Chemotherapy-induced nausea

The rubric complementary medicine covers a variety of approaches that may seem alike only in their being outside conventional care and training. We have asked experienced practitioners to present their own pieces of this jigsaw, realising that these clinical fragments, when seen together, create excitement but also confusion. Of course, this forum is not intended to be a comprehensive review of relevant complementary treatments, and often the individual apporaches to clinical problems will appear totally unrelated, while their apparent effectiveness stretches the biomedical model and conventional research methodology beyond their capacity. With this in mind, we intend that forthcoming articles and reviews will expand on the therapies themselves, and discuss the evidence supporting them.     

Effect of endothelium on beta-VLDL metabolism by cultured smooth muscle cells of differing phenotype

The effect of endothelial cells (EC) on the binding and internalisation of beta-very low density lipoprotein (beta-VLDL) and the subsequent accumulation of lipid was investigated in cultured smooth muscle cells (SMC) of different phenotype. The following combinations were examined: (i) SMC cultured and incubated with 125I-beta-VLDL without EC: "control" cultures; (ii) SMC co-cultured with EC and incubated with 125I-beta-VLDL without EC: "separated" cultures; and (iii) SMC co-cultured with EC and incubated with 125I-beta-VLDL in the presence of EC: "co-incubated" cultures. SMC were in the contractile (CON), reversible synthetic (RS) or irreversible synthetic (IRS) phenotype and EC were either actively proliferating or confluent and quiescent. All three SMC phenotypes showed the greatest capacity to bind and internalise 125I-beta-VLDL with accumulation of lipid when "co-incubated" with confluent EC. SMC "co-incubated" with proliferating EC showed a lower capacity to bind and internalise the lipoprotein and accumulate lipid, while "control" SMC showed the lowest capacity for all phenotypes. IRS SMC bound more 125I-beta-VLDL than either RS or CON state phenotypes. In addition, IRS SMC "co-incubated" with confluent EC showed the greatest degree of binding, and IRS SMC incubated with EC-conditioned medium and EC-conditioned 125I-beta-VLDL showed a significant increase in binding above control (fresh medium and fresh 125I-beta-VLDL). The degree of binding 125I-beta-VLDL to SMC was affected by the functional state of the EC. That is, SMC "co-incubated" with confluent EC bound more lipoprotein than SMC "co-incubated" with the same number of proliferating EC. These results are consistent with observations by others who report preferential lipid accumulation in regions of denuded artery recently recovered by endothelium compared with regions lacking an endothelium. The results also indicate that the EC both modify the beta-VLDL particle and affect the biology of the SMC themselves.     

Magnetic resonance imaging evaluation of muscle usage associated with three exercises for rotator cuff rehabilitation.

PURPOSE: Methods of determining muscle usage for exercises involving rotator cuff muscles are limited. Therefore, this investigation used magnetic resonance imaging (MRI) to evaluate the effect of three different exercises used for rehabilitation of the rotator cuff. METHODS: Five normal volunteer subjects (3 men, 2 women, mean age 31.4 yr) were studied. The exercises were scaption with internal rotation (SIR), military press (MP), and side-lying 45 degrees abduction (SLA). MR imaging was performed immediately before and after exercise using a "fast" spin echo STIR sequence and oblique coronal plane imaging. Changes in signal intensity pre- and post-exercise were measured at comparable section locations for the MR images of the supraspinatus, infraspinatus, teres minor, subscapularis, deltoid, and trapezius. RESULTS: The SLA showed the greatest increase in signal intensity in all the muscles (percent change, P < 0.01) except for the trapezius, which was used more by the MP and SIR. None of the exercises activated the teres minor (percent change, P = not significant). CONCLUSION: These findings have important implications in efficacy of physical rehabilitation of the rotator cuff and avoidance of subacromial impingement exercise motions.     

Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels

The S4 transmembrane segment is the primary voltage sensor in voltage-dependent ion channels. Its movement in response to changes in membrane potential leads to the opening of the activation gate, which is formed by a separate structural component, the S6 segment. Here we show in voltage-, Ca2+-, and Mg2+-dependent, large conductance K+ channels that the S4 segment participates not only in voltage- but also Mg2+-dependent activation. Mutations in S4 and the S4-S5 linker alter voltage-dependent activation and have little or no effect on activation by micromolar Ca2+. However, a subset of these mutations in the C-terminal half of S4 and in the S4-S5 linker either reduce or abolish the Mg2+ sensitivity of channel gating. Cysteine residues substituted into positions R210 and R213, marking the boundary between S4 mutations that alter Mg2+ sensitivity and those that do not, are accessible to a modifying reagent [sodium (2-sulfonatoethyl)methane-thiosulfonate] (MTSES) from the extracellular and intracellular side of the membrane, respectively, at -80 mV. This implies that interactions between S4 and a cytoplasmic domain may be involved in Mg2+-dependent activation. These results indicate that the voltage sensor is critical for Mg2+-dependent activation and the coupling between the voltage sensor and channel gate is a converging point for voltage- and Mg2+-dependent activation pathways.     

Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus

Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor-prognosis subset of patients with esophageal cancer.