Roux-Y Gastric Bypass: an effective anti-reflux procedure

Gastric limiting procedures have made an improvement in the lives of those patients in whom they have been successful. Not only have there been marked improvements in diabetes, hypertension, and arthritis, but there have been a number of other ‘spin-offs’, not the least of which is control of reflux esophagitis by totally eliminating the secretion of the parietal cell mass of the stomach from rising into the esophagus. We compared a group of 100 obese patients with reflux esophagitis who underwent Roux-Y gastric bypass (RYGBP) to a normalsized group of 23 patients on whom we had done Nissen fundoplications in the past. Visick gradings I-II of 100% vs 87%, respectively, may indicate a superiority of RYGBP over the Nissen procedure. Although the groups and time periods are too divergent to draw statistically significant conclusions, one can see that the RYGBP population was apparently better served considering their cure of ‘heartburn’ and other reflux symptoms as well as their achievement of sustained weight loss.     

Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) methods were developed and validated for the evaluation of motexafin lutetium (MLu, lutetium texaphyrin, PCI-0123) pharmacokinetics in human plasma. The LC-MS/MS method was specific for MLu, whereas the ICP-AES method measured total elemental lutetium. Both methods were fast, simple, precise, and accurate. For the LC-MS/MS method, a closely related analogue (PCI-0353) was used as the internal standard (IS). MLu and the IS were extracted from plasma by protein precipitation and injected onto and LC-MS/MS system configured with a C18 column and an electrospray interface. The lower limit of quantitation was 0.05 μg MLu mL⁻¹, with a signal-to-noise ratio of 15∶1. The response was linear from 0.05 to 5.0 μg MLu mL⁻¹. For the ICP-AES method, indium was used as the IS. The sample was digested with nitric acid, diluted, filtered, and then injected onto the ICP-AES system. Two standard curve ranges were validated to meet the expected range of sample concentrations: 0.5 to 50, and 0.1 to 10 μg Lu mL⁻¹. The LC-MS/MS and ICP-AES methods were validated to establish accuracy, precision, analyte stability, and assay robustness. Interday precision and accuracy of quality control samples were ≤6.3% coefficient of variation (CV) and within 2.2% relative error (RE) for the LC-MS/MS method, and ≤8.7% CV and within 4.9% RE for the ICP-AES method. Plasma samples from a subset of patients in a clinical study were analyzed using both methods. For a representative patient, over 90% of the elemental lutetium in plasma could be ascribed to intact MLu at early time points. This percentage decreased to 59% at 48 hours after dosing, suggesting that some degradation and/or metabolism of the drug may have occurred.     

Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.

PURPOSE: This retrospective study was undertaken to assess practice patterns in adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the incidence and predictive factors of reduced relative dose-intensity (RDI). PATIENTS AND METHODS: A nationwide survey of 1,243 community oncology practices was conducted, with data extracted from records of 20,799 ESBC patients treated with adjuvant chemotherapy. Assessments included demographic and clinical characteristics, chemotherapy dose modifications, incidence of febrile neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose-intensity was compared with published reference standard regimens. RESULTS: Dose reductions > or =15% occurred in 36.5% of patients, and there were treatment delays > or =7 days in 24.9% of patients, resulting in 55.5% of patients receiving RDI less than 85%. Nearly two thirds of patients received RDI less than 85% when adjusted for differences in regimen dose-intensity. Multivariate analysis identified several independent predictors for reduced RDI, including increased age; chemotherapy with cyclophosphamide, methotrexate, and fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day schedule; body-surface area greater than 2 m2; and no primary CSF prophylaxis. CSF was often initiated late in the chemotherapy cycle. CONCLUSION: Patients with ESBC are at substantial risk for reduced RDI when treated with adjuvant chemotherapy. Patients at greatest risk include older patients, overweight patients, and those receiving three-drug combinations or 28-day schedules. Predictive models based on such risk factors should enable the selective application of supportive measures in an effort to deliver full dose-intensity chemotherapy.     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

The validity of bioelectrical impedance models in clinical populations.

Bioelectrical impedance analysis (BIA) is the most commonly used body composition technique in published studies. Herein we review the theory and assumptions underlying the various BIA and bioelectrical impedance spectroscopy (BIS) models, because these assumptions may be invalidated in clinical populations. Single-frequency serial BIA and discrete multifrequency BIA may be of limited validity in populations other than healthy, young, euvolemic adults. Both models inaccurately predict total body water (TBW) and extracellular water (ECW) in populations with changes in trunk geometry or fluid compartmentalization, especially at the level of the individual. Single-frequency parallel BIA may predict body composition with greater accuracy than the serial model. Hand-to-hand and leg-to-leg BIA models do not accurately predict percent fat mass. BIS may predict ECW, but not TBW, more accurately than single-frequency BIA. Segmental BIS appears to be sensitive to fluid accumulation in the trunk. In general, bioelectrical impedance technology may be acceptable for determining body composition of groups and for monitoring changes in body composition within individuals over time. Use of the technology to make single measurements in individual patients, however, is not recommended. This has implications in clinical settings, in which measurement of individual patients is important.     

The impact of insulin resistance on the outcome of laparoscopic ovarian electrocautery in infertile women with the polycystic ovary syndrome.

In this study we assessed how insulin resistance affects pregnancy rates in infertile women with the polycystic ovary syndrome (PCOS) treated with laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the study in a consecutive fashion. Following the CIGMA (continuous infusion of glucose with model assessment) test, 28 women were classified as insulin resistant and 36 women as non-insulin resistant. After the ovarian electrocautery patients were observed for 12-18 months. If pregnancy did not ensue, they were referred for one or more cycles of in vitro fertilization (IVF). Following ovarian electrocautery the non-insulin-resistant women more frequently achieved a regular menstrual cycle and ovulation than the insulin-resistant PCOS women. Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a pregnancy versus only five (18%) of women in the insulin-resistant PCOS group. Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non-insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance may be an important marker of a poor outcome of treatment in PCOS infertility. Further studies are needed to evaluate the possible effect of treatment alternatives to alleviate the unfavorable influences of insulin resistance and hyperinsulinemia on ovulation induction in PCOS women.     

Cloning, distribution and functional analysis of the type III sodium channel from human brain

The type III voltage-gated sodium channel was cloned from human brain. The full-length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus, cerebellum, hippocampus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage dependence and kinetics of activation were found to be similar to that of type II. The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials and were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced currents with a prominent persistent component, which were similar to those reported for rat type II [Ma et al. (1997) Neuron, 19, 443-452]. However, unlike type II, this was prominent even in the absence of coexpressed G-proteins, suggesting type III may adopt this gating mode more readily. The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions.     

Botryolides A-E, decarestrictine analogues from a fungicolous Botryotrichum sp. (NRRL 38180)

Four new decarestrictine analogues (botryolides A-D; 1- 4), a biosynthetically related gamma-lactone (botryolide E; 5), and the known compounds decarestrictine D ( 6) and sterigmatocystin have been isolated from cultures of a fungicolous isolate of Botryotrichum sp. (NRRL 38180). The structures of these compounds were determined by analysis of 2D NMR and ESIMS data. The relative configurations of 1- 5 were established on the basis of NMR data and/or X-ray diffraction analysis, while the absolute configuration of 1 was assigned using the modified Mosher method.