Intrathecal morphine pump for neuropathic cancer pain: a case report

The WHO ladder has been the most widely used approach for management of Cancer Pain. However, oral medications alone may be inadequate, particularly in difficult to treat cancer pain syndromes. Neuropathic pain is one of these refractory syndromes. The role of opioids has always been controversial in pain of neuropathic origin. We report a case of a 61 year old female patient with endometrial carcinoma suffering from severe neuropathic pain in her left lower limb. The pain was refractory to highest tolerable doses of oral morphine and neuromodulator drugs, viz. gabapentin and pregabalin. We managed the patient successfully with intrathecal morphine pump reducing the total morphine dose and improving patient comfort and satisfaction. Intrathecal delivery of Morphine ensured better efficacy with fewer side effects.     

Project-Based Housing First for Chronically Homeless Individuals With Alcohol Problems: Within-Subjects Analyses of 2-Year Alcohol Trajectories

Objectives. Two-year alcohol use trajectories were documented among residents in a project-based Housing First program. Project-based Housing First provides immediate, low-barrier, nonabstinence-based, permanent supportive housing to chronically homeless individuals within a single housing project. The study aim was to address concerns that nonabstinence-based housing may enable alcohol use.Methods. A 2-year, within-subjects analysis was conducted among 95 chronically homeless individuals with alcohol problems who were allocated to project-based Housing First. Alcohol variables were assessed through self-report. Data on intervention exposure were extracted from agency records.Results. Multilevel growth models indicated significant within-subjects decreases across alcohol use outcomes over the study period. Intervention exposure, represented by months spent in housing, consistently predicted additional decreases in alcohol use outcomes.Conclusions. Findings did not support the enabling hypothesis. Although the project-based Housing First program did not require abstinence or treatment attendance, participants decreased their alcohol use and alcohol-related problems as a function of time and intervention exposure.A review of 29 studies conducted worldwide estimated an alcohol dependence prevalence of 37.9% among homeless populations.1 Among chronically homeless individuals (i.e., people with long-term, often-repeated episodes of homelessness2), the prevalence of alcohol dependence is even higher.3 Alcohol dependence is associated with greater levels of alcohol problems, resulting from acute intoxication or long-term alcohol use, as well as increased risk for alcohol-related deaths.4–7Unfortunately, traditional housing infrastructures designed to serve chronically homeless individuals with alcohol problems often fail to engage residents and comprehensively address their complex needs.8,9 One reason for this failure might be perceived barriers to housing imposed by housing agencies, such as requiring psychiatric or substance abuse treatment attendance or abstinence from substance use.10 Policymakers have therefore called for the development of low-barrier housing programs that might more effectively engage these individuals, house them, and attend to their needs.11,12Housing agencies have begun to respond to this call by designing project-based Housing First approaches to fit the specific needs of chronically homeless individuals with alcohol problems.13 As in other Housing First approaches (e.g., scattered-site Housing First), project-based Housing First for this population entails the provision of low-barrier, nonabstinence-based (i.e., not requiring abstinence from substance use), immediate, and permanent housing.14,15 Specific to the project-based Housing First model, however, individuals are offered units within a single housing project, where they can elect to receive on-site case management and other supportive services. Although project-based Housing First programs are receiving increased interest in the supportive housing field,16 only a couple of studies to date have examined their effectiveness in this population.13,17 These studies have shown that project-based Housing First programs are associated with increased housing stability, reduced use of publicly funded services and associated costs, and short-term reductions in typical daily alcohol use.13,17Despite encouraging initial findings for the project-based Housing First approach,13 abstinence-based programs are the mainstay of housing models in the United States.18 Alcohol abstinence and abstinence-based treatment requirements are typical across a wide range of housing models (e.g., emergency shelters, transitional housing, halfway houses, permanent supportive housing).19 Even as Housing First models are being recommended as evidence-based best practice12 and are receiving more attention in the press,20,21 debate continues about whether nonabstinence-based housing approaches, such as project-based Housing First, are appropriate for chronically homeless individuals with alcohol problems.22The argument for abstinence-based approaches is typically derived from the disease model of alcohol use disorder etiology, which conceptualizes alcohol dependence as a “chronic, relapsing brain disease.”23,24 Proponents of the disease model posit that alcohol dependence should be treated through interventions designed to help people achieve and maintain abstinence.24 The corollary is that by not prohibiting alcohol use and by supporting clients’ choices about their drinking goals, nonabstinence-based approaches may “enable” or facilitate continued, harmful drinking.25 Despite this widespread belief, there is little empirical data to support it. Recent studies have shown that abstinence-based housing is not necessarily more effective than Housing First approaches26,27 and have indicated that clients and providers prefer the autonomy and sense of stability of Housing First over traditional housing models.28,29The study aim was to address concerns about the appropriateness of project-based Housing First designed for chronically homeless individuals with alcohol problems. Specifically, we tested the enabling hypothesis,25,30 which posits that the provision of nonabstinence-based Housing First would result in stable or increasing levels of alcohol use and alcohol-related problems. We predicted that the enabling hypothesis would not be confirmed and that participants in project-based Housing First would, on the contrary, show significant, within-subjects decreases in alcohol use and alcohol-related problems over a 2-year follow-up.     

Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential

Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity.

Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF).

Materials and methods Antimutagenic potential of AMF (25, 50 and 75?μg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250?mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC–MS.

Results AMF (75?μg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250?mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC–MS.

Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential.     

Orbital medulloepithelioma in an adult patient: Radiation-induced second neoplasia?

Second cancers in survivors of hereditary retinoblastoma occur much more commonly than in the general population. This can be attributed both to the germline mutation of the RB gene and chemoradiation used for treatment of this paediatric cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen largely in the paediatric population and rarely reported in adults. Though the incidence of second malignancies is common in retinoblastoma, medulloepithelioma as a second malignancy in retinoblastoma survivors is rare, with only one case reported so far. Herein, we present a case of a 29-year-old patient presenting with medulloepithelioma of the right orbit, arising in the radiation field of previously treated retinoblastoma. This case was also peculiar in that though the origin of tumor was in the eyeball it had a very aggressive clinical course.     

Cancer pain management: basic information for the young pain physicians

Cancer pain is multifactorial and complex. The impact of cancer pain is devastating, with increased morbidity and poor quality of life, if not treated adequately. Cancer pain management is a challenging task both due to disease process as well as a consequence of treatment-related side-effects. Optimization of analgesia with oral opioids, adjuvant analgesics, and advanced pain management techniques is the key to success for cancer pain. Early access of oral opioid and interventional pain management techniques can overcome the barriers of cancer pain, with improved quality of life. With timely and proper anticancer therapy, opioids, nerve blocks, and other non-invasive techniques like psychosocial care, satisfactory pain relief can be achieved in most of the patients. Although the WHO Analgesic Ladder is effective for more than 80% cancer pain, addition of appropriate adjuvant drugs along with early intervention is needed for improved Quality of Life. Effective cancer pain treatment requires a holistic approach with timely assessment, measurement of pain, pathophysiology involved in causing particular type of pain, and understanding of drugs to relieve pain with timely inclusion of intervention. Careful evaluation of psychosocial and mental components with good communication is necessary. Barriers to cancer pain management should be overcome with an interdisciplinary approach aiming to provide adequate analgesia with minimal side-effects. Management of cancer pain should comprise not only a physical component but also psychosocial and mental components and social need of the patient. With risk-benefit analysis, interventional techniques should be included in an early stage of pain treatment. This article summarizes the need for early and effective pain management strategies, awareness regarding pain control, and barriers of cancer pain.     

A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy

Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital tissues associated with elevated serum levels of TSH receptor (TSHR) autoantibodies. Because previous studies have demonstrated evidence of adipogenesis within the GO orbit, we sought to determine whether M22, a human monoclonal antibody directed against TSHR, enhances adipogenesis in orbital fibroblasts from patients with GO and, if so, to identify signaling mechanisms involved. GO orbital fibroblast cultures (n=10) were treated for 10 days with bovine TSH (1 or 10.0?U/l) or M22 (1 or 10?ng/ml) in serum-free adipocyte differentiation medium. Some cultures also received a phosphoinositide 3-kinase (PI3K) inhibitor or an inhibitor of cAMP production. In other experiments, confluent cultures (n=8) were treated for between 1 and 30 min with TSH (0.1-10.0?U/l) or M22 (0.1-100?ng/ml) with measurement of cAMP production or levels of phosphorylated AKT (pAKT). We found levels of adiponectin, leptin, and TSHR mRNA to be increased in GO cultures treated for 10 days with either M22 (2.6 mean fold ± 0.7; P=0.03) or TSH (13.2 ± 5.8-fold, P=0.048). In other studies, M22 and TSH stimulated cAMP production and pAKT levels in GO cells. Inhibition of PI3K activity during 10 days in culture decreased the levels of M22-stimulated mRNA encoding adiponectin (67 ± 12%; P=0.021), as well as adiponectin and CCAAT/enhancer-binding protein α protein levels. In conclusion, M22 is a pro-adipogenic factor in GO orbital preadipocytes. This antibody appears to act via the PI3K signaling cascade, suggesting that inhibition of PI3K signaling may represent a potential novel therapeutic approach in GO.     

Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients

The ubiquitin-proteasome pathway regulates bone formation through osteoblast differentiation. We analyzed variation alkaline phosphatase (ALP) during carfilzomib treatment. Data from 38 patients enrolled in the PX-171-003 and 29 patients in PX-171-004 studies, for patients with relapsed/refractory myeloma, were analyzed. All patients received 20 mg/m(2) of carfilzomib on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Sixty-seven patients from ALP data were evaluable. In PX-171-003, the ORR (>PR) was 18% and the clinical benefit response (CBR; >MR) was 26%, while in PX-171-004, the ORR was 35.5% overall and 57% in bortezomib-naive patients. ALP increment from baseline was statistically different in patients who achieved ≥ VGPR compared with all others on Days 1 (P = 0.0049) and 8 (P = 0.006) of Cycle 2. In patients achieving a VGPR or better, ALP increased more than 15 units per liter at Cycle 2 Day 1 over baseline. An ALP increase over the same period of time was seen in 26%, 13% and 11% of patients achieving PR, MR, and SD, respectively. This retrospective analysis of patients with relapsed or refractory myeloma treated with single-agent carfilzomib indicates that early elevation in ALP is associated with subsequent myeloma response.