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Biomedical subjects

J Jacobson

Publications and source records attributed to J Jacobson.

At least 37 records · Page 2Linked to original sources

Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009.

Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56+ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0. 001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8+ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA and VLA4+ cells and minimal increases in CD56+ and CD25+ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25+, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.

Adjuvants, Immunologic↗

Readmission after cardiac operations: prevalence, patterns, and predisposing factors.

OBJECTIVES: This study was undertaken (1) to determine the prevalence of hospital readmission within 1 month of discharge after cardiac operations, (2) to categorize diagnoses responsible for readmission, and (3) to examine predischarge patient factors that influenced readmission. METHODS: Data at 1 month after discharge were obtained for 1665 (98.4%) of 1692 patients who underwent cardiac operations between January 1996 and July 1998. RESULTS: Two hundred twenty-five patients (13.5%) were readmitted to a hospital within a 1-month period after discharge. Forty-eight percent of readmissions were to other hospitals. The most common readmission problems were congestive heart failure (15.6%), atrial fibrillation (12.9%), chest pain (12.0%), wound problems (10.2%), and gastrointestinal problems (8.0%). Hospital discharge on or before the fifth postoperative day was associated with a lower prevalence of subsequent readmission. The independent predictors of a readmission for congestive heart failure were postoperative stay longer than 5 days, diabetes, New York Heart Association functional class IV, preoperative congestive heart failure, total blood product use, the need for postoperative inotropes, body mass index greater than 28 kg/m(2), and reoperation for bleeding. CONCLUSIONS: The prevalence of rehospitalization during the first month after discharge is not trivial. Other than postoperative atrial fibrillation, readmission is probably the single most likely adverse event to befall a patient in the early postoperative period. Patients who are discharged early do not appear to be at increased risk. Patterns in readmission diagnoses suggest opportunities for preventive strategies.

Aged↗

Ultrasound diagnosis and surgical pathology of the torn interosseous membrane in forearm fractures/dislocations.

Ultrasound was used to effectively diagnose and precisely locate a torn interosseous membrane in 2 forearm fracture/dislocations. The ultrasound appearance of the torn interosseous membrane in cadavers and in the fractures/dislocations shows disruption of the anterior and posterior layers in midsubstance or adjacent to the radius or ulna. The surgical pathology in 3 forearm fractures/dislocations (2 Galeazzi injuries and 1 Essex-Lopresti injury) shows a longitudinal oblique tear of the interosseous membrane, parallel to its major palmar fibers, oriented from proximal radial to the distal ulnar. After ultrasound diagnosis, we demonstrated the feasibility of direct primary repair of the torn interosseous membrane associated with the Essex-Lopresti injury in a clinical case.

Adult↗

Modeling the involvement of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in autoimmune and stress-related rheumatic syndromes in women.

Autoimmune and stress-related rheumatic diseases are significantly more common in women than in men. Our group has focused on the role of two principal neuroendocrine axes, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, in this increased susceptibility to rheumatic disease. We review the physiology of the HPA and HPG axes and discuss their reciprocal interactions. Mechanisms by which hormones of the HPA and HPG axes influence the immune system and modulate the course of autoimmune inflammatory diseases in animal models of rheumatic disease are described. In addition, we review the data suggesting the importance of these neurohormonal systems in rheumatic diseases. These data provide insights into why women may be at increased risk and how we might better understand the mechanisms that provoke expression of rheumatic diseases in women. To advance research in this area, it is critical to develop methods to evaluate the function of the neuroendocrine axes. Secretion of both HPA and HPG axis hormones, particularly the hormones of the hypothalamus and anterior pituitary, is largely by intermittent pulses. In addition, the HPA axis exhibits a profound circadian, or near 24-hour, variation, and HPG axis hormones fluctuate over the monthly cycle. These factors make meaningful analysis of these axes quite complex. We discuss models used in the analyses of neuroendocrine axes and the use of challenge testing to assess the integrity of neuroendocrine axes.

Animals↗

Inclusion of black Americans in oncology clinical trials: the Louisiana State University Medical Center experience.

Recruitment of patients from diverse ethnic, racial, and socioeconomic backgrounds for clinical trials is desirable for both scientific and ethical reasons. Participation rates in clinical trials are low for minorities and especially for black Americans. This report summarizes the experience at Louisiana State University Medical Center in Shreveport, Louisiana, in enrolling black Americans in oncology treatment and prevention trials. Barriers to enrollment are identified and discussed. Although major strides must still be made in the area of cancer prevention, the university's experience demonstrates that black Americans can be encouraged to participate in and can be enrolled in cancer clinical trials.

Black or African American↗

Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients.

This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated Mycobacterium avium complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study. Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups. Microbiological responses were comparable, with mean decreases of 1. 5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively. Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity. Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load.

AIDS-Related Opportunistic Infections↗

Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial.

OBJECT: Sedation regimens for head-injured patients are quite variable. The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used. METHODS: Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95+/-87 hours) and 19 patients in the morphine group (mean time of morphine usage 70+/-54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events. CONCLUSIONS: Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.

Adult↗

Relationship between health promotion lifestyle profiles and patient outcomes of biofeedback therapy for urinary incontinence.

Computerized EMG biofeedback therapy is a conservative treatment option for patients with urge incontinence, frequency, and certain types of stress urinary incontinence. Patient motivation to follow through with treatment and home exercise program is an important factor for successful therapy. The Health Promotion Lifestyle Profile (HPLP) II measures the frequency of health-promoting behaviors. A preliminary study of 45 patients suggested the HPLP II is a valid and reliable predictor of patient motivation. Further research is needed to ascertain if the tool may serve to predict patients' commitment to biofeedback and subsequent success with therapy. Effective screening of patients can also reduce overuse of services and ensure appropriate use of percapitated dollars.

Adult↗

Selection of local therapy after neoadjuvant chemotherapy in patients with stage IIIA,B breast cancer.

BACKGROUND: Stage IIIA,B breast cancer is commonly treated with neoadjuvant chemotherapy because of high objective response rates and improved operability. Criteria for subsequent selection of local therapy--mastectomy, radiotherapy, or both--are not well defined. We adopted a policy of selective local therapy based on rebiopsy of the breast and clinical axillary lymph node status at the time of best response to chemotherapy. METHODS: Between 1980 and 1993, 126 patients with stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and definitive local therapy. The long-term incidence of locoregional failure (in-breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and overall survival was determined. RESULTS: The overall clinical objective response rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with negative margins achieved in 91.6%. Forty-two patients had breast preservation; the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients), axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76 patients) for clinically negative axilla treated with radiotherapy only, and 12.0% (6 of 50 patients) for clinically positive axilla treated with surgery only. The overall long-term survival probabilities (6 years) according to stage were: stage IIIA-58.0%, stage IIIB(noninflam)-58.0%, stage IIIB(inflam)-36.0%. CONCLUSIONS: These findings support a selective approach to local therapy in patients with stage IIIA,B breast cancer. This approach provides local control in most patients, and allows for breast preservation and elimination of axillary dissection in selected patients.

Adult↗

Maternal and neonatal outcome following prolonged labor induction.

OBJECTIVE: To examine the effect of labor induction length on maternal and neonatal outcome. METHODS: Inductions of labor were reviewed retrospectively, comparing 27 patients with infectious complications to 313 with no infections. Univariate analysis, t-test, chi2, and Fisher exact test were used for statistical analysis. Forward stepping logistic regression was used in a multivariate model to identify odds ratio (OR) and 95% confidence intervals (CI). RESULTS: There was a statistically significant increased risk of maternal infection with increasing induction time. In univariate analysis, cesarean delivery, duration of induction, duration of oxytocin administration, nulliparity, use of internal monitors, increased maternal weight gain, and low cervical dilatation at start of induction were all associated with increased maternal infection risk. Multivariate analysis showed duration of induction for each additional 2 hours (OR 1.09; 95% CI 1.01, 1.18) and nonwhite ethnicity (OR 5.95; 95% CI 1.72, 20.49) to be associated significantly with maternal infection. Maternal infection was associated with lower Apgar scores and increased neonatal intensive care unit admissions. In patients who delivered vaginally, a logistic regression model estimated infectious morbidity at 40 hours to be 10%. The cesarean rate was not increased with prolonged induction. CONCLUSION: Prolonged induction is associated with a small increased risk of infectious morbidity, with an estimated 10% incidence noted after 40 hours of induction in women who deliver vaginally.

Adult↗

Phase II trial of oral beta-all trans-retinoic acid in hepatocellular carcinoma (SWOG 9157).

Twenty-nine chemotherapy-naive patients with primary hepatocellular carcinoma were treated with oral beta-all trans-retinoic acid (retinoic acid, TRA 50 mg/m2 t.i.d.) on a 3-week on/one week off schedule until progression or grade 3 or 4 toxicity. Eligibility requirements allowed abnormal liver function tests as long as the creatinine and bilirubin levels were normal. No responses were seen and the median survival was four months. Grade 3 side effects occurred in II patients and grade 4 in four and included a wide range of toxicities. The results indicate that oral TRA is ineffective against primary hepatocellular carcinoma and suggest that dose-modification of this retinoid may be required in patients with significant malignant hepatic involvement.

Administration, Oral↗

Telomerase activity in the differentiation of benign and malignant adrenal tumors.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that extends the ends of chromosomes by synthesizing the 6 oligonucleotide repeat TTAGGG and thus serves as a marker for cellular immortality. Although absent in most adult somatic tissues, telomerase activity is present in stem cells and is reactivated in nearly all primary human malignancies. In this study we sought to determine whether tumors of the adrenal glands contain telomerase activity and whether telomerase activity can be used to differentiate benign and malignant tumors of the adrenal glands. METHODS: Tissue was obtained from 23 specimens at adrenalectomy. Adjacent normal adrenal tissue was obtained for control. All specimens were rapidly frozen and stored at -80 degrees C until assay. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was present in 5 of 23 (22%) of the adrenal tumors. All 3 malignant tumors were strongly TRAP positive. There was a single cortical adenoma that had very weak telomerase activity. The single TRAP-positive tumor of the adrenal medulla was a ganglioneuroma. CONCLUSIONS: Benign adrenal tumors infrequently contain telomerase activity, whereas telomerase reactivation appears to be common in malignant tumors of the adrenal glands. These data suggest that determination of telomerase activity may offer a novel way to facilitate the differentiation of benign and malignant adrenal tumors.

Adrenal Gland Neoplasms↗

Inadequate documentation and resection for gastric cancer in the United States: a preliminary report.

Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016 (SWOG 9008) after a "curative" gastric resection were assessed to determine practice patterns of more than 300 surgeons nationwide who performed "curative" gastric resections for 453 gastric cancer patients. The most common gastric resection performed was distal in 256 patients, proximal in 118, and total in 79. Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246 (54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7 (1.5%) D3 resections. Staging of the cancer was poorly documented, with no statement made regarding the status of the primary cancer in 6 per cent, liver in 10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater the lymph node clearance, the greater the chance of resecting to a level of negative lymphatics, given that 45 per cent of nodes were involved when 10 or less were removed, whereas only 17 per cent were positive when more than 40 were cleared. The lack of adequate clearance of lymph nodes and poor documentation of tumor stage suggests that a more regimented surgical approach to this uncommon cancer is required.

Documentation↗

Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma.

Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. "Total Therapy" (TT) consisting of noncross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m2 subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM.

Aged↗

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↗