Motor control and low back pain in dancers.

Professional dancers suffer a high incidence of injuries, especially to the spine and lower extremities. There is a lack of experimental research addressing low back pain (LBP) in dancers. The aim of this study is to compare lumbopelvic motor control, muscle extensibility and sacroiliac joint pain between dancers with and without a history of LBP. 40 pre-professional dancers (mean age of 20.3 years) underwent a clinical test battery, consisting of an evaluation of lumbopelvic motor control, muscle extensibility, generalized joint hypermobility, and sacroiliac joint pain provocation tests. Also self-reported measurements and standardized questionnaires were used. 41% of the dancers suffered from LBP during at least 2 consecutive days in the previous year. Only one dancer suffered from sacroiliac joint pain. Compared to dancers without a history of LBP, dancers with a history of LBP showed poorer lumbopelvic motor control (p<0.05). No differences in muscle extensibility or joint hypermobility were observed between dancers (p>0.05). Despite their young age, pre-professional dancers suffer from LBP frequently. Sacroiliac joint pain, generalized joint hypermobility or muscle extensibility appears unrelated to LBP in dancers. Motor control is decreased in those with a history of LBP. Further research should examine whether motor control is etiologically involved in LBP in dancers.

Registers for Networked Medical Research in Germany: Situation and prospects.

BACKGROUND: Several disease specific registers are operated by members of the 'TMF - Technology, Methods, and Infrastructure for Networked Medical Research', an umbrella organization of research networks in Germany. OBJECTIVE: To describe the coverage and the current state as well as financial and organizational issues of registers operated by member networks of the TMF, to identify their requirements and needs, and to recommend best practice models. METHODS: A survey with a self-completion questionnaire including all 55 TMF member networks was carried out in winter 2007/2008. Interviews focusing on technological issues were conducted and analyzed in summer 2009 with a convenience sample of 10 registers. RESULTS: From 55 TMF member networks, 11 provided information about 14 registers. Six registers address diseases of the circulatory system with more than 150,000 registered patients. The interviews revealed a typical setting of "research registers". Research registers are an important mean to generate hypotheses for clinical research, to identify eligible patients, and to share data with clinical trials. Concerning technical solutions, we found a remarkable heterogeneity. The analysis of the most efficient registers revealed a structure with five levels as best practice model of register management: executive, operations, IT-management, software, hardware. CONCLUSION: In the last ten years, the TMF member networks established disease specific registers in Germany mainly to support clinical research. The heterogeneity of organizational and technical solutions as well as deficits in register planning motivated the development of respective recommendations. The TMF will continue to assist the registers in quality improvement.

Comparison of 5-fluorouracil alone, 5-fluorouracil with levamisole, and 5-fluorouracil with hepatic irradiation in the treatment of patients with residual, nonmeasurable, intra-abdominal metastasis after undergoing resection for colorectal carcinoma.

BACKGROUND: The authors conducted a randomized Phase III trial of three treatment regimens for patients with residual, nonmeasurable, intra-abdominal metastatic disease after undergoing resection for primary colorectal carcinoma. METHODS: To be eligible for this study, patients had to be both free of other malignancies and capable of starting their therapy within 3-6 weeks after surgery. They were required to have an Eastern Cooperative Oncology Group performance status < 3; to be chemotherapy, radiation, and immunotherapy naïve; to have adequate bone marrow, renal, and hepatic function; and to provide written, informed consent. The patients were divided into two cohorts: patients with no demonstrable hepatic metastasis (Group A) and patients with hepatic metastasis (Group B). RESULTS: The 229 patients in Group A were randomized to receive either 5-fluorouracil (5-FU) (n = 116 patients) or 5-FU with levamisole (n = 113 patients). The median survival (15.4 months and 15.3 months, respectively, for Groups A and B) was virtually identical. The two groups also were similar in terms of time to treatment progression, which was 7.9 months for group that received 5-FU alone 7.7 months for the group that received levamisole with 5-FU. The 168 patients in Group B with hepatic metastasis underwent a three-way randomization: 5-FU alone (n = 60 patients), 5-FU with levamisole (n = 54 patients), and 5-FU with hepatic irradiation (n = 54 patients). The median overall survival for the three treatment arms were similar, with 17.3 months for the group that received 5-FU alone, 16 months for the group that received 5-FU with levamisole, and 14.4 months for the group that received hepatic irradiation in addition to 5-FU: The time to treatment failure was 6.7 months, 6.8 months, and 8.3 months, respectively, for the three groups. The toxicity experienced by patients was as expected with the regimens, and no differences were observed between any of the treatment groups. The primary toxicities were hematologic and gastrointestinal. There was one treatment-related death due to adult respiratory distress syndrome, which occurred on the first day of the fourth cycle of 5-FU and levamisole. Other Grade 4 toxicities included nine patients with Grade 4 leukopenia, one patient with Grade 4 sepsis, and one patient with Grade 4 gastrointestinal toxicity, including blood loss and diarrhea. CONCLUSIONS: This study showed no treatment advantage for any of the combined modalities over 5-FU alone in this group of patients with intra-abdominal, nonmeasurable disease.

Odor input generates approximately 1.5 Hz and approximately 3 Hz spectral peaks in the helix pedal ganglion.

In 1999 we reported that odorants evoke in the Helix pedal ganglion (PG) activity patterns which are largely odorant-specific and related to the nature of odor and its behavioral output. Notably, some activities (for example, approximately 1.5 and approximately 3 Hz), nonspecific to odorants, were consistently evoked in PG. The present contribution goes farther in a deeper survey of the intrinsic and odorant-evoked activities of PG with special weight on the nonspecific fluctuations. We address the following questions. (i) What are the features of the activities? (ii) Are they comparable to the activities found in the motor systems of the other invertebrates? (iii) To what functions can they be related? Three main frequency components represented by power peaks at <1 Hz, 1-2 Hz and 2-8 Hz seem to feature the response activities of PG. (a) The aversive odorants induce odorant-specific patterns represented by peak power frequencies at <1 Hz. (b) The oscillation at approximately 1 Hz, which exists intrinsically in the Helix PG, can be specifically enhanced by appetitive odors. Activities induced in the procerebrum (PC), the visceral ganglion (VG) and PG by appetitive odorants, such as ethanol and apple, peak at 1.3-2 Hz, whereas those induced by aversive ones, such as formic acid and onion at <1 Hz. (c) The 2-8 Hz components always accompany the odorant-evoked activities of the PG either as the second or third strongest component, or in the form of conspicuous, long-lasting approximately 3 Hz oscillations. (d) The nonspecific odor-evoked 1-2 Hz and approximately 3 Hz activities, and the intrinsic approximately 1 Hz activity of the PG seem to be interrelated by a degree of mutual exclusion. We may therefore consider these activities as elementary, slow components that are involved in the processing of signals in this ganglion. It can be inferred from the findings in other invertebrates that the 1-3 Hz spontaneous discharge is strongly connected with motor activity that involves the feedback mechanism of the procerebro-cerebro-buccal or -procerebro-cerebro-pedal circuit. Our approach differs from most others reported so far in the following aspects: (i) use of gross steel electrodes for recording population activities; (ii) lengthy stimulation (10 min); (iii) long observation during and after stimulation; (iv) power spectral presentation of temporal evolution of activity patterns; (v) estimation of peak power frequency by Frequency-Amplitude Plot (FAP) (obtained from signals averaged in the frequency domain; a method based on systems theory).

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282.

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.

Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group.

Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone. Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months). This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed.

PALA versus streptozotocin, doxorubicin, and MeCCNU in the treatment of patients with advanced pancreatic carcinoma.

Seventy-three eligible, chemotherapy-naive, ambulatory patients with advanced pancreatic carcinoma were allocated to one of two treatment regimens: 35 received PALA (1250 mg/m2 daily x 5 every 4 weeks) and 38 were given SAM (streptozotocin 400 mg/m2 i.v. daily x 5, doxorubicin 45 mg/m2 i.v. on day 1 and 22, and methyl CCNU 60 mg/m2 orally on days 1 and 22 every 6 weeks). Doses were modified for myelo-, gi-, or cardiotoxicity. Adequate organ, bone marrow and cardiac function; a measurable lesion; adequate caloric intake; and a life expectancy of 2 months were required for treatment on this trial. One patient on each regimen had a partial response for response rates of 3% (95% confidence intervals, 0.08 to 17%). Median survival on the PALA arm was 5 months and median time to treatment failure was 2.6 months. SAM patients experienced median overall and progression free survivals of 3.4 and 1.9 months, respectively. The severe toxicity observed was almost exclusively myelosuppression on both regimens. One patient receiving SAM had lethal leukopenic sepsis during the first cycle as the only treatment-related death. Neither PALA nor SAM offer any therapeutic utility to patients with advanced pancreatic cancer.

Phase II trials of 5-fluorouracil and leucovorin in patients with metastatic gastric or pancreatic carcinoma.

BACKGROUND: Previous trials in patients with colorectal carcinoma have indicated that enhancement of 5-fluorouracil (5-FU) by leucovorin (LV) can result in an improved response rate and increased survival. METHODS: Phase II trials were performed with patients who had either gastric or papcreatic adenocarcinoma with inetastases. Forty-one gastric carcinoma patients and 31 pancreatic carcinoma patients with measurable disease were treated with 5-FU, 425 mg/m2 intraveneosly (i.v.) on Days 1-5 plus LV, 20 mg/m2 i.v., on Days 1-5, reported at 4 and 8 weeks, and then every 5 weeks thereafter. RESULTS: The patients with metastatic gastric carcinoma had a median survival of 4.8 months. There was a 22% objective response rate, including a 4.9% complete response rate and a 17.1% partial response rate. Among the 31 patients with pancreatic carcinoma, there was a median survival of 5.7 months. No patients in this group showed a response. CONCLUSIONS: The response rate for patients with metastatic gastric adenocarcinoma was modest and this regimen may provide temporary palliation for some patients. However, 5-FU and LV treatment is ineffective against metastatic pancreatic carcinoma.

A phase III evaluation of a somatostatin analogue (octreotide) in the treatment of patients with asymptomatic advanced colon carcinoma. North Central Cancer Treatment Group and the Mayo Clinic.

BACKGROUND: The purpose of this study was to determine by randomized, controlled, double-blind evaluation whether therapy with the somatostatin analogue, octreotide, would delay tumor progression and improve survival of patients with metastatic colorectal carcinomas who were ambulatory with no significant symptoms. METHODS: Two hundred sixty patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and without symptoms related to colon cancer were randomized to receive 150 micrograms of octreotide subcutaneously three times daily or, initially, no treatment. After 91 patients were entered in the double-blind study, saline placebo injections were used for patients in the control arm. RESULTS: The randomization culminated in balanced assignment of patients with respect to disease site(s), presence or absence of measurable or evaluable disease, and interval from diagnosis of metastasis to protocol entry. Steatorrhea and diarrhea, usually mildly severe, resulted more often from treatment than from the placebo. The major end points were time to progression and survival. Curves for both parameters overlapped in the blind and open trial segments. CONCLUSION: Octreotide at a dose of 150 micrograms given three times daily is not effective therapy for patients with advanced asymptomatic colon carcinoma.

Adjuvant therapy for colon cancer.

More tightly defined and controlled studies have found definite benefit associated with adjuvant therapy following surgery for stage III colon cancer. The decision for those with stage II disease is best made on an individual basis.

Development and validation of a sensitive and specific radioimmunoassay for the determination of cicaprost in biological samples.

Cicaprost is a potent, chemically and metabolically stable PGI2-mimetic. Pharmacodynamic effects were observed after oral administration of approximately 10 micrograms in man when plasma levels were in the low pg-range. The present report describes the development of a selective antiserum and a tracer with high specific activity and their use for the RIA determination of Cicaprost in biological samples. Cicaprost-[3H]-methylester with a specific activity of 819 GBq/mmol was used as a tracer. RIA-analyses were carried out with 0.05-0.5 ml plasma adjusted to pH 2 with 1 N HCl and extracted with 2.5 ml diethylether. Separation of antiserum bound and unbound Cicaprost was achieved by the charcoal method. Extraction recovery of Cicaprost was approximately 90% at pH approximately 2. The detection limit of the assay was 10-20 pg/ml plasma. Coefficients of variations were 6, 3 and 9% (within-day, n = 5) and 25, 12 and 10% (day-to-day, n = 11) at 50, 100 and 200 pg/ml. HPLC-chromatograms of plasma extracts did not reveal any peak apart from Cicaprost, demonstrating the specificity of the method. The present RIA for Cicaprost exhibits high specificity and sensitivity and will be used for further bioanalyses in pharmacokinetic study.

Pseudomyxoma peritonei. Long-term patient survival with an aggressive regional approach.

OBJECTIVE: The aims of this study were to analyze the natural history of patients with pseudomyxoma peritonei (PMP), evaluate clinical and pathologic variables as prognostic indicators, and review the authors' experience with different treatments. SUMMARY BACKGROUND DATA: PMP is an unusual form of intra-abdominal neoplasm that presents with large amounts of extracellular mucin. Diffuse peritoneal spread occurs in most patients with PMP, and distant metastasis is infrequent. Debulking surgery, radiation therapy (radioisotope and external beam), and chemotherapy (both intraperitoneal and systemic) have all been advocated for optional patient management, but the variability of patients studied, the small patient numbers, and the prolonged course of this disease make the evaluation of results difficult. METHODS: Fifty-six patients were treated for PMP at the Mayo Clinic between 1957 and 1983. The data were collected retrospectively. Univariate (log-rank test) and multivariate (Cox regression model) analyses were performed for disease recurrence and patient survival. RESULTS: Most patients with PMP had carcinomas of the appendix (52%) or ovary (34%). All gross tumor could be removed only in the 34% of patients with limited disease. Although tumor progression occurred in 76% of patients, the 1-, 5-, and 10-year survival rates were 98%, 53%, and 32%, respectively. Adverse predictors of patient survival included weight loss (p = 0.001), abdominal distention (p = 0.004), use of systemic chemotherapy (p = 0.005), diffuse disease (p = 0.038), and invasion of other organs (p = 0.04). Intraperitoneal chemotherapy (p = 0.009) and radioisotopes (p = 0.0043) both were effective in prolonging the recurrence time of symptomatic PMP. CONCLUSIONS: Although PMP is an indolent disease, aggressive surgical debulking followed by intraperitoneal radioisotopes and/or chemotherapy should be considered because of the diffuse peritoneal involvement.

Prospective phase I evaluation of radiation therapy, 5-fluorouracil, and levamisole in locally advanced gastrointestinal cancer.

PURPOSE: A recent clinical trial in patients with resected node-positive colon cancer demonstrated a clear survival advantage for patients treated with adjuvant 5-fluorouracil and levamisole. This finding led to interest in development of a Phase III trial comparing 5-fluorouracil and levamisole with 5-fluorouracil, levamisole, and radiation therapy in colon cancer patients at high risk for local recurrence. A prospective evaluation of 5-fluorouracil, levamisole, and radiation therapy was undertaken with the goal of establishing a satisfactorily tolerated regimen. METHODS AND MATERIALS: Fifteen patients were studied who had locally advanced or locally recurrent upper abdominal gastrointestinal cancer (11 patients) or large bowel cancer confined to the pelvis (4 patients). The tumor and regional lymph nodes received 45 Gy in 25 fractions. Patients with pelvic tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5 fractions. Systemic therapy consisted of 5-fluorouracil, 450 mg/m2, given intravenously for 3 consecutive days during the first and last weeks of radiation therapy. Levamisole, 50 mg, given orally 3 times daily was used for 3 consecutive days concurrent with initiation of radiation therapy and 5-fluorouracil, at the beginning of the third week of radiation therapy, and concurrent with the final 3-day course of 5-fluorouracil. RESULTS: Therapy was generally well tolerated. In two patients, > or = grade 3 nonhematologic toxicity developed and consisted of transient small bowel obstruction in one and severe nausea and vomiting related to levamisole administration in another. One patient experienced grade 3 hematologic toxicity with a leukocyte count nadir of 1,600 cells/microL. CONCLUSIONS: These results are similar to the toxicity profile reported elsewhere for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation therapy and 5-fluorouracil does not appear to increase toxicity significantly.

Evaluation of external-beam radiation therapy plus 5-fluorouracil (5-FU) versus external-beam radiation therapy plus hycanthone (HYC) in confined, unresectable pancreatic cancer.

From March 1981 to November 1987, 87 patients with histologically confirmed pancreatic adenocarcinoma, unresectable but confined to the pancreatic region, were randomized to two treatments. The standard treatment was 40-50 Gy external-beam radiation therapy (RT) to gross tumor plus potential microscopic tumor with a 5 Gy boost to gross tumor plus a 1.5-2.0 cm margin, using multiple fields and 5-fluorouracil (5-FU) 500 mg/m2/d intravenously by rapid infusion. The 5-FU was given each of the initial 3 days of each of three 20 Gy radiation courses. The experimental treatment used identical radiation fields, but the two Gy daily radiation fractions were administered in a continuous course to a total dose of 50 Gy. Hycanthone was administered 60 mg/m2 intravenously within 2 to 4 hr during each day of the 5-day course of infusions during the first and fifth weeks of radiation therapy. There was no statistically significant difference between treatment arms in survival (p = 0.82) or disease-free survival (p = 0.27). Seven percent of hycanthone-treated patients demonstrated hepatic toxicity which was usually mild in nature. There was, however, one death due to hepatic toxicity.

Phase II trial of VP-16, bleomycin, and cisplatin in patients with advanced nonsquamous cell head and neck neoplasms.

We observed a 45% response rate from the combination of VP-16, bleomycin, and cisplatin among 20 patients with nonsquamous cell head and neck cancer. The regressions were partial and typically occurred within 1 to 2 months of commencing treatment. The median response duration for responding patients was 3 months. Median survival of responders was 8 months, similar to that of all study participants. Gastrointestinal and hematologic sequelae were predictable and manageable. This regimen may provide some transient palliation for selected patients with these neoplasms, but no substantive impact on survival.

Inhibition of type 1 human immunodeficiency virus replication by a tat antagonist to which the virus remains sensitive after prolonged exposure in vitro.

The transactivator of transcription, Tat, of human immunodeficiency virus type 1 (HIV-1) is required for viral replication. Inhibition of Tat function could have the potential to keep integrated provirus in dormancy. In the presence of Tat, Ro 24-7429, an analog of Ro 5-3335, inhibited expression of indicator genes controlled by the HIV-1 long terminal repeat promoter in transient transfection assays and in a constitutive cell line at noncytotoxic concentrations. Reduction of steady-state mRNA of the indicator gene by the compound correlated with reduction of the gene product in the constitutive cell line. Ro 24-7429 has broad activity against several strains of HIV-1 in different cell lines, peripheral blood lymphocytes, and macrophages (IC90 = 1-3 microM). Importantly, Ro 24-7429 inhibited viral replication in both acute and chronic infection in vitro, a characteristic expected of a Tat antagonist and not shared by viral reverse transcriptase inhibitors. Consistent with this, the compound reduced cell-associated viral RNA and proteins and partially restored cell-surface CD4 in chronically infected cells. After 2 years of continued weekly passage of the virus in fresh CEM cells grown in the presence of the compound at 1 or 10 microM, the virus did not develop resistance to the drug. These results indicate that the compound's action might involve a cellular factor.

Multifocal leukoencephalopathy: occurrence during 5-fluorouracil and levamisole therapy and resolution after discontinuation of chemotherapy.

We report the fourth case of cerebral demyelinating disease associated with 5-fluorouracil and levamisole hydrochloride therapy for adenocarcinoma of the colon. The initial manifestations included subacute progressive decline in mental status, ataxia, dysarthria, and diplopia. Magnetic resonance imaging of the head demonstrated multifocal enhanced lesions in the white matter. The patient experienced improvement, without corticosteroid treatment, from 2 weeks to 4 months after cessation of chemotherapy.

Combined doxorubicin and alpha-interferon therapy of advanced hepatocellular carcinoma.

BACKGROUND: Modest activity for doxorubicin has been detected repeatedly for the therapy of advanced hepatocellular carcinoma. Variable activity in this disease also has been documented for alpha-interferon. Preclinical data indicated the possibility that alpha-interferon could enhance or add to the cytotoxic effect of doxorubicin. METHODS: The authors evaluated the use of alpha-interferon at a dose of 12 x 10(6) units/m2/day for 5 days given by intramuscular injection plus doxorubicin 25-40 mg/m2 given intravenously on day 3 (both repeated every 4 weeks) for the treatment of advanced hepatocellular carcinoma. RESULTS: Among 31 eligible patients treated, there was only one instance of objective tumor regression. The median survival for all patients was 10 months. Both hematologic and nonhematologic toxicity were significant but tolerable to the patients. CONCLUSIONS: The 3% response rate indicated that, by the method used, the addition of alpha-interferon to doxorubicin does not improve the clinical effectiveness. This combination cannot be recommended for further study.