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Biomedical subjects

L Shulman

Publications and source records attributed to L Shulman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Continuous-infusion cisplatin, 5-fluorouracil, and leucovorin for advanced non-small cell lung cancer.

BACKGROUND: Cisplatin, 5-fluorouracil, and leucovorin (PFL) have demonstrated synergistic activity in preclinical models. Continuous infusion of these agents maximizes the potential for synergistic interaction and forms the basis of the PFL regimen. METHODS: Sixty-one patients with advanced (Stages IIIB and IV) non-small cell lung cancer were entered into the study. Thirty-one were treated with cisplatin 25 mg/m2/day on days 1-5, 5-fluorouracil 800 mg/m2/day on days 2-6, and calcium leucovorin 500 mg/m2/day on days 1-6. Because of severe mucositis, the final 30 patients were treated with the same dosage of cisplatin but with the deletion on day 6 of leucovorin and 5-fluorouracil. Cycles were repeated every 28 days. Response was assessed after two cycles. Responding patients received an additional two cycles. Patients with Stage IIIB disease received radiation therapy to the mediastinum and sites of involved disease. RESULTS: PFL had an overall response rate of 41%. Median survival was 8.1 months, and median time to treatment failure was 4.2 months. Importantly, 68% (17 of 25) of responses were maximal after just two cycles of chemotherapy. Notable toxicities included mucositis (43% > or = Grade 3) and myelosuppression. Response, time to failure, or survival did not differ between the two schedules. Mucositis was less severe with 4-day PFL. CONCLUSIONS: PFL as given in this manner is an active regimen for the treatment of patients with advanced non-small cell lung cancer. The rapidity of response makes it a regimen for incorporation into protocols for Stage IIIA disease. A neoadjuvant study using PFL is underway.

Adult↗
PubMed1994

Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression.

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.

Adolescent↗
PubMed1994

Verapamil inhibits B-cell proliferation and tumor necrosis factor release and induces a clinical response in B-cell chronic lymphocytic leukemia.

Four B-CLL patients, treated with verapamil for cardiac problems, showed substantial reduction of lymphadenopathy in one, a 3- and 5-year stabilization of B-CLL in two patients, and a dramatic decrease in lymphocyte count, lymphadenopathy and splenomegaly in one stage IV patient. We therefore studied the effects of verapamil on B-CLL cells in vitro. In 13 samples we observed that verapamil strongly inhibited in vitro proliferation of pokeweed mitogen (PWM) stimulated and unstimulated cells. Using a cytotoxic bioassay, we found that verapamil markedly inhibited the spontaneous and PMW-induced release of tumor necrosis factor (TNF) by B-CLL cells. These findings suggest that verapamil may block B-CLL cell proliferation through inhibition of TNF release and thereby may contribute to the management of B-CLL.

Aged↗
PubMed1993

Identification of feline- and canine-like rotaviruses isolated from humans by restriction fragment length polymorphism assay.

Restriction fragment length polymorphism assay of reverse-transcribed and polymerase chain reaction-amplified rotavirus gene segment 9 was developed to differentiate human serotype 3 rotaviruses from animal serotype 3 rotaviruses. On the basis of similarities or differences in HinfI and DdeI restriction profiles, unusual group A serotype 3 human rotaviruses that belonged to subgroup I were shown to be of feline and canine origin. By this approach, the new human rotavirus isolates 5193, AU-387, AU-720, AU-785 and AU-1115 were shown to resemble certain feline-like human rotaviruses. Similar results were previously obtained by Nakagomi et al. (O. Nakagomi, A. Hoshima, Y. Aboudy, I. Shif, M. Mochizuki, T. Nakagomi, and T. Gotlieb-Stematsky. J. Clin. Microbiol. 28:1198-1203, 1990) by using RNA-RNA cross hybridization with established feline rotaviruses. The restriction fragment length polymorphism assay can provide fast and valuable information on the interspecies transmission of rotaviruses in nature.

Animals↗
PubMed1993

Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer.

PURPOSE: The prognosis and factors that influence prognosis following salvage mastectomy in patients with recurrence in the treated breast after conservative surgery (CS) and radiation therapy (RT) were investigated. MATERIALS AND METHODS: A total of 1,593 patients with stage I or II invasive breast cancer were treated following gross total excision of the tumor at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. One hundred sixty-six of the 1,593 (10%) had subsequent recurrence in the breast. Of these, 123 had salvage mastectomy and constitute the study population. The recurrent tumor was predominantly invasive in 99 patients, noninvasive in 14, and focally invasive in 10. Following mastectomy, chemotherapy or hormonal therapy was administered to 29 patients. The median follow-up time was 39 months after salvage mastectomy. RESULTS: The 5-year actuarial rate of further local or distant relapse for the entire group was 41%. None of the 24 patients with focally invasive or noninvasive tumors had a subsequent relapse. In comparison, the 5-year actuarial rate of further relapse in the 99 patients with a predominantly invasive recurrence was 52% (P = .001). The method of detection of the recurrence, the age of the patient at initial diagnosis, the disease-free interval, and the location of the recurrence in the breast were not found to have a statistically significant association with the risk of further relapse. CONCLUSION: We conclude that the histology of the recurrent tumor is an important prognostic factor for the risk of further relapse. Patients with purely noninvasive or focally invasive tumors have an excellent prognosis following salvage mastectomy. In contrast, patients with predominantly invasive tumors are at substantial risk for further relapse.

Adult↗
PubMed1992

Effect of low-calorie diets on the sympathetic nervous system, body weight, and plasma insulin in overweight hypertension.

When weight reduction was found to decrease blood pressure in the overweight hypertensive patient, it was hailed as the causative factor. A growing number of recent studies indicate that this association may be secondary to a correlation between diet-associated metabolic change and the sympathetic nervous system. A select group such as overweight hypertensive patients may have a genetic predisposition for such a correlation. In overweight hypertensive patients, low-calorie diet and especially very-low-calorie diet, correlate with improved glucose metabolism, a decrease in plasma insulin concentration, and altered norepinephrine concentrations and thus sympathetic nervous system activity. Several of these studies also show a lack of effect of salt intake on blood pressure. Thus, it seems that metabolic changes caused by the decrease in caloric intake are responsible for the decrease in blood pressure. These must be investigated to understand the effect of the different diets on blood pressure. Very low-calorie diets were found very useful in breaking the vicious circle of severe nonresponsive hypertension to medication.

Blood Pressure↗
PubMed1991

Combination of etanidazole with cyclophosphamide and platinum complexes.

In an effort to improve the therapeutic efficacy and selectivity of cyclophosphamide (CTX), cis-diamminedichloroplatinum(II) (CDDP), and carboplatin (Carbo), these antitumor alkylating agents were combined with the 2-nitroimidazole drug etanidazole (ETA). As revealed by tumor-cell survival assay in the FSaIIC murine fibrosarcoma, the addition of ETA (1 g/kg, i.p.) just prior to the i.p. injection of various doses of the alkylating agents resulted in increases in the tumor-cell kill produced by each drug (CTX, 10-fold; CDDP, 20-fold; and Carbo, 5- to 15-fold), whereas toxicity to bone marrow granulocyte-macrophage colony-forming units (CFU-GM) increased only about 0- to 3-fold. When CTX was combined with either CDDP or Carbo, striking increases in tumor-cell killing were observed (20- to 100-fold across the CDDP dose range and 5- to 20-fold across the dose range of Carbo), which were supra-additive for CDDP and additive for Carbo as revealed by isobologram analysis. The addition of ETA to these alkylating-agent combinations produced a further approx. 20-fold increase in tumor-cell kill for both CTX/CDDP and CTX/Carbo. This effect was greatest at the lowest dose of the platinum drug tested and was supra-additive in the case of CDDP and additive for Carbo. Following treatment with ETA/CTX/CDDP, bone marrow CFU-GM toxicity increased only about 5-fold over that of CTX/CDDP alone, but the injection of ETA/CTX/Carbo resulted in a 10- to 20-fold increase in bone marrow toxicity as compared with that obtained using CTX/Carbo alone. Tumor growth-delay studies revealed significant increases in the antitumor effect of the alkylating agents when these were given in combination with ETA. Both the ETA/CTX/CDDP and the ETA/CTX/Carbo combinations produced tumor growth delays of 23 days, which represented approx. 1.6-fold increases over those obtained using the alkylating-agent combinations alone. These results suggest that ETA could significantly improve the therapeutic efficacy of these alkylating agents, whether they are given individually or in combination.

Animals↗
PubMed1991

Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction.

During pregnancy, nucleated fetal erythrocytes enter the maternal circulation and can be isolated efficiently from the maternal cells by multiparameter flow cytometry. Male DNA, implying presence of a male fetus, can be identified in flow-sorted maternal blood by polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific DNA sequences. Among flow-sorted samples, we correctly identified fetal sex in 17/18 (94%) pregnancies of 10-21 weeks gestation. Maternal blood thus provides a potential opportunity for prenatal diagnosis that could preclude the need for invasive procedures in current use.

Base Sequence↗
PubMed1990

Growth hormone therapy.

Growth hormone from human pituitary glands has been available for 30 years. Because of the scarce supply and the danger of transmitting Creutzfeldt-Jakob disease, use of the hormone was discontinued in 1984. Fortunately, synthetic growth hormone produced with recombinant DNA technology became available in 1985 and eliminated the risk of Creutzfeldt-Jakob disease. Growth hormone is approved for use in the treatment of pituitary deficiency syndromes and, when properly administered at an early stage, is capable of inducing normal skeletal and muscular development. It also has been successfully used to augment growth in patients with Turner's syndrome or constitutional growth delay not associated with obvious growth hormone defects. Side effects are generally not serious, but antibodies to growth hormone develop in about 30 percent of patients.

Growth Disorders↗
PubMed1986

Detection of colorectal cancer.

In a series of 47 patients with colorectal cancer, early-stage lesions were detected more frequently on routine screening than on symptomatic screening. Signs and symptoms tended to occur in combination rather than singly. Guaiac positivity was the sole sign in only one patient. Physicians must consider the possibility of colorectal cancer in patients with suggestive signs or symptoms.

Biopsy↗
PubMed1985

Interferon-beta-related DNA on human chromosome 4.

A DNA subclone (pPE-4000) derived from the lambda B4 interferon-beta-related human genomic DNA clone was used as a probe in blot-hybridization experiments of DNA from a panel of human-rodent somatic cell hybrids containing overlapping subsets of human chromosomes. The DNA hybridization experiments showed that the lambda B4 IFN-beta locus is localized to human chromosome 4. A provisional regional assignment to 4q12-qter was also obtained. Thus available hybridization data implicate human chromosomes 2, 4, and 9 in the human IFN-beta system while the available biological data also implicated human chromosome 5.

Animals↗
PubMed1985

Sacral chondromyxoid fibroma.

A 15-year-old girl with a limp and weakness and wasting of the left leg, was found to have a large chondromyxoid fibroma of the sacrum. The lesion presented difficulties in diagnosis because of its unusual site, neurological presentation, large size and extensive extension into the soft tissues of the pelvis and buttock.

Adolescent↗
PubMed1985

Antibody seronegative human T-lymphotropic virus type III (HTLV-III)-infected patients with acquired immunodeficiency syndrome or related disorders.

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Interferon-beta-related DNA is dispersed in the human genome.

Interferon-beta 1 (IFN-beta 1) complementary DNA was used as a hybridization probe to isolate human genomic DNA clones lambda B3 and lambda B4 from a human genomic DNA library. Blot-hybridization procedures and partial nucleotide sequencing revealed that lambda B3 is related to IFN-beta 1 (and more distantly to IFN-alpha 1). Analyses of DNA obtained from a panel of human-rodent somatic cell hybrids that were probed with DNA derived from lambda B3 showed that lambda B3 is on human chromosome 2. Similar experiments indicated that lambda B4 is not on human chromosomes 2, 5, or 9. The finding that DNA related to the IFN-beta 1 gene (and IFN-alpha 1 gene) is dispersed in the human genome raises new questions about the origins of the interferon genes.

Animals↗
PubMed1984

Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21.

We examined the proposed role of human chromosome 21 in determining the cellular sensitivity to human alpha, beta, and gamma interferons (HuIFN-alpha, -beta, and -gamma) and the expression of the receptors for the HuIFNs with the use of mouse-human hybrid cells containing human chromosome 21. Hybrid cells (WA17) containing three copies of human chromosome 21 showed specific displaceable binding of 125I-labeled HuIFN-alpha 2 (125I-HuIFN-alpha 2), which was not observed with mouse parent (A9) cells. Crosslinking of 125I-HuIFN-alpha 2 bound to WA17 cells with disuccinimidyl suberate yielded a complex of Mr approximately equal to 150,000 similar to the 125I-HuIFN-alpha 2-receptor complex obtained with human cells as described earlier. Such a complex was not obtained with mouse parent (A9) cells or with hybrid cells containing certain other human chromosomes but not chromosome 21. Mice inoculated with mouse-human hybrid cells containing human chromosome 21 produce antibodies that block the antiviral action of HuIFN-alpha and -beta on human cells. Such antibodies could immunoprecipitate the 125I-HuIFN-alpha 2-receptor complex obtained from human cells but not free 125I-HuIFN-alpha 2, indicating that these antibodies were directed against the receptor. WA17 hybrid cells were highly sensitive to the antiviral action of HuIFN-alpha 2, -alpha (Le) and -beta but were completely insensitive to HuIFN-gamma. Furthermore, 125I-HuIFN-gamma showed specific binding to human WISH cells but not to WA17 hybrid cells or A9 mouse cells. The results indicate that the receptors for HuIFN-alpha and -beta but not for HuIFN-gamma are specified by human chromosome 21. Hybrid cells containing one, two, or three copies of human chromosome 21 were found to be increasingly sensitive to HuIFN-alpha 2, indicating that a chromosome 21-specified component (possibly the HuIFN-alpha receptor) may be a limiting factor in the cellular sensitivity to HuIFN-alpha.

Animals↗