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Biomedical subjects

R Altman

Publications and source records attributed to R Altman.

At least 55 records · Page 3Linked to original sources

Towards a standard query model for sharing decision-support applications.

Many clinical decision-support applications are created in a centralized manner, but distributed widely for local use. When such applications include queries to electronic patient databases, the queries must be translated to conform to local database specifications. Because no well-defined standard model of clinical data exists, the translation process is ad hoc, costly, and error-prone. In this paper, we propose an abstract formalism, called the Standard Query Model Framework, for specifying a standard clinical data model and for supporting the automated and reliable translation of queries that appear in shared decision-support applications. We present the components of this framework, discuss their desirable features, and describe a prototype that we have developed for relational patient databases. We also highlight the outstanding research issues relevant to our approach.

Database Management Systems↗

HIV-related deaths from selected infectious diseases among persons without AIDS in New Jersey.

This study sought to quantify HIV-related deaths among persons not classified as having AIDS, in an area where AIDS incidence among injecting drug users (IDUs) is high. Death certificates of persons who were aged 25-44 years at death, died in 1987 in two New Jersey counties, and had certain infectious conditions were compared with names in the AIDS Registry. Hospital and/or Medical Examiner records were reviewed for nonmatching cases. Cases were considered as confirmed HIV infection if there was laboratory evidence of such infection and as suggestive HIV infection if the decedent had oral thrush or a combination of certain other clinical findings were present. Of 412 deaths meeting the above criteria, 165 (40.0%) were in the AIDS Registry. We investigated 205 of the remainder; of these, 7.3% were found to have AIDS, 21.5% had confirmed HIV infection without AIDS, and 15.1% had suggestive HIV infection. This increased the HIV-related mortality in excess of deaths due to AIDS in this age group by 9.2% for confirmed HIV infections and 15.6% for both confirmed and suggestive HIV infections, with deaths among IDUs increasing 12.3% for confirmed HIV infections and 18.9% for both confirmed and suggestive HIV infections. Thus, in addition to AIDS indicator diseases, a variety of other infectious conditions can lead to death in HIV-infected persons, particularly in IDUs; however, the extent of such deaths may be less than previously described.

Adult↗

Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners.

Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count < or = 0.20 x 10(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects.

Adult↗

Effect of diltiazem and low-dose aspirin on platelet aggregation and ATP release induced by paired agonists.

The authors studied the effects of diltiazem, administered alone and together with low-dose aspirin, on the platelet response to paired agonists. After a baseline period, 25 healthy volunteers were given oral diltiazem for 1 week (120, 240, or 360 mg/day), and then crossed over randomly between 1 week on diltiazem plus aspirin (81 mg/day), and 1 week on aspirin (81 mg/day) alone. Platelet function was tested on 2 consecutive days in each period. Synergistic platelet aggregation and ATP release were obtained at baseline using a subthreshold concentration of arachidonic acid combined with platelet activating factor, ADP, or epinephrine. Diltiazem resulted in significant decrease from baseline in platelet aggregation and ATP release using the arachidonic acid-epinephrine combination (35% and 40% decrease, respectively, p < 0.01) and a significant decrease in aggregation using the arachidonic acid-ADP combination (22% decrease, p < 0.01). The effects were neither dose-related, nor accompanied by any significant change in serum thromboxane B2 levels or bleeding times. There was no significant difference between the effects of aspirin alone and aspirin plus diltiazem on the synergistic platelet aggregation and ATP release induced by the paired agonists, or on thromboxane B2 levels or bleeding times. Diltiazem administered in vivo partially inhibits the synergistic platelet aggregation and ATP release induced by paired agonists; however, in contrast to a previous in vitro study it does not potentiate the platelet-inhibitory effect of aspirin.

Adenosine Diphosphate↗

A systematic comparison of three structure determination methods from NMR data: dependence upon quality and quantity of data.

We have systematically examined how the quality of NMR protein structures depends on (1) the number of NOE distance constraints, (2) their assumed precision, (3) the method of structure calculation and (4) the size of the protein. The test sets of distance constraints have been derived from the crystal structures of crambin (5 kDa) and staphylococcal nuclease (17 kDa). Three methods of structure calculation have been compared: Distance Geometry (DGEOM), Restrained Molecular Dynamics (XPLOR) and the Double Iterated Kalman Filter (DIKF). All three methods can reproduce the general features of the starting structure under all conditions tested. In many instances the apparent precision of the calculated structure (as measured by the RMS dispersion from the average) is greater than its accuracy (as measured by the RMS deviation of the average structure from the starting crystal structure). The global RMS deviations from the reference structures decrease exponentially as the number of constraints is increased, and after using about 30% of all potential constraints, the errors asymptotically approach a limiting value. Increasing the assumed precision of the constraints has the same qualitative effect as increasing the number of constraints. For comparable numbers of constraints/residue, the precision of the calculated structure is less for the larger than for the smaller protein, regardless of the method of calculation. The accuracy of the average structure calculated by Restrained Molecular Dynamics is greater than that of structures obtained by purely geometric methods (DGEOM and DIKF).

Magnetic Resonance Spectroscopy↗

Evaluation of human T cell lymphotropic virus infection in a cohort of injecting drug users.

The diagnosis and confirmation of human T cell lymphotropic virus (HTLV) type II infection has proven difficult, since most assays depend on antigenic cross-reactivity between HTLV-I antigens and HTLV-II antibodies. Type-specific HTLV infection rates were evaluated in a cohort of 233 injecting drug users screened with an HTLV EIA. Of the 52 EIA-reactive specimens, 48 were indeterminate or negative by standard Western blot. Type-specific HTLV results determined by polymerase chain reaction (PCR) were 0, HTLV-I; 92%, HTLV-II; 6%, type indeterminate; and 2%, negative. Among 42 EIA-reactive, HTLV-II-PCR-positive individuals tested by a p21 envr Western blot, all were positive and 74% had antibodies to the tax protein. This study found a high rate (22.3%) of HTLV reactivity, with HTLV-II usually the sole responsible agent; shortcomings in standard HTLV-I-based diagnostics but usefulness of PCR and p21 envr Western blots for typing and confirmation of HTLV reactivity; and a high prevalence (74%) of anti-tax antibody among HTLV-II-seropositive subjects, suggesting increased potential for infectivity.

Cohort Studies↗

Premarital HIV-1 testing in New Jersey.

To answer questions related to the usefulness of premarital testing for human immunodeficiency virus type 1 (HIV-1), two "blinded" or "nonlinked" HIV-1 serosurveys were done in New Jersey, a state with a high incidence of AIDS, on blood specimens submitted for a premarital serologic test for syphilis. The first survey involved premarital blood specimens submitted to the New Jersey Department of Health laboratory for the year starting September 1987. The second survey involved premarital specimens submitted to five private or hospital clinical laboratories in the spring of 1989, of which approximately 1,000 consecutive premarital specimens from each laboratory were sent to the Department of Health laboratory for HIV-1 testing. Of 4,247 specimens tested in the 1987-1988 survey, 21 (0.49%) were positive for antibodies to HIV-1, while among 4,696 specimens in the 1989 survey, 29 (0.62%) were positive. When the survey results were weighted by the number of marriages by geographic regions of the state, the weighted premarital HIV-1 seroprevalence was 0.55% for the 1987-1988 survey and 0.62% for the 1989 survey. The male/female ratio of positive tests was 2.7:1 in 1987-1988 and 1.6:1 in 1989. Of the 8,943 specimens in both surveys, 5 (0.06%) gave an indeterminate immunoblot result, compared with 50 positive results. These percentages of premarital HIV-1 infections are much higher than earlier estimates and reports and are of the same magnitude as recently reported blinded premarital HIV-1 testing elsewhere. Results of this magnitude support a recommendation in New Jersey of voluntary HIV-1 counseling and testing for marriage applicants.

Adult↗

The solution structures of Escherichia coli trp repressor and trp aporepressor at an intermediate resolution.

We have determined the solution structures and examined the dynamics of the Escherichia coli trp repressor (a 25-kDa dimer), with and without the co-repressor L-tryptophan, from NMR data. This is the largest protein structure thus far determined by NMR. To obtain a set of data sufficient for a structure determination it was essential to resort to isotopic spectral editing. Line broadening observed in this molecular mass range precludes for the most part the measurement of coupling constants and stereospecific assignments, with the inevitable result that the attainable resolution of the final structure will be somewhat lower than the resolution reported for smaller proteins and peptides. Nevertheless the general topology of the protein can be deduced from the subsets of NOEs defining the secondary and tertiary structure, providing a basis for further refinement using the full set of NOEs and energy minimization. We report here (a) an intermediate resolution structure that can be deduced from NMR data, covalent, angular and van-der-Waals constraints only, without resort to detailed energy calculations, and (b) the limits of uncertainty within which this structure is valid. An examination of these structures combined with backbone amide exchange data shows that even at this resolution three important conclusions can be drawn: (a) the protein structure changes upon binding tryptophan; (b) the putative DNA binding region is much more flexible than the core of the molecule, with backbone amide proton exchange rates 1000 times faster than in the core; (c) the binding of tryptophan stabilizes the repressor molecule, which is reflected in both the appearance of additional NOEs, and in the slowing of backbone proton exchange rates by factors of 3-10. Sequence-specific 1H-NMR assignments and the secondary structure of the holopressor (L-tryptophan-bound form) have been reported previously [C. H. Arrowsmith, R. Pachter, R. B. Altman, S. B. Iyer & O. Jardetzky (1990) Biochemistry 29, 6332-6341]. Those for the trp aporepressor (L-tryptophan-free form), made using the same methods and conditions as described in the cited paper, are reported here. The secondary structure of the aporepressor was calculated from sequential and medium-range NOEs and is the same as reported for the holorepressor except that helix E is shorter. The tertiary solution structures for both forms of the repressor were calculated from long-range NOE data.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip.

Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.

Hip Joint↗

Double-blind comparison of cetirizine and placebo in the treatment of seasonal rhinitis.

The efficacy and safety of cetirizine were evaluated in 419 patients with seasonal allergic rhinitis. Using a 4-way, double-blind randomization schedule, patients were given a 1-week course of once daily cetirizine (5, 10, or 20 mg) or placebo. Patient and physician efficacy ratings corresponded, indicating superiority of cetirizine to placebo (P less than .05) in reducing symptom severity scores for sneezing, rhinorrhea, ocular pruritus, nasal pruritus, watering of the eyes, and redness of the eyes. All cetirizine doses achieved higher efficacy ratings (72.7%, 79.2%, and 75.7%, respectively) than placebo (52.9%; P less than .05) by the physician's global assessment. Cetirizine was well tolerated, with sedation being the most common adverse experience, increasing in frequency at higher doses. A dose-response relationship was evident for selected symptoms, and the once daily 5-mg dose was found to be an effective minimum dose.

Adult↗

Comparison of two levels of anticoagulant therapy in patients with substitute heart valves.

After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.

Acenocoumarol↗

The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand.

Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands.

Adult↗

Exposure factors for HIV-1 infection among heterosexual drug abusers in New Jersey treatment programs.

In a cross-sectional study of 926 subjects from 10 drug treatment programs conducted in 1984 in New Jersey, the seroprevalence of human immunodeficiency virus (HIV) was 35% overall; 30% in whites, 33% in hispanics, and 46% in blacks (p = 0.01 for comparison of blacks to non-blacks). Univariate analysis showed the seroprevalence of HIV was not associated with age or gender, but did correlate with frequency of cocaine or heroin injection (p trend less than 0.001); frequency of needle sharing (p trend = 0.007); and inversely with levels of education (p = 0.05). The prevalence of HIV was also inversely related to the distance of the treatment center from lower Manhattan; being highest for distances of less than 5 miles from lower Manhattan and lowest for distances of 80 miles, with intermediate rates for the intervening distances (p trend less than 0.001). In multivariate analyses, HIV seropositivity was consistently associated with the frequency of needle sharing (p = 0.02) and less than 12 years (high school level) of education (p = 0.02), but not with black race. However, blacks who shared needles less than once a month had a relative risk of 3.2 (95% CI 1.2, 7.7) while non-blacks who shared less than once a month had a relative risk of only 0.9 (95% CI 0.3, 2.4). The risk in non-blacks increased to more than twofold with more frequent needle sharing. When the analysis was stratified by gender and adjusted for needle sharing and geography, a significant twofold increased risk was observed for female (but not male) subjects who had two or more heterosexual partners compared with those who had one partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Community-based perinatal research.

A program of clinical perinatal research was established in a community-based hospital in collaboration with private-practice obstetricians and their patients. This longitudinal study, undertaken to investigate the value of a circulating placental protein as an indicator of fetal compromise, enrolled 200 unselected pregnant patients. The project required collection of five blood samples at 16, 20, 24, 28, and 32 weeks' gestation in addition to a level II ultrasound examination at 32 weeks. Baseline and interim prenatal visit data were collected, as were maternal and neonatal data upon delivery. Patients who participated were invariably enthusiastic about their involvement. The physicians and their staff were also generally pleased. We infer from these and other studies a need to provide enhanced educational, participatory opportunities to all pregnant women. We conclude that properly conducted, reasonably funded projects that offer no direct benefit to the patient or physician can be successfully carried out with physicians and their private patients in community hospitals. The potential benefits of developing such extended resources can only enhance medical care and foster satisfaction and cooperation among physicians and patients.

Attitude of Health Personnel↗

Why single daily dose of aspirin may not prevent platelet aggregation.

The effect of different doses of aspirin on the synergistic activity of sodium arachidonate plus platelet activating factor (paf) ADP or collagen in platelet aggregation was studied in human volunteers. Aggregation studies in platelet rich plasma (PRP) showed that aspirinated platelets, unresponsive to arachidonate, when stirred with threshold concentrations of paf, ADP or collagen, reacted differently according to the dose of aspirin and the time elapsed since ingestion. After a single or daily 50 mg dose for 7-10 days independent of elapsed time until blood withdrawal, a complete synergistic activity was obtained. In PRP samples obtained 24 hours after the last aspirin intake, a complete synergistic aggregation was achieved after a single dose or after 7-10 days of 500 mg aspirin ingestion; synergistic effect did not appear when blood was drawn 2.5 hours after intake. The thromboxane B2 concentrations were very low in all samples after PRP stimulation with sodium arachidonate or paf or both. As rationale is that platelet activation in vivo occurs in response to several stimuli, the therapeutic implications of our results is that aspirin may not prevent the agonist potentiation effect when low dose or daily high dose (500mg) are administrated. This may explain the erratic results of most aspirin trials in which this drug was used to suppress platelet function.

Adult↗

Segregation of lymphocyte low-molecular-weight DNA and antinuclear-antibodies in a family with systemic lupus erythematosus in first cousins.

All patients with systemic lupus erythematosus (SLE) demonstrated two classes of newly synthesized DNA in sucrose density gradients of PHA (phytohemagglutinin)-stimulated lymphocytes: a large-molecular-weight fraction that comigrates with control DNA and an excess low-molecular-weight DNA (LMW-DNA) fraction not found in control lymphocytes. Excess LMW-DNA was independent of disease activity or drug therapy. LMW-DNA and serologic abnormalities were studied in a four-generation family in which two first cousins had SLE. Excess LMW-DNA was found in the cousins with SLE, sibling parents of the SLE patients, a common grandparent, four of nine siblings of one patient, and five of seven at risk children. Both males and females had excess LMW-DNA. Male-male transmission was observed. The expression of excess LMW-DNA in stimulated lymphocytes is inherited as an autosomal dominant genetic trait in this family. All unaffected adult family members with the marker had positive antinuclear antibodies (ANAs) except the grandmother. However, none of the five children with excess LMW-DNA showed positive ANAs. Excess LMW-DNA precedes the appearance of ANAs when found in children of adults with excess LMW-DNA, and may be a predisposing factor in the development of the immunologic responses of systemic lupus erythematosus.

Antibodies, Antinuclear↗

Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation.

Platelet aggregation in vivo occurs through the combined effects of many agonists. Aspirin inhibits platelet aggregation but its antiaggregate effects can be overcome by the synergistic action of sodium arachidonate (AA) plus platelet activating factor (PAF). We tested the effect of a calcium entry-blocking agent, diltiazem, on AA-PAF-induced platelet aggregation in platelet-rich plasma from seven healthy volunteers. The studies were done before and after aspirin (100 mg/day) administration for 7 to 10 days. Stimulation of platelet was done in vitro by AA, PAF, or both. Before aspirin treatment, diltiazem (2 micrograms/ml) added in vitro to the platelet-rich plasma inhibited platelet aggregation induced by AA (0.75 mmol/L) by 50%. When PAF was used the inhibition of aggregation was obtained at a lower concentration of diltiazem (0.4 to 1 microgram/ml). After aspirin treatment, AA-induced aggregation was inhibited, and PAF alone (30 nmol/L) produced a first-wave aggregation followed by complete disaggregation. When AA and PAF were added together a full aggregation of postaspirin treatment platelets was obtained. Diltiazem added in vitro at the clinically attainable concentration of 0.1 microgram/ml produced a complete inhibition of this AA-PAF synergism on platelet aggregation. These results suggest that administration of a combination of low-dose aspirin and diltiazem may be of greater benefit than aspirin alone for prophylaxis of cardiovascular diseases where platelets are involved in the pathogenesis.

Arachidonic Acids↗