behavior. These results suggest that increasing dopamine release by administration of amphetamine exacerbates reserpine-induced oral dyskinesia, whereas decreasing the amount of releasable dopamine in the striatum by 6-hydroxydopamine lesions attenuates reserpine-induced oral dyskinsia. These findings may have implications for understanding tardive dyskinesia and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia.

Adrenergic Agents

Regulation of HIV-1 protease activity through cysteine modification.

The homodimeric protease of the human immunodeficiency virus 1 contains two cysteine residues per monomer which are highly conserved among viral isolates. However, these cysteine residues are not essential for catalytic activity which raises the question of why they are conserved. We have found previously that these cysteine residues are unusually susceptible to oxidation by metal ions, and this results in inhibition of protease activity. Recombinant protease mutants (C67A, C95A, and the double mutant C67A,C95A) were prepared to assess the possible role of these cysteines in redox regulation of the enzyme. Mixed disulfides were formed between the cysteine residues of the enzymes and low molecular weight thiols. Enzyme activity was lost when a mixed disulfide was formed between 5,5'-dithiobis(2-nitrobenzoic acid) and cysteine 95, while the same mixed disulfide at cysteine 67 reduced activity by 50%. This effect was reversible as normal activity could be restored when the enzyme was treated with dithiothreitol. The cysteines could also be modified with the common cellular thiol glutathione. Modification with glutathione was verified by mass spectrometry of the protein peaks obtained from HPLC separation. Glutathiolation of cysteine 95 abolished activity whereas modification at cysteine 67 increased the k(cat) by more than 2-fold with no effect on K(m). In addition, glutathiolation at cysteine 67 markedly stabilized the enzyme activity presumably by reducing autoproteolysis. These results demonstrate one possible mechanism for regulation of the HIV-1 protease through cysteine modification and identify additional targets for affecting protease activity other than the active site.

Catalysis

Infant thoracic surgery: procedure-dependent pulmonary response.

Respiratory insufficiency is a common complication of thoracic surgery in infants. To better define this dysfunction, pulmonary compliance (CL) and resistance (R) were measured for 17 infants who underwent common thoracic procedures: Blalock-Taussing shunting (n = 7) repair of congenital coarctation of the aorta (n = 10). Measurements were obtained preoperatively and 0, 1, and 3 days postoperatively. Preoperatively, CL was lower and R was similar for the two groups. Both groups had decreased CL and increased R on postoperative day 0; infants with coarctation had recovery to preoperative values by postoperative day 1 for CL, and day 3 for R. CL and R did not return to the preoperative values by postoperative day 3 in infants with a shunt procedure. The changes in R were greater than those in CL for both groups in the postoperative period. These data indicate that such thoracic procedures are associated with pulmonary morbidity that is airway-predominant, and that the degree of compromise and the time until recovery are, in part, procedure-specific.

Airway Resistance

Lichen nitidus.

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Humans

Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: radiation port scleroderma.

BACKGROUND: An association between systemic scleroderma, radiation, and breast cancer has been recognized. However, localized scleroderma in the radiation port of breast cancer patients has been rarely described. OBJECTIVE: Our purpose was to describe the concurrence of localized scleroderma, supervoltage radiation, and breast carcinoma. METHODS: Patients were prospectively evaluated in a tertiary care cancer center, and the literature was reviewed. RESULTS: We describe six patients with breast cancer in whom localized scleroderma developed within their radiation port. CONCLUSION: Radiation port localized scleroderma can be a sequela of supervoltage radiation therapy in patients with breast cancer. Recognition is important because localized scleroderma can clinically mimic recurrent breast carcinoma.

Breast Neoplasms

No magic bullets: a systematic review of 102 trials of interventions to improve professional practice.

OBJECTIVE: To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes. DATA SOURCES: MEDLINE, SCISEARCH, CINAHL and the Research and Development Resource Base in CME were searched for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive. STUDY SELECTION: Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed random or quasi-random allocation methods in their study designs to assign individual subjects or groups. Interventions included such activities as conferences, outreach visits, the use of local opinion leaders, audit and feedback, and reminder systems. DATA EXTRACTION: Details extracted from the studies included the study design; the unit of allocation (e.g., patient, provider, practice, hospital); the characteristics of the targeted health care professionals, educational interventions and patients (when appropriate); and the main outcome measure. DATA SYNTHESIS: The inclusion criteria were met by 102 trials. Areas of behaviour change included general patient management, preventive services, prescribing practices, treatment of specific conditions such as hypertension or diabetes, and diagnostic service or hospital utilization. Dissemination-only strategies, such as conferences or the mailing of unsolicited materials, demonstrated little or no changes in health professional behaviour or health outcome when used alone. More complex interventions, such as the use of outreach visits or local opinion leaders, ranged from ineffective to highly effective but were most often moderately effective (resulting in reductions of 20% to 50% in the incidence of inappropriate performance). CONCLUSION: There are no "magic bullets" for improving the quality of health care, but there are a wide range of interventions available that, if used appropriately, could lead to important improvements in professional practice and patient outcomes.

Humans

Inhibition of the human immunodeficiency virus-1 protease and human immunodeficiency virus-1 replication by bathocuproine disulfonic acid Cu1+.

The protease encoded by the human immunodeficiency virus-1 (HIV-1) is essential for processing viral polyproteins which contain the enzymes and structural proteins required for the infectious virus. It was previously found that cupric chloride, in the presence of dithiothreitol or ascorbic acid, could inhibit the HIV-1 protease. It was suggested that a Cu1+ chelate was the moiety responsible for inhibition of the protease. This hypothesis has now been investigated directly by utilizing the stable Cu1+ chelate, bathocuproine disulfonic acid Cu1+ (BCDS-Cu1+). BCDS-Cu1+ inhibited the HIV-1 wild type protease as well as a mutant HIV-1 protease lacking cysteines. BCDS-Cu1+ was a competitive inhibitor of the mutant HIV-1 protease with an apparent Ki of 1 microM. Replication of HIV-1 in human lymphocytes and the cytotoxic effect of HIV-1 in CEM cells was inhibited by micromolar BCDS-Cu1+. Inhibition of the protease and of HIV replication by BCDS-Cu1+ was dependent on the presence of Cu1+ as BCDS alone was ineffective. EDTA blocked the inhibition of the protease by Cu1+ but was unable to block inhibition of the protease by BCDS-Cu1+, indicating that the Cu1+ complex was the inhibitory agent. The apparent IC50 for BCDS-Cu1+ on the inhibition of replication by primary isolates of HIV-1 was 5 microM. However, BCDS-Cu1+ did not affect polyprotein processing in an H9 cell line chronically infected with HIV-1, indicating that BCDS-Cu1+ acts by yet another mechanism to block HIV infection. Other possible targets for BCDS-Cu1+ include inhibition of viral adsorption and/or inhibition of the HIV-1 integrase.

Antiviral Agents

Changing physician performance. A systematic review of the effect of continuing medical education strategies.

OBJECTIVE: To review the literature relating to the effectiveness of education strategies designed to change physician performance and health care outcomes. DATA SOURCES: We searched MEDLINE, ERIC, NTIS, the Research and Development Resource Base in Continuing Medical Education, and other relevant data sources from 1975 to 1994, using continuing medical education (CME) and related terms as keywords. We manually searched journals and the bibliographies of other review articles and called on the opinions of recognized experts. STUDY SELECTION: We reviewed studies that met the following criteria: randomized controlled trials of education strategies or interventions that objectively assessed physician performance and/or health care outcomes. These intervention strategies included (alone and in combination) educational materials, formal CME activities, outreach visits such as academic detailing, opinion leaders, patient-mediated strategies, audit with feedback, and reminders. Studies were selected only if more than 50% of the subjects were either practicing physicians or medical residents. DATA EXTRACTION: We extracted the specialty of the physicians targeted by the interventions and the clinical domain and setting of the trial. We also determined the details of the educational intervention, the extent to which needs or barriers to change had been ascertained prior to the intervention, and the main outcome measure(s). DATA SYNTHESIS: We found 99 trials, containing 160 interventions, that met our criteria. Almost two thirds of the interventions (101 of 160) displayed an improvement in at least one major outcome measure: 70% demonstrated a change in physician performance, and 48% of interventions aimed at health care outcomes produced a positive change. Effective change strategies included reminders, patient-mediated interventions, outreach visits, opinion leaders, and multifaceted activities. Audit with feedback and educational materials were less effective, and formal CME conferences or activities, without enabling or practice-reinforcing strategies, had relatively little impact. CONCLUSION: Widely used CME delivery methods such as conferences have little direct impact on improving professional practice. More effective methods such as systematic practice-based interventions and outreach visits are seldom used by CME providers.

Decision Making

Effects of halothane on the immature lamb heart.

The choice of anesthesia during pregnancy and fetal operations is controversial. Halothane frequently is used, but its direct effects on fetal cardiac performance are unknown. The effects of halothane on fetal cardiac mechanics were studied in 8 fetal lamb hearts (135 days' gestation) using a modified Langendorff model connected to a membrane oxygenator. The perfusate consisted of oxygenated maternal blood at a constant flow temperature, hematocrit value, and glucose level. Coronary blood flow, left ventricular systolic pressure, left ventricular end-diastolic pressure, and the developed left ventricular pressure at a fixed volume were evaluated at baseline and after the addition of incremental concentrations of halothane to the perfusate through the oxygenator. Perfusate halothane levels were maintained in a clinical range. Systolic and diastolic cardiac function were adversely affected by the administration of even low doses of halothane, despite a concomitant increase in coronary blood flow. Because of the immaturity of their calcium transport system, fetal hearts may be particularly sensitive to the known calcium channel-blocking properties of halothane.

Animals

Genitourinary tumors in men with the Muir-Torre syndrome.

The Muir-Torre syndrome is an autosomal dominant genodermatosis characterized by the occurrence of one or more sebaceous gland tumors (either adenoma, epithelioma, or carcinoma) and a single malignant internal neoplasm. To date, 133 cases of Muir-Torre syndrome have been described. Colorectal (49%) and genitourinary (21%) carcinomas are the most common initial neoplasms. The case of a man with a history of recurrent ocular sebaceous carcinoma who subsequently had seminoma is described, and previously published reports of men with Muir-Torre syndrome and genitourinary tumors are discussed. Including this report, an associated genitourinary tumor was the initial malignant internal neoplasm in 11 men with Muir-Torre syndrome. The detection of a genitourinary neoplasm preceded diagnosis of the patient's Muir-Torre syndrome-associated sebaceous gland tumor in five patients (45%). All patients with sebaceous gland tumors of the type associated with Muir-Torre syndrome warrant consideration of Muir-Torre syndrome and appropriate workup to detect asymptomatic malignant visceral neoplasms.

Adenocarcinoma, Sebaceous

Microemboli during coronary artery bypass grafting. Genesis and effect on outcome.

Cerebral dysfunction after coronary artery bypass operations represents some of the most serious and costly complications of cardiac surgery. We used transcranial Doppler ultrasonography to detect and quantify the number of microemboli in the right middle cerebral artery of patients undergoing elective first coronary bypass operations (n = 117) and second coronary bypass operations (n = 10). We hypothesized that total microemboli were related to clinical outcome. A 2 MHz transducer was positioned in front of the ear above the zygomatic arch and depth gated to 50 mm. Microemboli were recorded as perturbations of the blood flow velocity in the middle cerebral artery and aurally monitored. Each episode of microembolism was specified both by clock time and as a perfusion or surgical event. Forty-one patients (32%) completed neuropsychologic evaluation with a battery of tests for cognitive function. Anxiety states and traits were also assessed. The distribution of microembolism showed that there were three groups of patients: < 30 microemboli (n = 83); 30 to 59 (n = 24); and > 60 (n = 20). Seven of 10 patients with cerebral complications (stroke, coma, delirium, aberrant behavior) were in the > 60 microemboli group. Those with cerebral complications had 20.7 +/- 4.5 microemboli from perfusion and 57.4 +/- 15.6 from surgical events. The 13 patients in the > 60 microemboli group without central nervous system symptoms had 95.5 +/- 19.5 microemboli from perfusion and 36.0 +/- 6.9 from surgical events. Neuropsychologic scores were most often depressed for memory (73%), comprehension (49%), attention (46%), and constructional ability (44%). The greatest change was in total score in the > 60 microemboli group (-3.3 +/- 0.6) compared with -1.1 +/- 0.2 and -1.9 +/- 0.2 for the 30 to 59 and < 30 groups, respectively. The incidences of cardiac and pulmonary complications and mortality were different between those patients with < 60 microemboli versus those with > 60 microemboli. Cardiac and pulmonary complications and mortality percentages were 4.7%, 3.7%, and 0.9%, respectively, for the < 60 microemboli group and 20%, 20%, and 15%, respectively, for the > 60 microemboli group. We concluded that transcranial Doppler ultrasonography is a useful technique to quantify and detect the source of microemboli during coronary artery bypass operations and may be useful in assessing new operative strategies, the quality of the perfusion, and potentially as an indicator for pharmacologic therapy in the operating room in patients with high microemboli counts.

Cardiopulmonary Bypass

Balanitis circumscripta plasmacellularis.

Balanitis circumscripta plasmacellularis typically affects the glans penis and/or prepuce, and presents as chronic shiny smooth red-orange plaques. We report on an uncircumcised man with 2 moist red-orange lesions of balanitis circumscripta plasmacellularis on the glans and penile shaft, which were refractory to topical therapy and systemic antibiotics, and review the literature. Clinical morphology, microscopic features, differential diagnosis, postulated etiologies and treatments are discussed. When balanitis circumscripta plasmacellularis is suspected clinically, diagnosis can be readily confirmed by microscopic examination of the lesion. Differentiating this lesion from similar lesions is essential since it is benign and can be treated relatively easily by circumcision.

Aged

Transcranial Doppler sonography. Part 1. Principles, technique, and normal appearances.

Transcranial Doppler sonography is a noninvasive technique that uses a 2-MHz, pulsed Doppler transducer to measure the velocity of blood flow within the circle of Willis and vertebrobasilar system through regions of temporal calvarial thinning or through the orbits or foramen magnum. By using spectral analysis of the Doppler frequency shifts from insonated red blood cells moving through a preselected arterial sample volume, transcranial Doppler calculates and displays the peak systolic and diastolic velocity, the mean velocity, and the pulsatility index of blood flow within the interrogated vessel. Vessel identification is based on standard criteria, including the cranial window used, transducer position, depth of sample volume, direction of blood flow, relationship to the terminal internal carotid artery, and response to common carotid artery compression. Diagnoses made with transcranial Doppler sonography are based on the detection of increased or decreased blood flow velocity, absence of blood flow, or changes in pulsatility.

Blood Flow Velocity

Transcranial Doppler sonography. Part 2. Evaluation of intracranial and extracranial abnormalities and procedural monitoring.

Transcranial Doppler sonography can be used to evaluate a spectrum of intracranial and extracranial vascular abnormalities. It is of proved value in the detection and follow-up of vasoconstriction caused by subarachnoid hemorrhage and can be used to demonstrate significant stenosis or occlusion of basal intracranial arteries and coexisting routes of collateral circulation. Transcranial Doppler sonography can play an important role in the determination of brain death and can be used to identify the nidus of an arteriovenous malformation, along with its major routes of supply and drainage. The technique may provide insights into cerebral hemodynamics following trauma, stroke, or migraine. Use of transcranial Doppler sonography enables a rapid, noninvasive diagnosis of the subclavian steal syndrome, and it is a valuable adjunct to duplex carotid sonography for determining the effect of atherosclerotic lesions of the internal carotid artery on cerebral hemodynamics. In the operating room or angiographic suite, transcranial Doppler sonography can be used to monitor patients undergoing surgical, interventional, or diagnostic procedures for the development of cerebrovascular complications.

Brain Death

Muir-Torre syndrome.

The Muir-Torre syndrome is an autosomal dominantly inherited genodermatosis with malignant potential that is characterized by the presence of at least one sebaceous gland tumor (adenoma, epithelioma, or carcinoma) and a minimum of one internal malignancy. The syndrome has been documented in 147 individuals. Associated features in some of the Muir-Torre syndrome patients are colorectal carcinomas and genitourinary neoplasms. More than half of the 292 visceral cancers described in Muir-Torre syndrome patients were colorectal carcinomas; nearly 60% of these tumors were located at or proximal to the splenic flexure. The presence of even a single Muir-Torre syndrome-associated sebaceous tumor warrants serious consideration for further evaluation of that individual for the syndrome. Therefore, initial and periodic examination for internal malignancy should be performed in individuals with such tumors and patients with the syndrome. Also, family members of Muir-Torre syndrome patients should be screened for Muir-Torre syndrome-associated cutaneous lesions and visceral cancers.

Adenoma