bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Trypanosoma evansi Infection in Equines and Camels in the Punjab Region, Pakistan
Authors: HASAN MURTAZ UL , MUHAMMAD GHULAM , GUTIERREZ CARLOS , IQBAL ZAFAR , SHAKOOR ABDUL , JABBAR ABDUL
Published: November 2006

Abstract:  A cross‐sectional study has been carried out in order to determine the prevalence of Trypanosoma evansi infection in susceptible hosts in the Punjab region (Pakistan). A total of 170 equines and 150 dromedary camels were examined. Five (3.3%) and 6 (4%) camels were positive at parasitological and serological examination, respectively. None of the equines tested positive at any method. These results seem to indicate that T. evansi infection has a relatively low prevalence in the Punjab region. However, efforts must be done in order to establish control measures in affected herds and avoid dissemination of the disease.
Clinical, Hematological, and Biochemical Findings in an Outbreak of Abortion and Neonatal Mortality Associated with Trypanosoma evansi Infection in Dromedary Camels
Authors: GUTIERREZ CARLOS , CORBERA JUAN A. , JUSTE MARIA C. , DORESTE FRANCISCO , MORALES INMACULADA
Published: November 2006

Abstract:  This article presents the clinical and laboratorial findings in an outbreak of abortions and high neonatal mortality attributable to Trypanosoma evansi infection in camels. A total of 16 females were diagnosed, 2 of which showed moderate signs of chronic form, particularly hyporexia and intolerance to exercise. The main laboratorial findings were regenerative anemia (hemolytic anemia), lymphocytic and monocytic leukocytosis, hyperproteinemia, hyperglobulinemia, hypoglycemia, serum urea increased, and serum iron decreased. The most characteristic finding in the examined females would be the uremia, probably due to the higher protein metabolism.
Cysticercosis of Slaughter Cattle in Southeastern Nigeria
Authors: OPARA MAXWELL N. , UKPONG UKEME MICHAEL , OKOLI IFEANYI CHARLES , ANOSIKE JUDE CHUKS
Published: November 2006

Abstract:  The incidence of cysticercosis due to Taenia saginata in both local and exotic breeds of cattle slaughtered for meat in southeastern Nigeria between November 1999 and April 2002 is reported. The examination of various organs of 25,800 cattle in 10 major abattoirs of this region showed that 6750 (26.2%) were infected with Cysticercus (C.) bovis. The prevalence rates varied from one abattoir to another while the rates of cysticercosis in local and exotic breeds varied significantly (P > 0.05). Sixty percent of all the infected animals had cysts. The tongue, cardiac, and masseter muscles were the main predilection sites of the cysts. Out of 11,720 male cattle, examined, 3215 (27.4%) had cysts of C. bovis while 160 (13.6%) of the 1180 female animals investigated were infected. There was an inverse relationship between the ages of the animals and prevalence of infection with C. bovis (r=−0.8743, P < 0.05). Monthly occurrence of the cysts in the animals revealed an upsurge of infected animals during the dry season. The epidemiology and epizootiology of Taenia saginata and C. bovis in relation to the veterinary service agencies and public health planners in southeastern Nigeria are highlighted.
Use of Bacillus thuringiensis Toxin as an Alternative Method of Control against Haemonchus contortus
Authors: LÓPEZ MARIA E. , FLORES JAIME , MENDOZA PEDRO , VÁZQUEZ VICTOR , LIÉBANO ENRIQUE , BRAVO ALEJANDRA , HERRERA DAVID , GODÍNES ELENA , VARGAS PATRICIA , ZAMUDIO FABIAN
Published: November 2006

Abstract:  The biocide activity of Bacillus thuringiensis (B. thuringiensis) IB‐16 strain was evaluated against the blood‐feeding nematode Haemonchus contortus (H. contortus) in vitro and in vivo assays. Twenty experimental jirds (Meriones unguiculatus) and 32 sheep were infected with H. contortus by oral route. Fourteen days post infection 10 jirds were treated with 0.2 mg per mL of IB‐16 soluble toxin by intraperitoneal (i.p.) route and 8 sheep were treated with 0.5 mg of toxin per kg of body weight by intramuscular route 35 days after H. contortus infection. Same number of treated jirds and sheep were used as control. Fecal and blood samples were analyzed from experimental sheep to estimate the number of parasitic eggs, percentage of eosinophils, packed cell volume (PCV), and IgG title. All experimental jirds and 16 sheep (8 treated and 8 controls) were sacrificed at days 5, 7, and 30 after B. thuringiensis treatment. The percentage of nematode reduction was estimated from L4 and H. contortus adults. The percentage of protection was 80.0 to jirds and 73.8 and 53.3 to sheep, sacrificed at days 7 and 30, respectively. Moreover, nonsignificant difference (P≥ 0.05) was detected from parasitic eggs, eosinophils, and PCV parameters. Significance level of IgG was observed only before H. contortus treatment with B. thuringiensis soluble toxin (P≤ 0.05) but nonsignificant difference was observed after treatment. These results showed that B. thuringiensis activity was similar to those observed by anthelmintic treatment and it could be used as an alternative biological method.
New Findings on Anaplasmosis Caused by Infection with Anaplasma phagocytophilum
Authors: LILLINI EUGENIO , MACRÌ GLADIA , PROIETTI GABRIELLA , SCARPULLA MANUELA
Published: November 2006

Abstract: 
Ixodes ricinus (I. ricinus) is one of the vectors of Anaplasma phagocytophilum (A. phagocytophilum) in Europe, in which rates of infection range from 1.9% to 34%. In 1998, human granulocytic ehrlichiosis‐like (HGE‐like) Ehrlichia DNA was detected in Italy, by PCR technique in one I. ricinus nymph out of 55 ticks that were examined. In 1996, 6.3% of 310 human sera in high‐risk subjects from Italy were found positive for antibodies to Ehrlichia phagocytophila (E. phagocytophila). In the same year, the authors reported the first case of equine granulocytic ehrlichiosis. In 1997, only 2 out of 563 equine blood samples examined were found positive for antibodies to E. phagocytophila in the Latium region. In 1998, serological positivity was not observed in 14 symptomatic race horses. In 2002, a symptomatic horse living in Rome was found positive for Ehrlichia equi (E. equi) antibodies, as confirmed by PCR. E. equi was also demonstrated in horses by detection of specific antibodies from two asymptomatic ponies. We tested 128 sera from sheep in different flocks, and antibodies to E. phagocytophila were detected in 17 sera (13.3%) of these sheep. From 2000 to 2004, 147 dog sera were tested for antibodies against A. phagocytophilum, and 7 of these sera were positive (4.8%). These data confirm the presence of the infection in human, domestic animals, and pets in Italy. Studies are under way to correlate the distributions of the disease and tick vector, I. ricinus.
Evaluation of Cattle Inoculated with Babesia bovis Clones Adhesive In Vitro to Bovine Brain Endothelial Cells
Authors: CANTO GERMINAL J. , FIGUEROA JULIO V. , RAMOS JUAN A. , ROJAS EDMUNDO E. , GARCIA‐TAPIA DAVID , ANTONIO ALVAREZ J. , ALLRED DAVID R. , CARSON CHARLES A.
Published: November 2006

Abstract:  A comparative assessment of the virulence of Babesia bovis clones that adhere or not to bovine brain endothelial cells was done using two clones of B. bovis: (1) a clone phenotypically characterized as virulent (2F8) and (2) a clone of reduced virulence (RAD). Of these subpopulations, we selected those that had adhesive characteristics (a) or nonadhesive characteristics (na) in cultured endothelial cells. Twenty Holstein cattle, 12 months of age or older, were used in this study, and these cattle were randomly assigned to five groups of four animals each. The clones and their respective subpopulations were inoculated via intramuscular injection at a 0.5 × 107 infected erythrocyte dosage. Group A was inoculated with aRAD, group B with naRAD, group C with a2F8, group D with na2F8, and group E remained as a control. All inoculated animals showed a decrease in the packed cell volume (PCV), with group D showing the largest decrease (39.53%) and longest time (7 days) with rectal temperature above 39.5°C. Babesia was observed in stained blood smears from only six cattle. While the four parasite subpopulations were pathogenic, significant differences were not noted among them, despite that the subpopulations considered to be virulent caused the greatest reduction in PCV per individual.
Bovine Babesiosis Live Vaccine Production
Authors: ROJAS CARMEN , FIGUEROA JULIO V. , ALVARADO ARCELIA , MEJIA PEDRO , MOSQUEDA JUAN J. , FALCON ALFONSO , VEGA CARLOS A. , ALVAREZ ANTONIO
Published: November 2006

Abstract:  Gamma irradiation on bovine serum and red blood cells (RBC) allows proliferation and growth of in vitro‐cultured Babesia sp., and has potential application to inactivate contaminating viruses and bacteria from the substrate. Gamma irradiation with 25 kGy in a source of 60Co was able to inactivate infectious bovine rinotracheitis (IBR) and bovine viral diarrhea (BVD) viruses in artificially contaminated serum; besides, bacteria were also eliminated. In vitro culture of Babesia bovis (B. bovis) in modified substrate, by adding irradiated serum with 60Co at 25 kGy was propagated from 24‐well culture plates to 225 cm2 tissue culture flasks, and percentages of parasitized erythrocytes (PPE) from 2.4% to 8.8% were obtained. Infected RBC adapted to Irrad S were transferred to the irradiated substrate in vitro culture system, by using serum irradiated at 25 kGy and RBC from 10 to 70 Gy. The PPE ranged from 3.1 to 11. Culture of Babesia bigemina (B. bigemina) was established with Irrad S (25 kGy); its propagation was achieved in tissue culture flasks reaching PPE from 0.5 to 4.3 with no statistical difference (P > 0.05) when compared to the nonirradiated control culture (1.2–4.8). B. bigemina‐infected RBCs were transferred to the modified culture system by adding irradiated serum and RBC (25 kGy and 70 Gy, respectively). PPE obtained in culture flasks were from 0.8 to 4.2. The results indicate that gamma irradiation is a suitable method to inactivate potential viral contamination and eliminate bacteria from bovine serum, to produce a live attenuated vaccine through the in vitro culture.
Emerging Tick‐Borne Disease in African Vipers Caused by a Cowdria‐Like Organism
Authors: KIEL JOHNATHAN L. , ALARCON RODOLFO M. , PARKER JILL E. , VIVEKANANDA JEEVA , GONZALEZ YVETTE B. , STRIBLING LUCILLE J.V. , ANDREWS CARRIE J.
Published: November 2006

Abstract:  Heartwater is a tick‐borne infectious disease caused by the rickettsial organism Cowdria ruminantium, currently Ehrlichia ruminantium. It poses an imminent threat to the Western Hemisphere, where it could cause mortality in cattle and other ruminant livestock in excess of 70%. It has been reported in the Caribbean; and its vector, Amblyomma sparsum, has been found on imported African spurred tortoises (Geochelone sulcata) and leopard tortoises (Geochelone pardalis) in southern Florida in the United States, leading to an importation ban on these reptiles. Symptoms have not been previously reported in reptiles. Here, we report peracute and acute deaths in African vipers imported from Africa through Florida. Signs included vomiting mucoid fluid, diarrhea, emaciation, convulsions, and death. Postmortem showed few gross lesions. The most consistent peracute and acute lesions were the pulmonary lesions and pericarditis with considerable bloody fluid in the pericardial sac (hydropericardium). These lesions strongly resembled the lesions of heartwater and a coccobacillus of less than 1‐micron diameter was isolated in viper cell culture. The outbreak was brought to a halt by tick control and treatment of all exposed snakes with tetracycline. This isolation, tetracycline sensitivity, clinical signs, preliminary results with polymerase chain reaction of pCS20 ORF, and the viper preference of the disease may indicate a Cowdria‐related attenuated species that has adapted to infect reptiles or an emerging new form of this group of microbes.
Investigation of MAP Kinase Activation in Theileria‐Infected Cell Lines
Authors: SEITZER ULRIKE , SCHNITTGER LEONHARD , BOGUSLAWSKI KATI , AHMED JABBAR S.
Published: November 2006

Abstract:  A study on different Theileria annulata and Theileria parva infected cell lines was performed in order to evaluate the general relevance of the MAP‐kinase activation status for Theileria‐ mediated transformation.
Influence of Different Diets on Growth Performance, Meat Quality, and Disease Resistance in Pig Crossbreeds (PIE × MC‐local) and PIE (LW × MC‐ local)
Authors: LINH NGUYEN QUANG , THI BE NGUYEN , DAO DINH THI
Published: November 2006

Abstract:  The present study evaluated the effect of different dietary formulations on the growth rate in pigs and their resistance to infection with hog cholera. Results indicate that growth rates can be enhanced by certain formulations and that there is a correlation between this increased growth rate and increased resistance to infection with hog cholera.
Phase II Study of Cisplatin Plus Epirubicin Salvage Chemotherapy in Refractory Germ Cell Tumors
Authors: Bedano Pablo M. , Brames Mary J. , Williams Stephen D. , Juliar Beth E. , Einhorn Lawrence H.
Published: November 2006

Purpose

Initial cisplatin (CIS) combination chemotherapy will cure 70% of patients with disseminated testicular cancer. This phase II clinical trial evaluated the combination of CIS plus epirubicin (CIS-EPI) in patients with metastatic germ cell tumors (GCT) not amenable to cure with standard salvage therapy.

Patients and Methods

Between March 2001 and August 2005, 30 patients with GCT, who had received at least one previous CIS-based regimen, were enrolled. All patients were males, with median age 36 (range, 24 to 45 years). Twenty-one patients (70%) had experienced late relapses (> 2 years). Patients received EPI 90 mg/m2 on day 1 and CIS 20 mg/m2 on days 1 to 5 every 3 weeks for maximum of four cycles.

Results

Nineteen (63%) of 30 patients received all four cycles. Toxicity was primarily hematologic: grade 3/4 neutropenia, four patients (one neutropenic fever); two patients had grade 3 thrombocytopenia, and five patients had grade 3/4 anemia. Nonhematologic toxicity was grade 3 acute renal failure in two patients; grade 3 electrolyte wasting in two patients; grade 3 nausea/vomiting in eight patients; grade 3 elevation of aminotransferases in one patient; and grade 3 diarrhea in one patient. There were no occurrences of severe mucositis, cardiotoxicity, or treatment-related deaths. Nine patients achieved a complete remission; seven of these patients remain without evidence of disease at 25+, 27+, 29+, 44+, 45+, 46+, and 48+ months. One patient remains alive with stable pulmonary nodules at 28+ months.

Conclusion

CIS-EPI is an active regimen in metastatic GCT, with an acceptable toxicity profile. This regimen offers potential for long-term disease-free survival in this population.
Immunohistochemical Patterns of Reactive Microenvironment Are Associated With Clinicobiologic Behavior in Follicular Lymphoma Patients
Authors: Álvaro Tomás , Lejeune Marylène , Salvadó Maria-Teresa , Lopez Carlos , Jaén Joaquín , Bosch Ramón , Pons Lluis E.
Published: November 2006

Purpose

Recent molecular data have suggested that non-neoplastic cells are powerful modulators that may confer a selective advantage or disadvantage on the outcome of follicular lymphoma (FL) patients.

Patients and Methods

The prevalence of the principal inflammatory and immune-infiltrated cells was measured immunohistochemically in the tissue of 211 FL patients, and associations were sought with their traditional clinicobiologic characteristics.

Results

Our results confirmed the presence of a large number of T lymphocytes (CD4+and CD8+) and CD57+cells and, at a moderate level, the presence of TIA-1+cytotoxic cells, CD68+macrophages, CD123+plasmacytoid cells, and FOXP3+regulatory T cells among the pool of non-neoplastic cells. In addition to the conventional clinical variables, univariate analysis identified a low level of infiltrated CD8+T lymphocytes as a significantly negative prognostic factor of overall survival. The following significant differences in the abundance of cells of specific and nonspecific immunity were observed in relation to the clinicobiologic features of FL: (1) a reactive microenvironment mainly made up of T lymphocytes and macrophages was significantly associated with a favorable clinical behavior of FL patients; and (2) a reactive microenvironment infiltrated predominantly by CD57+T cells was associated with a significantly higher frequency of adverse clinicobiologic manifestations such as “B” symptoms and bone marrow involvement.

Conclusion

Our results demonstrate the existence of two specific patterns in the reactive microenvironment of FL, an immunosurveillance pattern (T lymphocytes and macrophages) and an immune-escape pattern (CD57+T cells), that were directly associated with the clinicobiologic features of these patients.
Phase III Trial Comparing Doxorubicin Plus Cyclophosphamide With Docetaxel Plus Cyclophosphamide As Adjuvant Therapy for Operable Breast Cancer
Authors: Jones Stephen E. , Savin Michael A. , Holmes Frankie Ann , O'Shaughnessy Joyce A. , Blum Joanne L. , Vukelja Svetislava , McIntyre Kristi J. , Pippen John E. , Bordelon James H. , Kirby Robert , Sandbach John , Hyman William J. , Khandelwal Pankaj , Negron Angel G. , Richards Donald A. , Anthony Stephen P. , Mennel Robert G. , Boehm Kristi A. , Meyer Walter G. , Asmar Lina
Published: November 2006

Purpose

The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS).

Patients and Methods

Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor–positive disease, were administered after completion of chemotherapy.

Results

Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure.

Conclusion

At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.
Docetaxel, Estramustine, and 15-Month Androgen Deprivation for Men With Prostate-Specific Antigen Progression After Definitive Local Therapy for Prostate Cancer
Authors: Taplin Mary-Ellen , Xie Wanling , Bubley Glenn J. , Ernstoff Marc S. , Walsh William , Morganstern Daniel E. , Regan Meredith M.
Published: November 2006

Purpose

Androgen-deprivation therapy (ADT) is effective for relapsed prostate cancer, but is rarely curative. The purpose of this trial was to determine the feasibility, toxicity, and prostate-specific antigen (PSA) response of chemotherapy and limited ADT for men with PSA relapse.

Patients and Methods

Eligible men had an increasing PSA and no metastases after prostatectomy and/or radiation for localized disease. Treatment consisted of four cycles of docetaxel (70 mg/m2) every 21 days and estramustine 280 mg tid on days 1 through 5. After chemotherapy, goserelin acetate and bicalutamide were prescribed for 15 months.

Results

Sixty-two patients were enrolled. A complete PSA response (CR) was defined as PSA at or below the assay-specific lower limit. The proportion of patients with CR after chemotherapy, after ADT, and at 1 year after completion of ADT was 53%, 63%, and 36%, respectively. Testosterone was more than 100 ng/dL (median, 250 ng/dL) 1 year after completion of ADT in 97% of patients. Patients with a PSA less than 3.0 ng/mL at enrollment had a significantly longer time to progression (TTP; P = .0004). Of 56 patients who were observed at least 1 year after completion of ADT, 23 (41%) have not experienced progression as of their last follow-up. The median TTP is 34 months from treatment initiation (maximum, 74 months free from progression).

Conclusion

Chemotherapy plus ADT was feasible for early prostate cancer relapse. Forty-one percent of men who are at least 1 year after completion of ADT with recovered testosterone have not experienced progression. This approach is being tested in a randomized trial with investigation of predictors of response.
Plasma Epstein-Barr Viral Deoxyribonucleic Acid Quantitation Complements Tumor-Node-Metastasis Staging Prognostication in Nasopharyngeal Carcinoma
Authors: Leung Sing-fai , Zee Benny , Ma Brigette B. , Hui Edwin P. , Mo Frankie , Lai Maria , Chan K.C. Allen , Chan Lisa Y.S. , Kwan Wing-hong , Lo Y.M. Dennis , Chan Anthony T.C.
Published: November 2006

Purpose

To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC).

Patients and Methods

Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared.

Results

Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease.

Conclusion

Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.
Significance of Necrosis in Grading of Oligodendroglial Neoplasms: A Clinicopathologic and Genetic Study of Newly Diagnosed High-Grade Gliomas
Authors: Miller C. Ryan , Dunham Christopher P. , Scheithauer Bernd W. , Perry Arie
Published: November 2006

Purpose

High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial.

Patients and Methods

Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH).

Results

Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P ≤ .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH.

Conclusion

Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.
Efficacy of Complementary and Alternative Medicine Therapies in Relieving Cancer Pain: A Systematic Review
Authors: Bardia Aditya , Barton Debra L. , Prokop Larry J. , Bauer Brent A. , Moynihan Timothy J.
Published: November 2006

Purpose

Despite widespread popular use of complementary and alternative medicine (CAM) therapies, a rigorous evidence base about their efficacy for cancer-related pain is lacking. This is a systematic review of randomized controlled trials (RCTs) evaluating CAM therapies for cancer-related pain.

Methods

RCTs using CAM interventions for cancer-related pain were abstracted using Medline, EMBASE, CINAHL, AMED, and Cochrane database.

Results

Eighteen trials were identified (eight poor, three intermediate, and seven high quality based on Jadad score), with a total of 1,499 patients. Median sample size was 53 patients, and median intervention duration was 45 days. All studies were from single institutions, four had sample size justification, and none reported any adverse effects. Seven trials reported significant benefit for the following CAM therapies: acupuncture (n = 1), support groups (n = 2), hypnosis (n = 1), relaxation/imagery (n = 2), and herbal supplement/HESA-A (n = 1, but study was of low quality without control data). Seven studies reported immediate postintervention or short-term benefit of the following CAM interventions: acupuncture (n = 2), music (n = 1), herbal supplement/Ai-Tong-Ping (n = 1), massage (n = 1), and healing touch (n = 2). Four studies reported no benefit of CAM interventions (music, n = 2; massage, n = 2) in reducing cancer pain compared with a control arm.

Conclusion

There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.
Phase II Trial of Amrubicin for Treatment of Refractory or Relapsed Small-Cell Lung Cancer: Thoracic Oncology Research Group Study 0301
Authors: Onoda Sayaka , Masuda Noriyuki , Seto Takashi , Eguchi Kenji , Takiguchi Yuichi , Isobe Hiroshi , Okamoto Hiroaki , Ogura Takashi , Yokoyama Akira , Seki Nobuhiko , Asaka-Amano Yoshiko , Harada Masao , Tagawa Akihiro , Kunikane Hiroshi , Yokoba Masanori , Uematsu Kazutsugu , Kuriyama Takayuki , Kuroiwa Yumi , Watanabe Koshiro
Published: November 2006

Purpose

This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC).

Patients and Methods

SCLC patients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression ≥ 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks.

Results

Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively.

Conclusion

Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.
Reciprocal Cross Talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors Regulates GnRH Receptor Expression and Differential Gonadotropin Secretion
Authors: Naor Zvi , Jabbour Henry N. , Naidich Michal , Pawson Adam J. , Morgan Kevin , Battersby Sharon , Millar Michael R. , Brown Pamela , Millar Robert P.
Published: December 2006

The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3′-kinase/MAPK pathway in the LβT2 gonadotrope cell line. We then demonstrated that PGF2α and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF2α, but not PGI2 or PGE2, reduced GnRH-induction of LHβ gene expression, but not the α-gonadotropin subunit or the FSHβ subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF2α, but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF2α-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer.
Mechanical energy fluctuations during hill walking: the effects of slope on inverted pendulum exchange
Authors: Gottschall Jinger S. , Kram Rodger
Published: December 2006

Humans and other animals exchange gravitational potential energy (GPE) and kinetic energy (KE) of the center of mass during level walking. How effective is this energy exchange during downhill and uphill walking? Based on previous reports and our own reasoning, we expected that during downhill walking, the possibility for mechanical energy exchange would be enhanced and during uphill walking, the possibility for exchange would be reduced. We measured the fluctuations of the mechanical energies for five men and five women walking at 1.25 m s-1. Subjects walked on the level, downhill, and uphill on a force measuring treadmill mounted at 3°, 6° and 9°. We evaluated energy exchange during the single support period based on the GPE and KE fluctuation factors of phase relationship, relative magnitude and extent of symmetry. As expected, during level walking, the GPE and KE curves were out of phase, of similar magnitude, and nearly mirror images so that the fluctuations in combined (GPE+KE) energy were attenuated. During downhill walking, the fluctuations in the combined energy of the center of mass were smaller than those on the level, i.e. mechanical energy exchange was more effective. During uphill walking, the fluctuations in the combined energy of the center of mass were larger than those on the level, i.e. mechanical energy exchange was less effective. Mechanical energy exchange occurred during downhill, level and uphill walking, but it was most effective during downhill walking.
Males also have their time of the month! Cyclic disposal of old spermatophores, timed by the molt cycle, in a marine shrimp
Authors: Parnes Shmuel , Raviv Shaul , Shechter Asaf , Sagi Amir
Published: December 2006

That sexually mature females go through hormonally regulated reproductive cycles is a well-established phenomenon in sexually reproducing organisms. Males, on the other hand, are commonly regarded as being continuously ready to mate. `Programmed sperm degradation' on a periodic basis or an innate sperm`expiry date' have never been shown. This manuscript describes a newly discovered molt-dependent mechanism by which old sperm is periodically removed from the reproductive system of male Litopenaeus vannamei shrimp. Firstly, it is shown that the spermatophores of males held in captivity become progressively melanized, a process that eventually renders them impotent. Then, by using melanin specks as a color marker, it is demonstrated that this phenomenon can be delayed and even reversed as long as the males remain sexually active. Lastly and most importantly, it is shown that male shrimp go through reproductive cycles that are strictly associated with their molt cycles, which, in turn, are hormonally regulated. Intact intermolt spermatophores disappeared about 12 h premolt, and a new pair of spermatophores appeared in the ampoules the day after the males had molted. This phenomenon was observed in an almost constant portion of males, both those in an all-male population and those in mixed male/female populations,even during the times that the females of those populations were not vitellogenically active. To the best of our knowledge, this is the first report of males of any animal species exhibiting endogenous reproductive cycles, as do females, and of the finding that spermatozoa have a predetermined expiry date, a feature that may possibly contribute to male fitness.
Ancestry of neuronal monoamine transporters in the Metazoa
Authors: Caveney Stanley , Cladman Wendy , Verellen LouAnn , Donly Cam
Published: December 2006

Selective Na+-dependent re-uptake of biogenic monoamines at mammalian nerve synapses is accomplished by three types of solute-linked carrier family 6 (SLC6) membrane transporter with high affinity for serotonin(SERTs), dopamine (DATs) and norepinephrine (NETs). An additional SLC6 monoamine transporter (OAT), is responsible for the selective uptake of the phenolamines octopamine and tyramine by insect neurons. We have characterized a similar high-affinity phenoloamine transporter expressed in the CNS of the earthworm Lumbricus terrestris. Phylogenetic analysis of its protein sequence clusters it with both arthropod phenolamine and chordate catecholamine transporters. To clarify the relationships among metazoan monoamine transporters we identified representatives in the major branches of metazoan evolution by polymerase chain reaction (PCR)-amplifying conserved cDNA fragments from isolated nervous tissue and by analyzing available genomic data. Analysis of conserved motifs in the sequence data suggest that the presumed common ancestor of modern-day Bilateria expressed at least three functionally distinct monoamine transporters in its nervous system: a SERT currently found throughout bilaterian phyla, a DAT now restricted in distribution to protostome invertebrates and echinoderms and a third monoamine transporter (MAT), widely represented in contemporary Bilateria, that is selective for catecholamines and/or phenolamines. Chordate DATs, NETs,epinephrine transporters (ETs) and arthropod and annelid OATs all belong to the MAT clade. Contemporary invertebrate and chordate DATs belong to different SLC6 clades. Furthermore, the genes for dopamine and norepinephrine transporters of vertebrates are paralogous, apparently having arisen through duplication of an invertebrate MAT gene after the loss of an invertebrate-type DAT gene in a basal protochordate.
Dual leading-edge vortices on flapping wings
Authors: Lu Yuan , Shen Gong Xin , Lai Guo Jun
Published: December 2006

An experimental investigation was performed with two aims: (1) to clarify the existence of the dual leading-edge vortices (i.e. two vortices with the same sense of rotation located close to the leading edge above the leeward wing surface) observed on flapping wings in previous studies; (2) to study systematically the influences of kinematic and geometric parameters on such a vortical structure. Based on a scaled-up electromechanical model flapping in a water tank, the leading-edge vortex (LEV) cores were visualized viadye flow visualization, and the detailed sub-structures of LEV were revealed through digital particle image velocimetry (DPIV) with high spatial resolution. Five wing aspect ratios (AR) (1.3, 3.5, 5.8, 7.5 and 10),eight mid-stroke angles of attack (αm) (10-80°), and six Reynolds numbers (Re) (160-3200) were examined. In addition, the well-studied case of the fruit fly Drosophila was re-examined.

The results confirm for the first time the existence of dual LEVs on flapping wings. The sectional flow structure resembles the dual-vortex observed on non-slender delta wings. Insensitive to AR, a dual LEV system such as this could be created when αm and Rereached certain high levels. The primary vortex was attached to the wing,while at the outer wing the minor vortex shed, generating a same-sense vortex behind.
Micromilling strategies for machining thin features
Authors: Popov K , Dimov S , Pham D T , Ivanov A
Published: November 2006

Micromilling of metal structures with ‘thin’ features represents a major challenge towards broadening the use of this technology in a range of microengineering applications, for example in producing multi-channel microstructures, housing for mechanical microdevices, and surgical instruments. The most common thin features seen in microengineering products are ribs and webs.

This research identifies the main factors affecting the reliability of micromilling technology when employed for the machining of microcomponents incorporating thin features. The general principles that should be followed in designing machining strategies for such features are discussed in this article. Taking these general principles into account, new strategies are proposed to reduce the negative effects of identified factors on part quality and, at the same time, to overcome some of the problems associated with the use of conventional machining strategies for micromilling of ribs and webs. To implement and verify them, initially the milling operations were programmed manually, and then a special CAM module was developed for their automatic generation. Finally, this article reports the validation of the proposed strategies for machining thin features, which was carried out on a specially designed test part.
Miniaturization of injection abrasive water jet machining process
Authors: Orbanic H , Jurisevic B , Kramar D , Grah M , Junkar M
Published: November 2006

This contribution presents the possibilities of applying abrasive water jet (AWJ) technology for multi-material micromanufacture. The working principles of injection and suspension AWJ systems are presented. Characteristics of this technology, such as the ability to machine virtually any kind of material and the absence of a relevant heat-affected zone, are given, especially those from which the production of microcomponents can benefit. A few attempts to miniaturize the AWJ machining process are described in the state-of-the-art preview. In order to develop and improve the AWJ as a microtool, a numerical simulation based on the finite element analysis is introduced to evaluate the effect of the size abrasive particles and the process efficiency of microsized AWJ. An ongoing project in which an improved mini AWJ cutting head is being developed, is presented. Finally, the possible fields of application are given, including a case study on the machining of miniaturized heat sinks.
Comparison between microfabrication technologies for metal tooling
Authors: Uriarte L , Herrero A , Ivanov A , Oosterling H , Staemmler L , Tang P T , Allen D
Published: November 2006

This paper is based on the information gathered within the Multi-Material Micro-Manufacture (4M) Network activities in the Processing of Metals Division (Task 7.2 ‘Tooling’) ( www.4m-net.org ). The aim of the task involves a systematic analysis of the partners' expertise in different microtechnologies for processing tooling inserts made of metal. The following technologies have been analysed: micromilling, micro-electrodischarge machining (EDM, including wire-EDM, sinking-EDM, and EDM-milling), laser micromachining, electroforming, and electrochemical milling (ECF) (an electrochemical machining innovative process proposed by HSG-IMAT). Considered tool-insert materials are nickel for electroforming, stainless steel for ECF, and tool steel (AISI H13) for all other processes. Typical features (ribs, channels, pins, and holes) required by micro-optics, microfluidics, and sensor and actuator applications have been selected to form the benchmark part and to carry out this analysis.

The results provide a global comparison between the micromanufacturing processes mentioned earlier in terms of technical capabilities and cost effectiveness of different feature machinings. As a second result, the current limitations of these technologies concerning feature sizes, surface finish, aspect ratios, etc. have been identified. The main conclusion drawn is the absence of a consolidated technology to produce three-dimensional free-form shapes smaller than 100–200 μm to date.
Laser milling: Modelling crater and surface formation
Authors: Dobrev T , Dimov S S , Thomas A J
Published: November 2006

In pulsed laser-material removal systems, it is very important to understand the physical phenomena that take place during the laser ablation process. A two-dimensional, theoretical model is developed to investigate the crater formation on a metal target by a microsecond laser pulse. The model takes into account the absorption of the laser light and heating and vapourization of the target, including an adjustment to compensate for the change of state. A simple numerical technique is employed to describe the major physical processes taking part in the laser milling process. The temperature distribution in the target material during the pulse duration is analysed. The effect of the laser fluence on the resulting crater is investigated in detail. The proposed simulation model was validated experimentally for laser-material interactions between a microsecond Nd:YAG laser (λ = 1064 nm) and two different tooling materials. The measured crater depths are in agreement with the model. In addition, an analytical approach is discussed for studying the effects of crater profiles and different machining strategies on the surface formation and the resulting surface quality during the laser milling process. This approach can be employed as a tool for optimizing the process and thus broaden its use in a range of microstructuring applications. The research reported in this paper contributes to a better understanding of microstructuring capabilities of the laser milling process.
Failure and volume fraction dependent mechanical properties of composite sensors and actuators
Authors: Bowen C R , Dent A C , Nelson L J , Stevens R , Cain M G , Stewart M
Published: November 2006

Composite actuators and sensors manufactured by combining a ferroelectric ceramic such as lead zirconate titanate and a passive phase such as a polymer are used in a variety of applications including SONAR, vibration damping, change of structural shape (morphing), and structural health monitoring. The composite route provides specific advantages, including tailored piezoelectric response, high strain, a degree of flexibility, and increased damage tolerance compared with conventional dense monolithic ceramic materials. For piezoelectric fibre composites, where fine-scale brittle ceramic fibres of 40–800 μm diameter are introduced into a ductile polymer matrix, the composite strength and failure mechanism ultimately depend on the mechanical properties of each phase and their volume fraction. This article examines the mechanical properties of piezoelectric fibres and the matrix phase and discusses the possible influence of fibre volume fraction on mechanical properties and failure mechanism of the composite. The data are of particular use in determining the failure stress, failure strain, and failure mechanism of composite actuators and sensors subjected to high levels of stress, for example, in applications where such devices are embedded into host structures.
Rapid prototyping tools and methods for all-Topas® cyclic olefin copolymer fluidic microsystems
Authors: Bundgaard F , Perozziello G , Geschke O
Published: November 2006

Topas®, the cyclic olefin copolymer, from Topas Advanced Polymers GmbH has a number of advantages over polymers such as poly(methylmethacrylate), polydimethylsiloxane, and polycarbonate traditionally used in fluid microsystem manufacturing, such as low water absorption, high chemical resistance, good machinability, and good optical properties. A number of different processes for rapid and low-cost prototyping of all-Topas microfluidic systems, made with desktop machinery, are presented. Among the processes are micromilling of fluidic structures with a width down to 25 μm and sealing of fluidic channels by thermal bonding or laser bonding, using a thin, spin-coated layer of carbon particles between the Topas substrate and the lid to absorb the laser light.
Design study of a capacitive pressure sensor in non-silicon materials
Authors: Meuwissen M H H , Veninga E P , Tijdink M W W J , Meijerink M G H
Published: November 2006

This article reports on the design of a capacitive pressure sensor fabricated in non-silicon materials. The sensor consists of a thin membrane placed parallel to a rigid reference plane. The membrane and the reference plane act as two electrodes of a capacitor. Deflection of the membrane due to pressure differences results in changes in capacity. These capacity changes are processed to calculate the pressure on the membrane.

Several thermo-mechanical performance aspects of the sensor were addressed during the design stage. Promising variants of the sensor were built and subjected to mechanical tests. In addition, numerical techniques were utilized to assess the performance of certain variants before building and testing physical prototypes.

The application of this combination of physical experiments and numerical simulations is demonstrated for the selection of a suitable membrane material and membrane dimensions (diameter and thickness), the specification of the substrate thickness in case the sensor is mounted on the backside of an electronics housing, and the selection of a suitable solder interconnect material and interconnect dimensions. A critical aspect in the latter case was the creep behaviour of the solder material, which had to be minimized in order to obtain an acceptable long-term accuracy of the sensor.

A sensor membrane and an interconnect design were finally specified on the basis of the outcome of the design studies. It proved to meet the functional demands imposed by the targeted application on a laboratory scale. It will be subjected to reliability and lifetime assessment tests in a next phase.