Spinal cord stimulation and the relief of chronic pain.

Twenty six patients who had received spinal cord stimulation for chronic pain were evaluated by videotaped structured interviews with staff not directly involved in the patients' care. In addition estimates of pain relief were obtained from clinicians involved in the patients' care and from close relatives and friends. Information about lifestyles and drug usage was also collected and correlated with pain relief. At the time of the interviews half of the patients were receiving 50% or better relief of their pain.     

Clinical MR imaging with a Helmholtz-type surface coil

Limited-field-of-view radio-frequency receiver antennas provide improved near-field sensitivity for magnetic resonance imaging by decreasing the antenna volume. The Helmholtz-type surface coil, consisting of two flat rings, is an organ-encompassing antenna that takes advantage of this principle to yield an improved signal-to-noise ratio (S/N). The coil was tested in a group of 50 patients and 16 healthy volunteers. Images obtained with the Helmholtz coil demonstrated quantitatively superior S/N of 2.2-fold or greater than that of comparison body coil images, as well as qualitatively superior anatomic resolution.     

Molecular characterization of Waldenstrom's macroglobulinemia reveals frequent occurrence of two B-cell clones having distinct IgH VDJ sequences.

PURPOSE: Malignant B lineage cells in Waldenstrom's macroglobulinemia (WM) express a unique clonotypic IgM VDJ. The occurrence of biclonal B cells and their clonal relationships were characterized. EXPERIMENTAL DESIGN: Bone marrow and blood from 20 WM patients were analyzed for clonotypic VDJ sequences, clonal B-cell frequencies, and the complementary determining region 3 profile. RESULTS: Two different clonotypic VDJ sequences were identified in 4 of 20 WM. In two cases, partner clones had different VDJ rearrangements, with one clonotypic signature in bone marrow and a second in blood. For both cases, the bone marrow clone was hypermutated, whereas the blood clone was germ line or minimally mutated. In two other cases, partner clones shared a common VDJ rearrangement but had different patterns of somatic mutations. They lacked intraclonal diversity and were more abundant in bone marrow than in blood. VDJ mutation profiles suggested they arose from a common IgM progenitor. Single-cell analysis in one case indicated the partner clones were reciprocally expressed, following rules of allelic exclusion. CONCLUSIONS: The existence of two B-cell clones having distinct VDJ sequences is common in WM, suggesting that frequent transformation events may occur. In two cases, the partner clones had distinct tissue distributions in either blood or bone marrow, were of different immunoglobulin isotypes, and in one case exhibited differential response to therapy. The contributions of each clone are unknown. Their presence suggests that WM may involve a background of molecular and cellular events leading to emergence of one or more malignant clones.     

A distinctive interaction between memory and chronic daytime somnolence in asymptomatic APOE e4 homozygotes

STUDY OBJECTIVES: To correlate memory measures with a trait measure of chronic daytime somnolence in cognitively normal individuals with different gene doses of the apolipoprotein E (APOE) e4 allele, a common Alzheimer's disease susceptibility gene. DESIGN: Cross-sectional, exploratory study of cognitive abilities in APOE e4 homozygotes (HMZ) (n=42), heterozygotes (HTZ), (n=42) and noncarriers (NC) (n=42) who are matched for age, gender, educational level, and family history of dementia. SETTING: Tertiary care academic medical center. PARTICIPANTS: Cognitively normal residents of Maricopa County, Arizona who are 30-70 years of age, genotyped for APOE, and have no history of a sleep disorder INTERVENTIONS: N/A. MEASUREMENTS: Epworth Sleepiness Scale (ESS) and a battery of neuropsychological tests RESULTS: Age, education, gender, and insomnia complaints did not significantly differ among groups. Despite normal baseline memory scores, memory declined with increasing ESS on all eight memory measures in the HMZ, two of eight in the HTZ, and one of eight in the NC. Differences between HMZ and NC on the slope of memory decline with increasing ESS reached statistical significance on two verbal memory measures, AVLT Long-Term Memory (p=0.048) and Percent Delayed Recall (p=0.035). CONCLUSIONS: Chronic daytime somnolence is associated with a distinctive decline in verbal memory in cognitively normal APOE e4 HMZ, a group at particularly high risk of Alzheimer's disease. Additional studies are needed to confirm these exploratory findings and to determine the effects of acute somnolence on cognition in these genetic subgroups.     

IgG antibodies, chronic bronchitis, and pulmonary function values in farmer's lung patients and matched controls

We measured IgG antibody levels against eight different microbes in farmer's lung (FL) patients an average of 14 years after the first diagnosed episode of FL and in matched controls. The study population consisted of 87 FL patients and 81 control farmers, matched by age, sex, and smoking habits. Clinical studies included the measurement of IgG antibody levels against Absidia corymbifera, Aspergillus umbrosus, A. fumigatus, Humicola grisea, Saccharopolyspora rectivirgula, Penicillium brevicompactum, Rhodotorula glutinis, and Thermoactinomyces vulgaris, in addition to spirometry, pulmonary diffusing capacity (DL(CO)), and the evaluation of chronic bronchitis. Median IgG antibody levels were two or more times higher in FL patients than control farmers against Ab. corymbifera, S. rectivirgula, and T. vulgaris (P<0.001). Against A. fumigatus, H. grisea, and R. glutinis, FL patients also had significantly higher antibody levels. FL patients often had positive antibody titers against several microbes, whereas control farmers usually had a positive titer against one or two microbes. A positive association between IgG antibody levels and chronic bronchitis and DL(CO) was observed in FL patients, but not in control farmers. It is suggested that the high antibody levels noted in FL patients were due not only to high exposure but also to individual sensitivity to environmental microbes.     

9:30-9:45. Preliminary Evaluation of F-18 Fluorocholine (FCH) as a PET Tumor Imaging Agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.     

An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity

Purpose

Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity.

Methods

Data from a clinical study (n?=?24) of patients with breast cancer receiving adjuvant intravenous FE₁₀₀C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC).

Results

Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3?kg. LBM was associated with neutrophil nadir (r?=?0.5, P?=?0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2?kg, P?=?0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC.

Conclusion

To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.     

Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.Subject terms: Combination drug therapy, Cancer therapeutic resistance, Targeted therapies     

The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma

One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4).Presented in part at the Tripartite Meeting, Birmingham, United Kingdom, June 19–21, 1989.