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N J Meropol

Publications and source records attributed to N J Meropol.

62 records · Page 4Linked to original sources
PubMed1992

The current status of toxicity protectants in cancer therapy.

Current therapies for the treatment of malignancies are associated with significant toxicity, as chemotherapy and radiation therapy do not discriminate between normal and malignant cells. One approach to ameliorating the toxicity associated with therapy is through the use of chemoprotective agents. This article reviews a variety of agents that have been evaluated as possible protectants, including WR-2721 and the colony-stimulating factors. It is hoped that the understanding of how to optimally use chemoprotective agents will lead to more tolerable treatments for patients, and possibly allow for dose-escalation, which may contribute to improvement in patient survival.

Amifostine↗
PubMed1992

High-dose chemotherapy with autologous stem cell support for breast cancer.

Breast cancer is a major public health issue, expected to affect one out of nine women over a lifetime. High-dose chemotherapy with autologous stem cell support is a current approach to the management of metastatic breast cancer and high-risk primary breast cancer. This review considers the effectiveness of this modality in the treatment of breast cancer in an effort to define its role in overall patient management. Current research directions, including technical advances aimed at reducing toxicity, are discussed. Finally, controversies regarding the role of third-party payers in the investigational process are considered.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A neutralizing monoclonal antibody binds to an epitope near the amino terminus of murine granulocyte-macrophage colony-stimulating factor.

A rat anti-murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) monoclonal antibody, A2, that neutralizes bioactivity in vitro was isolated. The binding epitope recognized by this antibody was identified using human-murine hybrid GM-CSF proteins. A2 was unable to immunoprecipitate a hybrid (hm7) protein containing the human GM-CSF sequence for the first 11 amino terminal amino acids, and the mGM-CSF sequence for amino acids 12-124. In contrast, A2 did recognize a hybrid which substitutes human GM-CSF amino acids 23-36 in the murine sequence. These data suggest that this neutralizing antibody recognizes an epitope at the amino terminus of mGM-CSF. Because hm7 did maintain in vitro bioactivity, it is probable that the epitope recognized by the neutralizing antibody is not itself part of the receptor-binding domain of mGM-CSF; rather, it is likely that neutralization occurs as a result of antibody binding near the receptor-binding site, with steric inhibition of mGM-CSF binding to its receptor. Interestingly, monoclonal antibody A2 does not recognize mGM-CSF glycosylation species corresponding to predicted maximal O-glycosylation variants. The presence of O-glycosylation sites within the antibody-binding epitope was confirmed using site-directed mutagenesis. Potential O-glycosylation sites in native mGM-CSF were removed by introducing conservative amino acid substitutions, and expected molecular weight reductions were obtained. These findings are consistent with previous reports that suggest the importance of the integrity of residues near the amino terminus to GM-CSF bioactivity.

Amino Acid Sequence↗
PubMed1989

Tendency to serious sequelae of infection with the human immunodeficiency virus in sibships with hemophilia.

Cofactors for the clinical expression of infection due to the human immunodeficiency virus (HIV) are not well understood. We asked if there was a familial tendency to the development of complications of HIV infection. We examined 35 hemophilic sibships in which at least two brothers with classic hemophilia (factor VIII deficiency) were infected with HIV. Twenty-four (34%) of the 70 patients had serious sequelae of infection, and 46 (66%) were asymptomatic or had only lymph node enlargement. Using Fisher's exact test, we found the concordance among siblings for serious sequelae of HIV infection was greater than would be expected by chance. When analysis was restricted to include only siblings known to be infected for more than two years, this concordance was still present. In the study population, birth order and mean yearly usage of factor VIII concentrate were unrelated to the outcome of HIV infection. The data indicate a familial tendency to serious complications of HIV infection. The factor(s) responsible for this familial tendency are currently under investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1981

Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase-stable cephalosporin.

The in vitro activity of ceftriaxone (Ro 13-9904), a parenteral cephalosporin, was compared with that of other beta-lactam antibiotics. the compound was less active against Staphylococcus aureus and Staphylococcus epidermidis than was cephalothin or cefamandole, but it was comparable to cefoxitin, cefotaxime, and moxalactam in inhibiting most isolates of S. aureus at 3.1 microgram/ml. Ro 13-9904 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at concentrations below 0.25 microgram/ml, but Streptococcus faecalis required concentrations above 25 microgram/ml. Neisseria gonorrhoeae and Haemophilus influenzae were inhibited at concentrations similar to those of cefotaxime, less than 0.1 microgram/ml. Ro 13-9904 was as active as cefotaxime and moxalactam against most Enterobacteriaceae and was the most active agent tested against Proteus, inhibiting all strains tested at 0.006 microgram/ml. Ro 13-9904 was slightly less active than moxalactam or cefoxitin against Bacteroides fragilis, requiring more than 100 microgram/ml to inhibit 90% of isolates, and it was less active than cefoperazone against Pseudomonas aeruginosa. Presence of serum, alteration of pH, and use of various media did not change the inhibitory levels. Bactericidal concentrations were similar to inhibitory levels. Ro 13-9904 was stable to most plasmid-mediated beta-lactamases, but was hydrolyzed by some Enterobacter, Proteus, and Bacteroides beta-lactamases of chromosomal origin.

Bacteria↗
PubMedDate not supplied

Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas.

We examined the effect of preoperative chemoradiotherapy on the ability to obtain pathologically negative resection margins in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between 1987 and 2000, 100 patients underwent Whipple resection with curative intent for primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six margins (proximal and distal superior mesenteric artery, proximal and distal superior mesenteric vein, pancreas, retroperitoneum, common bile duct, and hepatic artery) was undertaken by either frozen section (pancreas and common duct) or permanent section. A margin was considered positive if tumor was present less than 1 mm from the inked specimen. Margins noted to be positive on frozen section were resected whenever possible. Of the 100 patients treated, 47 (47%) underwent postoperative radiation and chemotherapy (group I) and 53 (53%) received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32 patients) or gemcitabine (21 patients). Patient demographics and operative parameters were similar in the two groups, with the exception of preoperative tumor size (CT scan), which was greater in group II (P < 0.001), and number of previous operations, which was greater in group II (P < 0.0001). Statistical analysis of the number of negative surgical margins clear of tumor was performed using Fisher's exact test. All patients (100%) had six margins assessed for microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%) of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47 patients without preoperative therapy had more than one margin with disease extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group receiving preoperative therapy (P = 0.013). Survival analysis reveals a significant increase in survival in margin-negative patients (P = 0.02). Similarly, a strong trend toward improved disease-free and overall survival is seen in patients with a single positive margin vs. multiple margins. Overall, we find a negative impact on survival with an increasing number of positive margins (P = 0.025, hazard ratio 1.3). When stratified for individual margin status, survival was decreased in patients with positive superior mesenteric artery (P = 0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a significant increase in disease-free or overall survival for patients receiving preoperative therapy (P = 0.07).

Adenocarcinoma↗
PubMedDate not supplied

Treatment choices by seriously ill patients: the Health Stock Risk Adjustment model.

Anecdotal evidence suggests that patients who have life-threatening conditions often choose to undergo high-cost, high-risk treatments for them. This kind of risk-seeking behavior seems irrational because most patients are risk-averse. The Health Stock Risk Adjustment (HSRA) model seeks to explain this phenomenon. The model is based on the concept of relative health stock--the ratio of patients' expected quality-adjusted life years (QALYs) after a diagnosis to their expected QALYs before the diagnosis. The model predicts risk-averse patients will behave in a risk-seeking manner as their relative health stocks deteriorate. The HSRA model can help physicians better understand why some seriously ill patients seek high-risk treatments while others elect to forgo treatment. State legislatures and insurers are attempting to appropriately design insurance benefits for patients with life-threatening conditions. The HSRA model can help predict which patients will most likely take advantage of these benefits.

Aged↗