Effectiveness of selective dorsal rhizotomy in 2 patients with progressive spasticity due to neurodegenerative disease

Selective dorsal rhizotomy at the lumbar level is a neurosurgical procedure, which reduces spasticity in the legs. Its effect has mainly been studied in children with spastic cerebral palsy. Little is known about the outcome of selective dorsal rhizotomy in patients with neurodegenerative disorders. We report the clinical course after selective dorsal rhizotomy in 2 patients with progressive spasticity. Leg spasticity was effectively and persistently reduced in both patients, facilitating care and improving sitting comfort. However, spasticity of the arms and other motor disturbances, such as spontaneous extension spasms and the ataxia, increased gradually in time. Selective dorsal rhizotomy leads to a disappearance of leg spasticity in patients with a neurodegenerative disease. Other motor signs are not influenced and may increase due to the progressive nature of the underlying disease.

Motesanib diphosphate in progressive differentiated thyroid cancer

BACKGROUND: The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT. METHODS: In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration. RESULTS: Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective response rate was 14%. Stable disease was achieved in 67% of the patients, and stable disease was maintained for 24 weeks or longer in 35%; 8% had progressive disease as the best response. The Kaplan-Meier estimate of the median duration of the response was 32 weeks (the lower limit of the 95% confidence interval [CI] was 24; the upper limit could not be estimated because of an insufficient number of events); the estimate of median progression-free survival was 40 weeks (95% CI, 32 to 50). Among the 75 patients in whom thyroglobulin analysis was performed, 81% had decreased serum thyroglobulin concentrations during treatment, as compared with baseline levels. The most common treatment-related adverse events were diarrhea (in 59% of the patients), hypertension (56%), fatigue (46%), and weight loss (40%). CONCLUSIONS: Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive. (ClinicalTrials.gov number, NCT00121628.)

Governor Forrest Anderson’s Leadership & Political Acumen -- Alec Hansen “In the Crucible of Change”

Montana Governor Forrest Anderson was perhaps the most experienced and qualified person ever to be elected as Governor of Montana. Having previously served as a county attorney, a member of the legislature, a Supreme Court Justice, and twelve years as Attorney General, Anderson roared to a large victory in 1968 over the Incumbent GOP Governor Tim Babcock. Though the progressive change period in Montana began a few years earlier, Anderson’s 1968 win catapulted progressive policy-making into the mainstream of Montana political and governmental affairs. He used his unique skills and leadership to craftily architect the reorganization of the executive branch which had been kept weak since statehood so that the peoples’ government would not be able to challenge corporations who so dominated Montana. Anderson, whose “Pay More, What For?” campaign slogan strongly separated him from Tim Babcock and the GOP on the sales tax issue, not only beat back the regressive sales tax in the 1968 election, but oversaw its demise at the polls in 1971, shaping politics in Montana for decades to come. Anderson also was a strong proponent of the concept of a new Montana Constitution and contributed strategically to its calling and passage. Anderson served only one term as Governor for health reasons, but made those four years a launch pad for progressive politics and government in Montana. In this film, Alec Hansen, Special Assistant to Governor Anderson, provides an insider’s perspective as he reflects on the unique way in which Governor Anderson got things done at this critical period “In the Crucible of Change.” Alec Hansen is best known in Montana political and governmental circles as the long-time chief of the Montana League of Cities and Towns, but he cut his teeth in public service with Governor Forrest Anderson. Alec was born in Butte in 1941, attended local schools graduating from Butte High in 1959. After several years working as a miner and warehouseman for the Anaconda Company in Butte, he attended UM and graduated in History and Political Science in 1966. He joined the U.S. Navy and served with amphibious forces in Vietnam. After discharge from the Navy in 1968, he worked as a news and sports reporter for The Montana Standard in Butte until in September of 1969 he joined Governor Anderson as a Special Assistant focused on press, communications and speech-writing. Alec has noted that drafts were turned into pure Forrest Anderson remarks by the man himself. He learned at the knee of “The Fox” for the rest of Anderson’s term and continued with Governor Tom Judge for two years before returning to Butte to work for the Anaconda Company as the Director of Communications for Montana operations. In 1978, after Anaconda was acquired by the Atlantic Richfield Company, Alec went to work in February for U.S. Senator Paul Hatfield in Washington D.C., leaving after Hatfield’s primary election loss in June 1978. He went back to work for Gov. Judge, remaining until the end of 1980. In 1981 Alec worked as a contract lobbyist and news and sports reporter for the Associated Press in Helena. In 1982, the Montana League of Cities and Towns hired him as Executive Director, a position he held until retirement in 2014. Alec and his wife Colleen, are the parents of two grown children, with one grandson.

Past is Prologue: Montana’s Historic Women’s Movement Re-emerges in the Progressive 1970s -- Dorothy Bradley, Marilyn Wessel & Jane Jelinski “In the Crucible of Change”

One-hundred years ago, in 1914, male voters in Montana (MT) extended suffrage (voting rights) to women six years before the 19th Amendment to the US Constitution was ratified and provided that right to women in all states. The long struggle for women’s suffrage was energized in the progressive era and Jeanette Rankin of Missoula emerged as a leader of the campaign; in 1912 both major MT political party platforms supported women suffrage. In the 1914 election, 41,000 male voters supported woman suffrage while nearly 38,000 opposed it. MT was not only ahead of the curve on women suffrage, but just two years later in 1916 elected Jeanette Rankin as the first woman ever elected to the United States Congress. Rankin became a national leader for women's equality. In her commitment to equality, she opposed US entry into World War I, partially because she said she could not support men being made to go to war if women were not allowed to serve alongside them. During MT’s initial progressive era, women in MT not only pursued equality for themselves (the MT Legislature passed an equal pay act in 1919), but pursued other social improvements, such as temperance/prohibition. Well-known national women leaders such as Carrie Nation and others found a welcome in MT during the period. Women's role in the trade union movement was evidenced in MT by the creation of the Women's Protective Union in Butte, the first union in America dedicated solely to women workers. But Rankin’s defeat following her vote against World War I was used as a way for opponents to advocate a conservative, traditionalist perspective on women's rights in MT. Just as we then entered a period in MT where the “copper collar” was tightened around MT economically and politically by the Anaconda Company and its allies, we also found a different kind of conservative, traditionalist collar tightened around the necks of MT women. The recognition of women's role during World War II, represented by “Rosie the Riveter,” made it more difficult for that conservative, traditionalist approach to be forever maintained. In addition, women's role in MT agriculture – family farms and ranches -- spoke strongly to the concept of equality, as farm wives were clearly active partners in the agricultural enterprises. But rural MT was, by and large, the bastion of conservative values relative to the position of women in society. As the period of “In the Crucible of Change” began, the 1965 MT Legislature included only three women. In 1967 and 1969 only one woman legislator served. In 1971 the number went up to two, including one of our guests, Dorothy Bradley. It was only after the Constitutional Convention, which featured 19 women delegates, that the barrier was broken. The 1973 Legislature saw 9 women elected. The 1975 and 1977 sessions had 14 women legislators; 15 were elected for the 1979 session. At that time progressive women and men in the Legislature helped implement the equality provisions of the new MT Constitution, ratified the federal Equal Rights Amendment in 1974, and held back national and local conservatives forces which sought in later Legislatures to repeal that ratification. As with the national movement at the time, MT women sought and often succeeded in adopting legal mechanisms that protected women’s equality, while full equality in the external world remained (and remains) a treasured objective. The story of the re-emergence of Montana’s women’s movement in the 1970s is discussed in this chapter by three very successful and prominent women who were directly involved in the effort: Dorothy Bradley, Marilyn Wessel, and Jane Jelinski. Their recollections of the political, sociological and cultural path Montana women pursued in the 1970s and the challenges and opposition they faced provide an insider’s perspective of the battle for equality for women under the Big Sky “In the Crucible of Change.” Dorothy Bradley grew up in Bozeman, Montana; received her Bachelor of Arts Phi Beta Kappa from Colorado College, Colorado Springs, in 1969 with a Distinction in Anthropology; and her Juris Doctor from American University in Washington, D.C., in 1983. In 1970, at the age of 22, following the first Earth Day and running on an environmental platform, Ms. Bradley won a seat in the 1971 Montana House of Representatives where she served as the youngest member and only woman. Bradley established a record of achievement on environmental & progressive legislation for four terms, before giving up the seat to run a strong second to Pat Williams for the Democratic nomination for an open seat in Montana’s Western Congressional District. After becoming an attorney and an expert on water law, she returned to the Legislature for 4 more terms in the mid-to-late 1980s. Serving a total of eight terms, Dorothy was known for her leadership on natural resources, tax reform, economic development, and other difficult issues during which time she gained recognition for her consensus-building approach. Campaigning by riding her horse across the state, Dorothy was the Democratic nominee for Governor in 1992, losing the race by less than a percentage point. In 1993 she briefly taught at a small rural school next to the Northern Cheyenne Indian Reservation. She was then hired as the Director of the Montana University System Water Center, an education and research arm of Montana State University. From 2000 - 2008 she served as the first Gallatin County Court Administrator with the task of collaboratively redesigning the criminal justice system. She currently serves on One Montana’s Board, is a National Advisor for the American Prairie Foundation, and is on NorthWestern Energy’s Board of Directors. Dorothy was recognized with an Honorary Doctorate from her alma mater, Colorado College, was named Business Woman of the Year by the Bozeman Chamber of Commerce and MSU Alumni Association, and was Montana Business and Professional Women’s Montana Woman of Achievement. Marilyn Wessel was born in Iowa, lived and worked in Los Angeles, California, and Washington, D.C. before moving to Bozeman in 1972. She has an undergraduate degree in journalism from Iowa State University, graduate degree in public administration from Montana State University, certification from the Harvard University Institute for Education Management, and served a senior internship with the U.S. Congress, Montana delegation. In Montana Marilyn has served in a number of professional positions, including part-time editor for the Montana Cooperative Extension Service, News Director for KBMN Radio, Special Assistant to the President and Director of Communications at Montana State University, Director of University Relations at Montana State University and Dean and Director of the Museum of the Rockies at MSU. Marilyn retired from MSU as Dean Emeritus in 2003. Her past Board Service includes Montana State Merit System Council, Montana Ambassadors, Vigilante Theater Company, Montana State Commission on Practice, Museum of the Rockies, Helena Branch of the Ninth District Federal Reserve Bank, Burton K. Wheeler Center for Public Policy, Bozeman Chamber of Commerce, and Friends of KUSM Public Television. Marilyn’s past publications and productions include several articles on communications and public administration issues as well as research, script preparation and presentation of several radio documentaries and several public television programs. She is co-author of one book, 4-H An American Idea: A History of 4-H. Marilyn’s other past volunteer activities and organizations include Business and Professional Women, Women's Political Caucus, League of Women Voters, and numerous political campaigns. She is currently engaged professionally in museum-related consulting and part-time teaching at Montana State University as well as serving on the Editorial Board of the Bozeman Daily Chronicle and a member of Pilgrim Congregational Church and Family Promise. Marilyn and her husband Tom, a retired MSU professor, live in Bozeman. She enjoys time with her children and grandchildren, hiking, golf, Italian studies, cooking, gardening and travel. Jane Jelinski is a Wisconsin native, with a BA from Fontbonne College in St. Louis, MO who taught fifth and seventh grades prior to moving to Bozeman in 1973. A stay-at-home mom with a five year old daughter and an infant son, she was promptly recruited by the Gallatin Women’s Political Caucus to conduct a study of Sex-Role Stereotyping in K Through 6 Reading Text Books in the Bozeman School District. Sociologist Dr. Louise Hale designed the study and did the statistical analysis and Jane read all the texts, entered the data and wrote the report. It was widely disseminated across Montana and received attention of the press. Her next venture into community activism was to lead the successful effort to downzone her neighborhood which was under threat of encroaching business development. Today the neighborhood enjoys the protections of a Historic Preservation District. During this time she earned her MPA from Montana State University. Subsequently Jane founded the Gallatin Advocacy Program for Developmentally Disabled Adults in 1978 and served as its Executive Director until her appointment to the Gallatin County Commission in 1984, a controversial appointment which she chronicled in the Fall issue of the Gallatin History Museum Quarterly. Copies of the issue can be ordered through: http://gallatinhistorymuseum.org/the-museum-bookstore/shop/. Jane was re-elected three times as County Commissioner, serving fourteen years. She was active in the Montana Association of Counties (MACO) and was elected its President in 1994. She was also active in the National Association of Counties, serving on numerous policy committees. In 1998 Jane resigned from the County Commission 6 months before the end of her final term to accept the position of Assistant Director of MACO, from where she lobbied for counties, provided training and research for county officials, and published a monthly newsletter. In 2001 she became Director of the MSU Local Government Center where she continued to provide training and research for county and municipal officials across MT. There she initiated the Montana Mayors Academy in partnership with MMIA. She taught State and Local Government, Montana Politics and Public Administration in the MSU Political Science Department before retiring in 2008. Jane has been married to Jack for 46 years, has two grown children and three grandchildren.

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal

BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category. RESULTS: During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]). CONCLUSIONS: In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland

Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.

IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura

BACKGROUND: ADAMTS13-neutralizing IgG autoantibodies are the major cause of acquired thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To analyze the IgG subclass distribution of anti-ADAMTS13 antibodies and a potential relationship between subclass distribution and disease prognosis. METHODOLOGY: An enzyme-linked immunosorbent assay-based method was used to quantify the relative amounts of IgG subclasses of anti-ADAMTS13 antibodies in acquired TTP plasma. RESULTS: IgG(4) (52/58, 90%) was the most prevalent IgG subclass in patients with acquired TTP, followed by IgG(1) (52%), IgG(2) (50%), and IgG(3) (33%). IgG(4) was found either alone (17/52) or with other IgG subclasses (35/52). IgG(4) was not detected in 10% of the patients. There was an inverse correlation between the frequency and abundance of IgG(4) and IgG(1) antibodies (P < 0.01). Patients with high IgG(4) levels and undetectable IgG(1) are more prone to relapse than patients with low IgG(4) levels and detectable IgG(1). CONCLUSIONS: All IgG subclasses of anti-ADAMTS13 antibodies were detected in patients with acquired TTP, with IgG(4), followed by IgG(1), antibodies dominating the anti-ADAMTS13 immune response. Levels of IgG(4) could be useful for the identification of patients at risk of disease recurrence.

VH1-69 germline encoded antibodies directed towards ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura

BACKGROUND: Autoantibodies directed towards ADAMTS13 are present in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). Analysis of a set of antibodies derived from two patients with acquired TTP revealed frequent use of the VH1-69 heavy chain gene segment for the assembly of anti-ADAMTS13 antibodies. OBJECTIVE: We explored the ability of two VH1-69 germline gene-encoded antibodies to inhibit the von Willebrand factor (VWF)-processing activity of ADAMTS13 under different experimental conditions. Furthermore, the presence of VH1-69 encoded anti-ADAMTS13 antibodies in 40 patients with acquired TTP was monitored using monoclonal antibody G8, which specifically reacts with an idiotype expressed on VH1-69 encoded antibodies. METHODS AND RESULTS: Binding of the two VH1-69 encoded monoclonal antibodies was dependent on the presence of the spacer domain. Both antibodies inhibited ADAMTS13 activity under static conditions, as measured by cleavage of FRETS-VWF73 substrate and cleavage of VWF multimers. The recombinant antibodies were also capable of inhibiting the processing of UL-VWF strings on the surface of endothelial cells. G8-reactive antibodies directed towards ADAMTS13 were present in plasma of all patients containing anti ADAMTS13 antibodies. CONCLUSIONS: These results suggest that VH1-69 derived antibodies directed towards ADAMTS13 develop in the majority of patients with acquired TTP.

Cholesteatoma triggering squamous cell carcinoma: case report and literature review of a rare tumor

BACKGROUND: The aim of this study was to report a case of squamous cell carcinoma of the petrous part of the temporal bone associated with a long history of secondary acquired cholesteatoma in a 71-year-old man. PATIENTS AND METHODS: We present the case of a 71-year-old man diagnosed with secondary acquired cholesteatoma in 1950. Treatments consisted of repetitive surgery owing to several relapses. In 2004, he presented with progressive fetid otorrhea. Clinical and computed tomography findings were indicative for relapsing cholesteatoma and a subtotal petrosectomy was performed. RESULTS: Histologic work-up demonstrated a moderately differentiated squamous cell carcinoma. The staging revealed stadium pT3 cN0 cM0. Postoperative treatment consisted of local radiation therapy with intensity-modulated beam geometry with a total of 64.2 Gy in 30 fractions using a simultaneous integrated boost. CONCLUSION: Middle ear carcinoma can arise from acquired cholesteatoma. The pathogenesis of squamous cell carcinoma associated with cholesteatoma has not been elucidated satisfactorily. Due to the complex anatomic features, intensity-modulated radiation therapy is the technique of choice for postoperative radiotherapy.

JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.