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Biomedical subjects

J Jacobson

Publications and source records attributed to J Jacobson.

At least 55 records · Page 3Linked to original sources

BANTER: a Bayesian network tutoring shell.

We present an educational tool for bringing the information contained in a Bayesian network to the end user in an easily intelligible form. The BANTER shell is designed to tutor users in evaluation of hypotheses and selection of optimal diagnostic procedures. BANTER can be used with any Bayesian network containing nodes that can be classified into hypotheses, observations, and diagnostic procedures. The system enables one to present various types of queries to the network, to test one's ability to select optimal diagnostic procedures, and the request explanations. We describe the system's capabilities by illustrating how it functions with two structurally different network models of real-world medical problems.

Adult↗

Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B.

Loss of heterozygosity (LOH) involving 3p occurs in many carcinomas but is complicated by the identification of four distinct homozygous deletion regions. One putative target, 3p14.2, contains the common fragile site, FRA3B, a hereditary renal carcinoma-associated 3;8 translocation and the candidate tumor suppressor gene, FHIT. Using a approximately 300 kb comsid/lambda contig, we identified homozygous deletions in cervix, breast, lung and colorectal carcinoma cell lines. The smallest deletion (CC19) was shown not to involve FHIT coding exons and no DNA sequence alterations were present in the transcript. We also detected discontinuous deletions as well as deletions in non-tumor DNAs, suggesting that FHIT is not a selective target. Further, we demonstrate that some reported FHIT aberrations represent normal splicing variation. DNA sequence analysis of 110 kb demonstrated that the region is high in A-T content, LINEs and MER repeats, whereas Alu elements are reduced. We note an intriguing similarity in repeat sequence composition between FRA3B and a 152 kb segment from the Fragile-X region. We also identified similarity between a FRA3B segment and a small polydispersed circular DNA. In contrast to the selective loss of a tumor suppressor gene, we propose an alternative hypothesis, that some putative targets including FRA3B may undergo loss as a consequence of genomic instability. This instability is not due to DNA mismatch repair deficiency, but may correlate in part with p53 inactivation.

Acid Anhydride Hydrolases↗

Evolving stages of lipohemarthrosis of the knee. Sequential magnetic resonance imaging findings in cadavers with clinical correlation.

RATIONALE AND OBJECTIVES: Lipohemarthrosis, the presence of fat and blood in a joint cavity, exhibits several complex layers related to differences in specific component relaxation on magnetic resonance (MR) images. The authors investigated sequential changes in the appearance of lipohemarthrosis of the knee as demonstrated by MR imaging. METHODS: Sequential MR imaging over a 4-day period was performed on two cadaveric knees after intraarticular injection of blood from a volunteer and fat from a cadaveric tibia (50 mL of blood and 25 mL of fat in one knee and 15 mL of blood and 5 mL of fat in the other knee). The authors determined components in the joint based on MR signal behavior. Magnetic resonance imaging examinations of four patients with intracapsular fractures and lipohemarthroses of the knee were reviewed retrospectively. RESULTS: Sequential MR images of cadaveric knees showed serial changes representing progressive formation and lysis of blood clot. Several fluid-fluid levels (globules of fat at the interface between fat and blood) and entrapment of fat were early findings of lipohemarthrosis. Three different fluid levels appeared approximately 3 hours after injection of fresh blood and marrow fat. The 96-hour study demonstrated three distinct levels. CONCLUSIONS: Lipohemarthrosis demonstrates temporal changes on MR imaging related to stages of formation and lysis of blood clot.

Adult↗

Collateral ligaments of the elbow: conventional MR imaging and MR arthrography with coronal oblique plane and elbow flexion.

PURPOSE: To determine the best plane and position of the elbow for optimal visualization of normal and abnormal collateral ligaments with conventional magnetic resonance (MR) imaging and MR arthrography, to determine the normal appearance of the collateral ligaments at MR arthrography and to assess use of MR arthrography in evaluation of collateral ligamentous lesions. MATERIALS AND METHODS: Nine cadaveric elbow specimens were imaged with and without intraarticular administration of gadolinium-containing solution in several planes that were identified as potentially useful in a pilot study in two specimens. MR imaging findings were compared with anatomic findings. RESULTS: Normal and abnormal ligaments were best depicted in a 20 degrees posterior oblique coronal plane in relation to the humeral shaft with the elbows extended and a coronal plane aligned with the humeral shaft with the elbows slightly flexed (20 degrees-30 degrees of flexion). Gadolinium enhancement improved the delineation of normal and abnormal ligaments on T1-weighted images in each case. CONCLUSION: The posterior oblique coronal plane with the elbows extended or the coronal plane aligned with the humeral shaft with the elbows slightly flexed allows accurate assessment of the collateral ligaments. Gadolinium-enhanced MR arthrography of the elbow seems to be a promising technique.

Aged↗

Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study.

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.

Adenocarcinoma↗

Increased mortality of older patients with acute respiratory distress syndrome.

OBJECTIVE: To examine the relationship between age and mortality in ARDS patients and evaluate the importance of factors that increase the mortality of older ARDS patients. DESIGN: Prospective inception cohort study. SETTING: Community-based referral hospital. PATIENTS: Two hundred fifty-six ARDS patients identified from May 1987 to December 1990. ARDS was defined by the following: (1) PaO2/PAO2 < or = 0.2; (2) pulmonary capillary wedge pressure < or = 15 mm Hg; (3) total static thoracic compliance < or = 50 mL/cm H2O; (4) bilateral infiltrates on chest radiograph; and (5) an appropriate clinical setting for ARDS. MAIN OUTCOME MEASURES: Comparison of organ failure, incidence of sepsis, patient demographics, arterial oxygenation, and level of support in those 55 years and younger and those older than 55 years of age. Withdrawal of support in patients who died. RESULTS: Seventy-two of 112 patients older than 55 years (64%) died vs 65 of 144 patients 55 years and younger (45%) (p = 0.002). Examination of patient groups using age identified older than 55 years as a "cutpoint" above which mortality was greater (p = 0.002). Older nonsurvivors did not differ from nonsurvivors 55 years or younger with respect to gender, smoking history, ARDS risk factors, ARDS identifying characteristics, APACHE II (acute physiology and chronic health evaluation), number of organ failures, or the incidence of sepsis. In the 48 h prior to death, nonsurvivors 55 years and younger had more organ failure (3.4 +/- 0.2 vs 2.8 +/- 0.2; p = 0.03), higher fraction of inspired oxygen (0.82 +/- 0.03 vs 0.68 +/- 0.03; p = 0.008), and higher positive end-expiratory pressure levels (13 +/- 1 vs 8 +/- 1; p = 0.001) than older nonsurvivors. Despite more severe expression of disease, only 32 (50%) nonsurvivors 55 years and younger had support withdrawn. Significantly more nonsurvivors older than 55 years (73%) had support withdrawn (p = 0.009). Even in the absence of chronic disease states, withdrawal was more likely for patients older than 55 years (21/51) than in those 55 years and younger (3/32; p < 0.001). CONCLUSIONS: Mortality is significantly higher for patients with ARDS older than 55 years. Decisions to withdraw support are made more often in ARDS patients older than 55 years. These data suggest that age bias may influence decisions to withdraw support.

APACHE↗

A double-blind randomized study of the treatment of endometriosis with nafarelin or nafarelin plus norethisterone.

The objective of this study was to compare the efficacy of nafarelin 200 micrograms (Group A), nafarelin 400 micrograms (Group B) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg (Group C) daily, in treating symptoms of endometriosis, American Fertility Society score and adverse events during 6 months of treatment. A prospective, randomized, double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included. The patients were seen monthly for physical examination and records were taken for bleeding pattern, symptom score and adverse events. A control laparoscopy was performed at the end of 6 months of treatment. All patients were followed 6 months after treatment. At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups. The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C, but during the rest of treatment there were no differences between the groups. Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily, and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control.

Adult↗

Spatiotemporal stationarity of epileptic focal activity evaluated by analyzing magnetoencephalographic (MEG) data and the theoretical implications.

BACKGROUND: The emitted brain neuromagnetic activity was recorded from patients suffering from idiopathic epilepsy, using a Superconductive Quantum Interference Device (SQUID). This activity will be referred as magnetoencephalogram (MEG). METHODS: The MEG recording which were obtained from 32 equal spaced points of a rectangular 4 x 8 matrix were analysed using Fourier statistical analysis. Then, a two dimensional brain mapping technique was utilized in order to detect the possible existence and the accurate localization of epileptic foci. The applied technique was based on the construction of ISO contour maps which are lines of equal power spectral amplitudes of the scalp spatial distribution of the recorded MEGs specific frequency bands. These maps will be referred as ISO-SA maps. A number of more than 200 epileptic patients were examined using this method. For each patient the magnetic brain activity was recorded for the temporal lobes, the frontal lobe and the occipital lobe. ISO-SA mappings were reconstructed for the frequency bands of the compound delta and theta rhythms (2-7 Hz), the alpha rhythm (8-13 Hz), and the beta rhythm (14-25 Hz). In these mappings epileptic (pathological) foci are represented as points emitting abnormal high magnetic power in the frequency band of 2-7 Hz. RESULTS: Systematic MEG measurements showed that the abnormal activity of a certain cortex region, when present, is stationary, i.e., time-invariant. CONCLUSIONS: Brain magnetic fields on the order of magnitude a picotesia are considered as to their possible physiologic nature, and a query is made as to what physical mechanisms might be involved in this propitiation.

Epilepsies, Partial↗

Evaluation of multimodality treatment of locoregional esophageal carcinoma by Southwest Oncology Group 9060.

BACKGROUND: Continuous infusion 5-fluorouracil (CI5-FU) has been utilized concurrently with radiotherapy to improve tumor control. In this pilot trial, cisplatin, CI5FU, and radiotherapy were utilized for the treatment of locoregional esophageal carcinoma. It was postulated that the combination would be well tolerated and associated with high response rate and survival duration. METHODS: Thirty-two eligible patients with locoregional squamous cell carcinoma and adenocarcinoma of the esophagus received a regimen consisting of the following: radiotherapy, 50 Gray (Gy) (30 Gy anteroposterior/posteroanterior regional with 20 Gy AP/LPO/RPO boost) over 5 weeks, with CI5-FU 250 mg/m2/d for the duration of radiotherapy and cisplatin 25 mg/m2/day on Days 1-3 during Weeks 1 and 4 of the radiotherapy cycle. Upon completion of radiotherapy, two additional course, of cisplatin 75 mg/m2 on Days 1 and 29 and CI5-FU 300 mg/m2/day on Days 1-21 and 29-50 were delivered. Following imaging and endoscopic reassessment, patients with no evidence of disease received more chemotherapy. Surgery was suggested only for patients with residual local disease. RESULTS: Complete response was demonstrated in 44% of patients, clinically in 12 patients, and during surgery in 2 others. The median survival was 20 months, and the 1-year survival rate was 59%. Toxicity was severe, comprised of esophagitis, infection, and gastrointestinal complications. Dose delays and reductions occurred in the majority of patients. Four early deaths were noted. CONCLUSIONS: The regimen that was the focus of this trial has been active in the treatment of esophageal carcinoma. However, compared with existing regimens, its complexity and toxicity preclude its future use without modifications.

Adenocarcinoma↗

Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors.

BACKGROUND: This study was conducted to determine the feasibility of, and improve outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue. METHODS: Fifty-four newly diagnosed patients received 7 cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation therapy after the fifth chemotherapy cycle was the primary approach to local control. RESULTS: Actuarial 5-year event-free survival (EFS) and overall survival rates were 42% and 45%, respectively, with a median duration of potential follow-up of 6.8 years. EFS was significantly better for patients with localized tumors than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local progression-free survival at 5 years was 74%, and did not correlate with primary tumor size or site, histologic subtype, or the presence of metastases. Febrile neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac dysfunction was common (7% and 40% respectively). There were four toxic deaths and one case of secondary myelodysplastic syndrome. CONCLUSIONS: Despite substantial toxicity, the integration of IE into the front-line, VAdriaC-based therapy of patients with Ewing's sarcoma family of tumors is feasible and appeared to significantly improve the outcome for patients with high risk localized tumors, but had no impact on the poor prognosis of patients with metastatic tumors. Local control can be achieved in the vast majority of patients using radiotherapy exclusively, even among patients with bulky, central axis tumors. Longer follow-up is needed to evaluate the late effects of this intensive therapy.

Adolescent↗

Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer.

We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated.

Antineoplastic Combined Chemotherapy Protocols↗

Consistency of repeated event-related potentials in clinically stable HIV-1-infected drug users.

This study investigated the stability over time of delays in auditory event-related potentials (ERPs) caused by HIV-1 infection of the brain. ERPs were recorded at two time points from 17 former parenteral drug users (PDUs) and 8 non-PDU control subjects. There was no significant effect of time, and peak measures for the two visits were significantly correlated with each other. For both visits, N1 was delayed only for the seropositive stage IV subjects, whereas N2 was delayed for both seropositive groups. Group differences remained stable, confirming previously reported studies.

Acoustic Stimulation↗

Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy.

PURPOSE: To evaluate whether recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. PATIENTS AND METHODS: Thirty-seven newly diagnosed patients age 1 to 25 years were randomized to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 micrograms/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was > or = 500/microliter on 2 consecutive days. RESULTS: GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P < .0001), but did not significantly affect the grade of granulocyte nadir. No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival. GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/microliter [range, 3,000 to 288,000] v 59,000/microliter [range, 3,000 to 309,000], P < .0001; median time to recovery > 75,000/microliter, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P < .0001). CONCLUSION: GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity.

Adolescent↗

The assessment of neurobehavioral toxicity: SGOMSEC joint report.

Exposure to neurobehavioral toxicants is a problem of international scope. Although many different procedures are available for the assessment of human behavioral function, performance tests are displacing traditional diagnostic tests for ascertaining the consequences of exposure to neurotoxic chemicals. Performance testing includes variables such as attention and concentration, sensory function, motor control, spatial relations, visuomotor coordination, memory, and affect. Special tests have also been devised for evaluating child development. One of the salient needs in these efforts is the construction of databases allowing access to normative data.

Adult↗

Detecting risk drinking during pregnancy: a comparison of four screening questionnaires.

OBJECTIVES: This study investigated the efficacy of screening for risk drinking during pregnancy with two brief questionnaires, TWEAK and T-ACE. Both include an assessment of tolerance based on the number of drinks women report they can hold. METHODS: Subjects were disadvantaged African-American obstetric patients in Detroit, Mich. Traditional alcoholism screens (Michigan Alcohol Screening Test [MAST], CAGE) and the tolerance question were administered (n = 2717); TWEAK and T-ACE were constructed from tolerance and embedded MAST and CAGE items. In a separate sample (n = 1420), only the T-ACE was administered. Periconceptional risk drinking was the gold standard. Screen evaluations were based on receiver-operating characteristic analyses. RESULTS: At the cutpoint of 2, sensitivity/specificity for embedded screens were 91/77 for TWEAK and 88/79 for T-ACE; comparable values for T-ACE alone were 67/86. TWEAK and T-ACE screened more effectively than CAGE or MAST. CONCLUSIONS: Embedded versions of TWEAK and T-ACE were both highly sensitive to periconceptional risk drinking in this population. Administering T-ACE alone reduced its sensitivity; this suggests that MAST and CAGE administration improves its performance.

Adult↗

Characteristics of children and adolescents with mental retardation and frequent outwardly directed aggressive behavior.

Two interrelated cross-sectional studies were conducted to expand earlier findings about correlates of outwardly directed aggressive behavior in children with mental retardation. In Study 1 we compared children with mental retardation, 27 with and 23 without aggression. Aggression was best predicted by concurrent self-injurious behavior (SIB). In Study 2 we examined the likelihood that aggression was predicted by concurrent SIB and other nondestructive maladaptive behaviors in an archival cohort of 701 children younger than 21 with IQs below 70. Self-injurious behavior significantly predicted outwardly directed aggression for all children regardless of age. Additional predictors besides SIB showed only minimal improvements in model R2 values. Results were discussed in light of recent research proposing a common basis for aggression and SIB.

Adolescent↗