Characterizing Deficit Accumulation Among Gulf War Era Veterans.

BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.

Gabapentinoids for Pain: A Review of Published Comparative Effectiveness Trials and Data Submitted to the FDA for Approval.

Use of the gabapentinoids for pain continues to increase. In 2018, the US Food and Drug Administration (FDA) strengthened the warnings for both gabapentin and pregabalin to emphasize the central nervous system side effects and the risk of respiratory depression, especially when combined with other centrally acting drugs. We reviewed the published comparative effectiveness literature for gabapentinoids for pain as well as all trials (published and unpublished) used by the FDA for the approval of the five pain indications for these agents (one for gabapentin, four for pregabalin). Among the findings of interest are the fact that the FDA rejected the application for gabapentin for diabetic peripheral neuropathy based on the risk versus benefit profile of that drug in the clinical trials that were submitted by the manufacturer. Additionally, both the comparative effectiveness trials as well as the studies used by the FDA tend to be short in duration and show only modest pain benefits for the gabapentinoids. The placebo response in these trials was frequently one-third to one-half as great as the pain benefit demonstrated by the gabapentinoid. Based on the available clinical trial evidence, we feel prescribers should be cautious when using gabapentinoids for pain, particularly when using these agents for a prolonged period or when combined with other, centrally acting agents.

Self-reported gastrointestinal disorders among veterans with gulf war illness with and without posttraumatic stress disorder.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Removal of heavy metals from acid mine drainage (AMD) using coal fly ash, natural clinker and synthetic zeolites.

Acid mine drainage (AMD) is a widespread environmental problem associated with both working and abandoned mining operations, resulting from the microbial oxidation of pyrite in presence of water and air, affording an acidic solution that contains toxic metal ions. The generation of AMD and release of dissolved heavy metals is an important concern facing the mining industry. The present study aimed at evaluating the use of low-cost sorbents like coal fly ash, natural clinker and synthetic zeolites to clean-up AMD generated at the Parys Mountain copper-lead-zinc deposit, Anglesey (North Wales), and to remove heavy metals and ammonium from AMD. pH played a very important role in the sorption/removal of the contaminants and a higher adsorbent ratio in the treatment of AMD promoted the increase of the pH, particularly using natural clinker-based faujasite (7.70-9.43) and the reduction of metal concentration. Na-phillipsite showed a lower efficiency as compared to that of faujasite. Selectivity of faujasite for metal removal was, in decreasing order, Fe>As>Pb>Zn>Cu>Ni>Cr. Based on these results, the use of these materials has the potential to provide improved methods for the treatment of AMD.

Can Strain Dependent Inhibition of Cross-Bridge Binding Explain Shifts in Optimum Muscle Length?

Skeletal muscle force is generated by cross-bridge interactions between the overlapping contractile proteins, actin and myosin. The geometry of this overlap gives us the force-length relationship in which maximum isometric force is generated at an intermediate, optimum, length. However, the force-length relationship is not constant; optimum length increases with decreasing muscle activation. This effect is not predicted from actin-myosin overlap. Here we present evidence that this activation-dependent shift in optimum length may be due to a series compliance within muscles. As muscles generate force during fixed-end contractions, fibers shorten against series compliance until forces equilibrate and they become isometric. Shortening against series-compliance is proportional to activation, and creates conditions under which shortening-induced force depression may suppress full force development. Greater shortening will result in greater force depression. Hence, optimum length may decrease as activation rises due to greater fiber shortening. We discuss explanations of such history dependence, giving a review of previously proposed processes and suggesting a novel mechanistic explanation for the most likely candidate process based on tropomyosin kinetics. We suggest this mechanism could change the relationship between actin-myosin overlap and cross-bridge binding potential, not only depressing force at any given length, but also altering the relationship between force and length. This would have major consequences for our understanding of in vivo muscle performance.

Spatial Scale and Structural Heterogeneity in Skeletal Muscle Performance.

Biological movement is an inherently dynamic process, characterized by large spatiotemporal variations in force and mechanical energy. Molecular level interactions between the contractile proteins actin and myosin do work, generating forces and transmitting them to the environment via the muscle's and supporting tissues' complex structures. Most existing theories of muscle contraction are derived from observations of muscle performance under simple, tightly controlled, in vitro or in situ conditions. These theories provide predictive power that falls off as we examine the more complicated action and movement regimes seen in biological movement. Our early and heavy focus on actin and myosin interactions have lead us to overlook other interactions and sources of force regulation. It increasingly appears that the structural heterogeneity, and micro-to-macro spatial scales of the force transmission pathways that exist between actin and myosin and the environment, determine muscle performance in ways that manifest most clearly under the dynamic conditions occurring during biological movement. Considering these interactions, along with the dynamics of force transmission tissues, actuators, and environmental physics have enriched our understanding of biological motion and force generation. This symposium brings together diverse investigators to consolidate our understanding of the role of spatial scale and structural heterogeneity role in muscle performance, with the hope of updating frameworks for understanding muscle contraction and predicting muscle performance in biological movement.

Computational characterisation of dried and hydrated graphene oxide membranes.

A multi-step molecular dynamics procedure was developed to construct fully flexible atomistic models of graphene oxide (GO) membranes. The method of preparation replicates the experimental synthesis of the material; i.e. the flow-directed self-assembly of individual flakes onto a substrate or filter. A total of 180 GO membrane models were prepared with water contents varying between 0 and 20%, providing an insight into changes in the membrane's interlayer distance with swelling. Membranes with 15% water content have an average interlayer distance (0.80 nm), bulk density (1.77 g cm-3) and tensile modulus (18.1 GPa) in excellent agreement with the experimental literature, demonstrating that air-dried membranes have 15% water content. The models reveal the intrinsic structural heterogeneity and complex morphology of GO membranes. This feature has previously been unaccounted for in both experimental interpretations and GO nanopore models, which often use pre-defined and idealised 2D geometries. Completely dried membranes have considerable free pore volume. This observation explains the modest change in interlayer distance (0.02 nm) as the membrane's water content is increased from 0% to 10% compared to a much more significant change (0.12 nm) as the water content is increased from 10% to 20%. Combined with this new understanding of membrane swelling, the availability of such representative models opens the possibility of the molecular-level design of GO membranes for a variety of applications, such as gaseous and aqueous separations.

Autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma and CNS involvement: those transplanted with active CNS disease have a poor outcome--a report by the European Bone Marrow Transplant Lymphoma Registry.

PURPOSE: CNS involvement of non-Hodgkin's lymphoma (NHL) has always been considered a poor prognostic factor in relation to survival with conventional therapy. However, its effect on the outcome of autologous bone marrow transplantation (ABMT) has not been assessed. We examined this using data from the European Bone Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: One thousand four hundred sixty-four patients with NHL have been reported to the EBMT registry, of whom 62 had CNS involvement. Patients were divided into those who were clear of CNS disease at the time of ABMT and those who were not. Response, complications, and outcome to ABMT were analyzed, as were details of CNS diagnosis, treatment, and prophylaxis. RESULTS: Status at transplant was the only factor that significantly affected outcome of ABMT on univariate analysis (P = .03). The progression-free survival (PFS) rate of the group that had no CNS involvement at ABMT was 42% at 5 years, compared with 27% in a group of stage IV NHL patients without CNS disease (matched for status at transplant and histology). There were four of 45 (8.9%) toxic deaths. The PFS rate of the group that had CNS involvement at ABMT was 9% at a median follow-up time of 71 months, which was significantly different (P = .001) from that of the other group. There were five of 17 (29.4%) toxic deaths (P = .043). Patients who had CNS involvement at diagnosis, as compared with relapse, and those treated with both intrathecal chemotherapy and irradiation had a better outcome. CONCLUSION: The presence of CNS disease before ABMT but not present at transplant does not adversely affect the outcome of ABMT. In contrast, patients with CNS involvement at the time of ABMT have a poor prognosis, although a small number survive in complete remission (CR).

Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.

PURPOSE: We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study. PATIENTS AND METHODS: Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. RESULTS: The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups. CONCLUSION: This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.

Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry.

PURPOSE: The use of in vitro purging of bone marrow in autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) has been a controversial issue; its benefit is as yet unproven. Its effect on the clinical outcome of ABMT in these patients is still unclear. We look at this issue using data from the European Blood and Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: Seventeen hundred twenty-six patients with NHL have been reported to the EBMT registry, of whom 270 had bone marrow purged at transplant. Two hundred twenty-four of these patients were compared with a case-matched group of 224 unpurged patients who had undergone the same procedure. The case matching was made following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. Response, complications, and outcome in ABMT were analyzed. RESULTS: Time to hematologic engraftment, response to ABMT, and number of procedure-related deaths were similar in purged and unpurged patients. The overall survival (OS) rate was 54% at 5 years in purged patients and 48.3% in unpurged patients (P = .1813). The PFS rate was 44.3% and 44.6%, respectively (P = .1961). Patterns of relapse, including bone marrow relapse, were similar in both groups. Patients with low-grade lymphoma did not have a significantly improved PFS if the bone marrow was purged (P = .1757); however, they did have a significantly improved OS (P = .00184). This increased OS was found to be associated with non-totalbody irradiation (TBI) conditioning and also with the purged patients undergoing transplantation at large transplant centers (P = .0016). CONCLUSION: Purging of bone marrow in ABMT for NHL does not affect the rate of hematologic engraftment or risk of procedure-related death (PRD). There is no significant difference in PFS for patients whose bone marrow is purged as compared with unpurged.

High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry.

PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin's lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P =.0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P =.939 and P =.438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.

Back-up bone marrow is frequently ineffective in patients with poor peripheral-blood stem-cell mobilization.

PURPOSE: To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed. PATIENTS AND METHODS: The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed. RESULTS: In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (> 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths. CONCLUSION: This study shows that delayed hematologic recovery is frequent if less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy, particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality in this latter group is high. In most patients whose PBSC collection contains less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve engraftment, which suggests that poor PBSC mobilization usually indicates poor marrow function.

A prospective, randomized study of endometrial telomerase during the menstrual cycle.

The purpose of this study was to characterize telomerase activity during the menstrual cycle, focusing on the luteal phase. A total of 84 endometrial biopsy samples were obtained from 72 participants. Daily urinary LH testing (OvuQuick, Quidel) was used to establish the day of the LH rise, and participants were randomized to return during the secretory phase. Twelve women returned on the identical day during the luteal phase of a subsequent cycle to allow intercycle comparisons of telomerase activity. Telomerase activity was evaluated using a modified TRAP-eze (Intergen) detection protocol. At the time of each endometrial biopsy, serum estrogen and progesterone were measured. Proliferative phase endometrium showed high telomerase activity. At the onset of the luteal phase telomerase activity was high, but it decreased during the early luteal phase, disappeared by the midluteal phase (6 d after LH surge detected), and then rose to moderate levels in the late luteal phase beginning on luteal d 10. Serum progesterone levels were inversely related to telomerase activity. In conclusion, endometrial telomerase activity is dynamic: high during the proliferative phase but inhibited during the midsecretory phase of the menstrual cycle. The timing of expression coincides with the rise and fall of progesterone levels and the time period of maximal uterine receptivity for embryo implantation. This supports a relationship between sex steroid levels and telomerase regulation.

Epidemiology of dysphoria and depression in an elderly population.

The authors surveyed 997 elderly people living in the community and found that the rate of significant dysphoric symptomatology was 14.7%. Forty-five (4.5%) of these individuals suffered from dysphoric symptoms only, and 37 (3.7%) had symptoms of a major depressive disorder. Eighteen (1.8%) suffered from symptoms of primary depressive disorder and 19 (1.9%) from symptoms of secondary depressive disorder. Sixty-five (6.5%) had depressive symptoms associated with impaired physical health. The frequency of widowhood, impairment in social resources, and impairment in economic resources was greater for individuals with symptoms of a major depressive disorder. The entire sample used psychiatric services at a very low rate.

Influence of primary closure of the pericardium after open-heart surgery on the frequency of tamponade, postcardiotomy syndrome, and pulmonary complications.

Experiences with primary closure of the pericardium in a series of 100 patients undergoing open-heart operations are described. The pericardium was kept under tension during the operation to minimize shrinkage and permit closure at the end of the procedure. In 28 patients one pleural space was opened for drainage, whereas in 72 patients intra- and extrapericardial sumps alone were used for drainage. Measurements of sump drainage revealed that most postoperative bleeding originates from outside the pericardium. There were no instances of cardiac tamponade although 19 patients lost more than 1 L. of blood after operation and 5 required reoperation for hemorrhage. Transpleural drainage tubes were shown to be ineffective and in addition were associated with a fourfold increase in postcardiotomy syndrome and a significantly greater frequency of pleural effusion and atelectasis when compared to the use of mediastinal sump drainage alone. We have concluded that closing the pericardium and using mediastinal sump drainage minimizes the risk of cardiac tamponade and allows early localization of the site of postoperative bledding. Another advantage of pericardial closure and drainage is that postoperative adhesions and postcardiotomy syndrome will be less significant. As a consequence the danger of injuring the heart in a subsequent operation is lessened.

A case of EBV-associated lymphoproliferative disease following high-dose therapy and CD34-purified autologous peripheral blood progenitor cell transplantation.

A fatal case of EBV-associated lymphoproliferative disorder arising after a CD34-selected autologous peripheral blood stem cell transplant is reported in a patient with multiple myeloma in first plateau phase. It is suggested that this is likely to be a consequence of the accessory cell depletion associated with the CD34+ cell purification and it is recommended that a source of autologous T cells is stored before transplantation to be used if a severe opportunistic infection or EBV lymphoma arises post-transplantation.

Evaluation of clinical scale CD34+ cell purification: experience of 71 immunoaffinity column procedures.

Seventy-one mobilised PBSC collections were subject to CD34+ cell purification using the CEPRATE SC stem cell concentration system. The overall median purity of CD34+ cells was 69% (6-93%). CD34+ cell, and GM-CFC recoveries were 52% (8-107%) and 36% (3-118%). Purity was logarithmically related to the input percentage of CD34+ cells and starting requirements were established of 1% CD34 cell content for optimal purity and a minimum of 2 x 10(6)/kg CD34+ cells to ensure recovery of our minimum engraftment threshold of 1 x 10(6)/kg CD34+ cells. Reduction of the washing steps reduced non-specific cell losses and shortened the procedure but did not affect progenitor cell recovery. Purified CD34+ cells were reinfused following high-dose therapy in 35 patients. The median time to neutrophil recovery of 0.5 x 10(9)/l was 12 (10-23) days and to the attainment of platelet independence was 13 (7-100) days. The risks of delayed platelet recovery were related to the CD34+ cell dose infused and were identical to the risks when non-purified PBSC collections were used. In conclusion, purification of CD34+ cells using the CEPRATE device is reliable and the purified product results in prompt engraftment. The cell losses that occur do however restrict its use in many patients.

Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

Therapeutic electromagnetic field effects on angiogenesis and tumor growth.

BACKGROUND: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammary adenocarcinoma cells in C3H/HeJ mice. MATERIALS AND METHODS: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 pulses per second pulsating magnetic field. Tumor growth was assessed throughout the treatment period. The extent of tumor vascularization was evaluated by immunohistochemical staining for CD31. RESULTS: Exposure to TEMF significantly reduced tumor growth, significantly reduced the percentage of area stained for CD31 indicating a reduction in the extent of vascularization and there was a concomitant increase in the extent of tumor necrosis. CONCLUSION: A novel TEMF treatment safely reduced growth and vascularization of implanted breast cancers in mice. IMPLICATION: TEMF may prove a useful adjuvant to increase the therapeutic index of conventional cancer therapy.