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Biomedical subjects

J Jacobson

Publications and source records attributed to J Jacobson.

At least 73 records · Page 4Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy.

Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety-three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Synergistic effects on ganglionic herpes simplex virus infections by mutations or drugs that inhibit the viral polymerase and thymidine kinase.

Herpes simplex virus encodes proteins, such as DNA polymerase, that are essential for its replication and proteins, such as thymidine kinase, that are not essential for replication in cell culture, but are important for pathogenesis in animal models. However, certain mutations affecting these proteins exert little or no effect on replication or pathogenesis. We tested the effects of combining two such mutations--one that alters DNA polymerase and one that decreases but does not abolish thymidine kinase activity--on replication in cultured cells and on acute and latent infections in mice. The double mutant replicated similarly to the single mutants and wild-type virus both in cell culture and acutely in the mouse eye. However, it was severely impaired for acute replication in trigeminal ganglia and for reactivatable latent infections. This impairment depended upon the polymerase mutation. Similarly, although Ro 31-5140, a thymidine kinase inhibitor, did not potentiate the antiviral effects of phosphonoacetic acid, a polymerase inhibitor, in cell culture, the two drugs in combination substantially inhibited viral reactivation from latency at concentrations that had little or no effect when used singly. These synergistic effects may have implications for viral functions during pathogenesis and for antiviral chemotherapy.

Animals↗
PubMed1994

Sarcomas of the hand and foot: analysis of local control and functional result with combined modality therapy in extremity preservation.

PURPOSE: The records of 28 patients with sarcomas of the hand and foot treated at the National Cancer Institute (NCI) between 1977 and 1992 were reviewed to assess local control and functional results. METHODS AND MATERIALS: Histologic types included 15 cases of the Ewing's sarcoma family of tumors, 7 cases of alveolar rhabdomyosarcoma, and 6 cases of nonrhabdomyosarcoma soft tissue sarcomas. Median age of all patients was 18 years (range 4-61), with a median potential follow-up of 114 months following diagnosis. Surgery varied from incisional biopsies for Ewing's Sarcoma and rhabdomyosarcoma lesions to complete excision when possible for nonrhabdomyosarcoma soft tissue sarcoma lesions. Amputation was not primarily performed, except in two patients who underwent ray resections of hand lesions (patients 13 and 24). Radiotherapy generally consisted of 50 Gy/25 fractions (fx)/5 weeks for Ewing's Sarcoma, 54 Gy/30 fx/6 weeks for rhabdomyosarcoma, and 63 Gy/35 fx/7 weeks for nonrhabdomyosarcoma soft tissue sarcomas. Chemotherapy was administered on various NCI protocols. RESULTS: Actuarial local control for Ewing's Sarcoma was 84% at 5 and 10 years. All but one survivor are capable of hand/foot function for routine activities without orthotic requirements. Five of six patients (83%) who died of metastatic disease had functional distal extremities. Actuarial local control for rhabdomyosarcomas was 100%, with equivalent function. No patient developed a second malignancy in the treatment field. CONCLUSIONS: Although equivalent local control may be achieved in these lesions with either amputation or radiotherapy, a prudent management course would be to defer amputation for management of local recurrences. Many patients with these lesions fail in distant sites only and die without local failure. For these patients and for those who remain long-term survivors, we believe a functional hand and foot provides a better quality of life than a prosthesis.

Adolescent↗
PubMed1994

Early and late cognitive event-related potentials mark stages of HIV-1 infection in the drug-user risk group.

HIV-1 (Human immunodeficiency virus) infection of the brain causes delays in auditory event-related potential (ERP) components. We recorded auditory ERPs from 38 former parenteral drug users (PDUs) at three stages of HIV-1 infection: seronegative; seropositive; stage II; and seropositive, stage IV. There were five response conditions: Go Nogo, Count, Simple Response, Simple Count, and Ignore. P3 peak latencies were significantly delayed and P3 amplitudes were significantly reduced for all seropositives, including asymptomatics, when compared to PDU seronegative controls. In contrast, the P1 and N1 peak latency measures were delayed only for seropositives with acquired immunodeficiency syndrome (AIDS) qualifying illnesses. There was a significant negative correlation between the CD4 count and the latency of P1, N1, and the MMN. Also, increased P1 and N1 amplitudes correlated with indices of disease progression (Choice RT and CD4 counts, respectively). The results extend previous findings by clarifying the pattern of auditory ERP markers of disease progression. Early, as well as late, brain involvement caused by HIV-1 is marked by delays and decreased amplitudes in cognitive components. In addition, late brain involvement is marked by delays and increased amplitudes in specific, automatic, and/or obligatory components.

AIDS Dementia Complex↗
PubMed1994

Perioperative administration of a single dose of conjugated oestrogen to uraemic patients is ineffective in improving haemostasis.

The excessive bleeding that occurs in uraemic patients undergoing surgery is reported to be reversed by at least one schedule of prior oestrogen administration. To assess this possibility a single intravenous injection of 25 mg of the conjugated hormone was given to ten uraemic patients undergoing regular haemodialysis and randomly compared to eight matched patients who received only the diluent. Two hours later there was no reduction in bleeding time, improvement in platelet aggregation, nor an increase in plasma levels of factor VIII (VIII:C), von Willebrand factor (VWF:Ag), or the factor VIII-related ristocetin cofactor state. Furthermore, there was no reduction in intraoperative blood loss, being a median of 558 +/- 154 (range 225-1,260) mL in the test group and 412 +/- 55 (range 270-555) mL in the control and additional median postoperative portovac drainage was 123 +/- 27 (range 0-170) mL and 153 +/- 41 (range 45-240) mL, respectively. These findings differ from the shortening in bleeding time achieved by others with repeated administration of the same agent, and emphasize the importance of dose and duration of oestrogen therapy when used for this indication.

Adolescent↗
PubMed1994

Screening for pregnancy risk-drinking.

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.

Adolescent↗
PubMed1994

Low dose intranasal nafarelin for the treatment of endometriosis.

Twenty-five women with regular menstruation and laparoscopically confirmed endometriosis received 100 mcg nafarelin intranasally twice daily for six months in an open study. American Fertility Society (AFS) laparoscopic scores pre- and post-treatment, symptom severity, hormonal status, bone density and biochemical indices of bone turnover were studied. Five patients were still menstruating at three months and nafarelin was increased to 400 mcg daily. At the end of treatment, the median serum estradiol was 57 pmol/l and all patients were amenorrhoeic. AFS scores for endometriosis improved significantly in 19/23 (82.6%) patients (p = 0.001). Adhesions were not affected. Symptom severity scores were markedly decreased (p < 0.0001) and remained so six months after the end of treatment. Biochemical indices of bone activation were increased but bone loss was insignificant. During treatment, 23/25 patients reported hot flushes. Nafarelin 200 mcg daily significantly reduced signs and symptoms of endometriosis, although five patients needed a dosage increase before menses stopped. The study suggests that lower doses of nafarelin may be efficacious, although symptomatic changes should be treated with caution due to the open and non-comparative nature of the study.

Abdominal Pain↗