Planning and management to control and eliminate HTLV-1 infection in Iran.

Prevention and treatment of the Human T-cell leukemia virus, type 1 (HTLV-1) which was discovered nearly 40 years ago, still remain challenging. The reported high prevalence of HTLV-1 in some countries around the world triggered an open letter to the World Health Organization (WHO), urging action against HTLV-1 infection in 2018. This highlights the importance of virus elimination strategies to eradicate HTLV-1 infection. In Iran, we have documented our experiences with the virus in order to achieve and promote the possible ways to manage, control, and eliminate HTLV-1. Although there has been considerable progress apropos of HTLV-1, a series of additional challenges need to be tackled to control HTLV-1 infection in Iran.

Accuracy and Precision of the SynchroMed II Pump.

OBJECTIVE: The objective of this study was to evaluate the accuracy and precision of SynchroMed II programmable infusion pumps for delivery of intrathecal baclofen to treat severe spasticity. DESIGN: Retrospective chart review study. SETTING: Urban academic rehabilitation clinic. PATIENTS (OR PARTICIPANTS): Patients with spasticity treated with intrathecal baclofen. METHODS OR INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS): A retrospective chart review of 149 patients inclusive of 755 individual patient encounters more than a 2.5-year span for baclofen pump refills was performed. MAIN OUTCOME MEASUREMENTS: Charts were reviewed to obtain data on the concentration and dose of intrathecal baclofen, aspirated and residual volumes, age of the pump, and reservoir volume of the pump. Flow rate (mL/day) was calculated for each chronological visit. Flow rates from clinical data were used to calculate the accuracy and precision based on the manufacturer's specifications for both the 20 mL and 40 mL pumps. RESULTS: The infused volume accuracy and precision of both the 20 mL pumps and 40 mL pumps remained within manufacturer's specifications while delivering drug at a rate slightly lower than predicted. There were no cases of pump over-infusion. There is a statistically significant decrease in flow rate accuracy over the lifespan of the pump. CONCLUSIONS: SynchroMed II pumps infuse at slightly less than their predicted rate while remaining within the manufacturer's specifications. No pump over-infusions were noted. Pump flow rate declines over time. Further study is warranted to assess the impact of this flow rate decrease on patient treatment and safety.

Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report.

PURPOSE: Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by chronic infection with human T-lymphotropic virus type 1 with diverse clinical features and prognosis. ATL remains a challenging disease as a result of its diverse clinical features, multidrug resistance of malignant cells, frequent large tumor burden, hypercalcemia, and/or frequent opportunistic infection. In 2009, we published a consensus report to define prognostic factors, clinical subclassifications, treatment strategies, and response criteria. The 2009 consensus report has become the standard reference for clinical trials in ATL and a guide for clinical management. Since the last consensus there has been progress in the understanding of the molecular pathophysiology of ATL and risk-adapted treatment approaches. METHODS: Reflecting these advances, ATL researchers and clinicians joined together at the 18th International Conference on Human Retrovirology-Human T-Lymphotropic Virus and Related Retroviruses-in Tokyo, Japan, March, 2017, to review evidence for current clinical practice and to update the consensus with a new focus on the subtype classification of cutaneous ATL, CNS lesions in aggressive ATL, management of elderly or transplantation-ineligible patients, and treatment strategies that incorporate up-front allogeneic hematopoietic stem-cell transplantation and novel agents. RESULTS: As a result of lower-quality clinical evidence, a best practice approach was adopted and consensus statements agreed on by coauthors (> 90% agreement). CONCLUSION: This expert consensus highlights the need for additional clinical trials to develop novel standard therapies for the treatment of ATL.

A survey of anaphylaxis etiology and treatment.

Identifying the causes of anaphylaxis which is an acute, potentially fatal systemic reaction is very important in every community. Treatment strategies and pitfalls should also be determined. We sought to determine the most common triggers of anaphylaxis, clinical manifestations and treatment strategies in Mashhad, northeast of Iran. An observational cross-sectional study was conducted to evaluate all patients with a history of anaphylactic reaction who were referred to University Allergy Clinics between 2006 and 2016 in Mashhad Iran. We used a combination of patient's clinical history and allergy diagnostic testing including radioallergosorbant test and skin prick test in order to determine the etiology of anaphylaxis. We identified 172 anaphylactic reactions in 70 patients. Median age was 15 years with a range from 6 months to 48 years. The triggers included: foods, 61.4%; drugs, 15.7%; hymenoptera venom, 8.6%; idiopathic, 5.7%; immunotherapy, 4.3% and other etiologies: 5.7%. Nuts and seeds were the most important triggers of food induced anaphylaxis, especially in school children, adolescents and young adults, followed by fruits. However, Cow's milk and hen's egg were the main triggers of anaphylaxis in children aged under 2 years. The most common symptoms were cutaneous and cardiovascular. Corticosteroids (94.3%) and/or antihistamines (85.7%) were used most frequently for treatment followed by intravenous fluids (54.3%), whereas epinephrine was only used in 17.1% of the cases. Food related anaphylaxis and other typical triggers of anaphylaxis are age dependent and the risks and triggers change with age. Epinephrine injection should be increased by improving the awareness of physician and medical teams. The study was approved by the Ethics Committee of the Faculty of Medicine of Mashhad University of Medical Sciences (approved number: IR.MUMS.REC.1393.960).

Best Practices for Intrathecal Baclofen Therapy: Troubleshooting.

INTRODUCTION: Troubleshooting helps optimize intrathecal baclofen (ITB) therapy in cases of underdose, overdose, and infection. METHODS: An expert panel of 21 multidisciplinary physicians currently managing >3200 ITB patients was convened, and using standard methodologies for guideline development, created an organized approach to troubleshooting ITB. They conducted a structured literature search that identified 263 peer-reviewed papers, and used results from an online survey of 42 physicians currently managing at least 25 ITB patients each. RESULTS: The panel developed two algorithms. The first was for loss-of-efficacy and applies to patients with previously well-controlled hypertonia on a stable dosing regimen who have increased spasticity Evaluation includes a targeted history (onset, duration, course, exacerbating/relieving factors, medications, recent procedures), physical examination (neuromuscular, vital signs, mental status), radiologic/laboratory testing (catheter imaging, noxious stimuli, infection, rising CK levels), and pump telemetry (pump interrogation, reservoir volume). Rapidly progressing hypertonia with autonomic instability or hypotonia and somnolence require emergent care and perhaps hospitalization. The second algorithm was for emergent care and describes treatment of overdose or withdrawal, which requires immediate care in a monitored setting and restoration of ITB delivery. The previous dosing schedule can be used in withdrawal of short duration; 10-20 mg every six hours can be used in longer-duration withdrawal. Supportive care includes maintenance of airway, respiration, and circulation. Seizure prevention should be considered, along with pump reprogramming or interruption, cerebrospinal fluid drainage, and sequential lumbar punctures/drains. Physostigmine and flumazenil are not usually advised. Superficial infections can be treated with oral antibiotics, and deep infections with broad-spectrum IV antibiotics (e.g., cefazolin, clindamycin, vancomycin). Explantation is often required. A new pump can be implanted in a new site under IV antibiotic coverage. CONCLUSIONS: Orderly troubleshooting helps ensure patient safety.

Trace Elements Status in Sera of Patients with Allergic Asthma.

BACKGROUND: Asthma is a multifactorial disease and its severity varies with the inflammatory grade. There are conflicting reports about the roles of trace elements in asthma. This study examined the effects of zinc (Zn), copper (Cu), and selenium (Se) concentrations in sera of patients with allergic asthma attending Ghaem Hospital, Mashhad, Iran. METHODS: Forty-nine patients, aged 10 to 50 years, with asthma in moderate or severe stages, and 24 healthy controls, were enrolled in this study. After demographic data collection and clinical evaluations, the subjects' serum concentrations of Zn, Cu, and Se were measured via atomic absorbency. RESULTS: Mean serum levels of Zn and Se in patients with allergic asthma were lower than in the healthy control group, but the Cu concentration in sera of patients with allergic asthma was slightly higher than healthy controls. CONCLUSION: Low levels of trace elements, specifically Zn, may have a role in the pathogenesis of allergic asthma; replacement of these elements may be an effective treatment.

The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.

BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4⁺CD25⁺ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4⁺CD25⁺ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

Food-dependent exercise-induced anaphylaxis due to wheat in a young woman.

Food Dependent Exercise-Induced Allergy is a rare condition. However, the occurrence of anaphylaxis is increasing especially in young people. The diagnosis of anaphylaxis is based on clinical criteria and can be supported by laboratory tests such as serum tryptase and positive skin test results for specific IgE to potential triggering allergens. Anaphylaxis prevention needs strict avoidance of confirmed relevant allergen. Food-exercise challenge test may be an acceptable method for diagnosis of Food Dependent Exercise-Induced Allergy and dietary elimination of food is recommended to manage it. In this study, a 32 year-old woman visited the allergy clinic with a history of several episodes of hives since 11 years ago and 3 life-threatening attacks of anaphylaxis during the previous 6 months. The onsets of majority of these attacks were due to physical activity after breakfast. On Blood RAST test, the panel of common food Allergens was used and she had positive test only to wheat flour. On skin prick tests for common food allergens she showed a 6 millimeter wheal with 14 mm flare to Wheat Extract. The rest of allergens were negative.The patient was diagnosed as wheat-dependent exercise-induced, and all foods containing wheat were omitted from her diet. In this report we emphasized on the importance of careful history taking in anaphylaxis diagnosis.

Quality of intrathecal baclofen from different sources.

OBJECTIVE: To compare the quality of intrathecal baclofen obtained from a national compounding pharmacy (AnazaoHealth) with the manufactured product (Lioresal) with regard to accuracy and precision of baclofen concentration, and the content of the baclofen degradation product, 4-(4-chlorophenyl)-2-pyrrolidinone (PYR). DESIGN: Samples of baclofen used for refilling intrathecal pumps were placed in 1.2-mL silicone gasket-sealed cryogenic vials and stored at or lower than -25°C. Each sample was a different lot number (Lioresal) or prescription number (AnazaoHealth). The laboratory was blinded to the source of the solutions. Coupled with electrospray ionization-mass spectrometry analyte confirmation, quantitation of baclofen and PYR in each sample was performed in duplicate by using high-performance liquid chromatography with ultraviolet detection via a photodiode array detector. SETTING: Outpatient clinic. PARTICIPANTS: Patients with intrathecal baclofen pumps. MAIN OUTCOME MEASURES: Accuracy and precision of baclofen concentration, and concentration of PYR. RESULTS: The difference of mean concentrations from expected concentrations of 500 and 2000 µg/mL were significantly greater for samples from AnazaoHealth compared with Lioresal. Values are shown as mean (± standard error), with n the number samples, for AnazaoHealth compared with Lioresal: (537.1 ± 6.7 µg/mL [n = 8] versus 515.6 ± 0.82 µg/mL [n = 5]; P = .034, respectively) and (2211.4 ± 21.6 µg/mL [n = 12] versus 2055.3 ± 8.7 µg/mL [n = 4]; P = .004, respectively). AnazaoHealth samples with expected concentration of 4000 µg/mL were 3987.7 ± 79.9 µg/mL, n = 7. All 9 Lioresal samples were within 5% of the expected concentration. Of 27 AnazaoHealth samples, 22 were more than 5%, and 8 were more than 10% different from the expected concentration. No PYR was detected in any sample from AnazaoHealth. All samples of Lioresal contained PYR, but all solutions contained less PYR than 1% of the baclofen concentration. CONCLUSIONS: Lioresal was more accurate in concentration and more precise among batches than compounded intrathecal baclofen but had higher levels of PYR.

Effect of silymarin in the treatment of allergic rhinitis.

OBJECTIVE: Although the role of oxidative stresses has been confirmed in the pathophysiology of allergic rhinitis and the protective effect of silymarin against oxidative stresses has been proven in different organs, no study has yet been conducted on the impact of silymarin on allergic rhinitis treatment. STUDY DESIGN: A randomized clinical trial study. SETTING: Two tertiary referral centers with otorhinolaryngology-head and neck surgery and allergy and immunology departments. PATIENTS AND METHODS: In a randomized clinical trial, 94 patients with the signs and symptoms of allergic rhinitis and a positive skin prick test were selected and randomly divided into 2 groups. Their signs and symptoms, eosinophil percentage on nasal smear, serum IgE, and interleukin (IL-4, IL-5, interferon-γ) levels were recorded. The study group was treated with silymarin, whereas the control group received placebo, both for 1 month, along with routine antihistamine treatment. At the end of the treatment course, clinical and laboratory findings were statistically analyzed. RESULTS: Sixty patients completed the trial. Based on the Sino-Nasal Outcome Test 20 (SNOT-20), a significant improvement in clinical symptom severity was observed in both groups (9.23 ± 5.14 vs 2.20 ± 2.69; P < .001), which was statistically significantly higher in the study group (P < .001). Posttreatment percentage of nasal eosinophils and cytokine levels showed no significant difference (P > .05). Rise in serum IgE level was seen after treatment with silymarin (P = .003). CONCLUSION: Considering the statistically effective role of silymarin in alleviating the severity of allergic rhinitis symptoms, applying this herbal antioxidant along with other medications may result in better management.

High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey.

BACKGROUND: Mashhad, in the northeast of Iran has been suggested as an endemic area for human T cell lymphotropic virus type I (HTLV-I) infection since 1996. OBJECTIVES: We performed a community-based seroepidemiology study to examine the prevalence and risk factors for HTLV-I infection in the city of Mashhad. STUDY DESIGN: Between May and September 2009, overall 1678 subjects from all the 12 geographical area of Mashhad were selected randomly by multistage cluster sampling for HTLV antibody. The study population included 763 males and 915 females, with the mean age of 29.1 ± 18.5 years. 1654 serum samples were assessed for HTLV antibody using ELISA and reactive samples were confirmed by Western blot and PCR. RESULTS: The overall prevalence of HTLV-I infection in whole population was 2.12% (95% CI, 1.48-2.93) with no significant difference between males and females (p = 0.093) and the prevalence of HTLV-II seropositivity was 0.12% (95% CI, 0.02-0.44). The HTLV-I Infection was associated with age (p<0.001), marital status (p<0.001), education (p = 0.047), and history of blood transfusion (p = 0.009), surgery (p<0.001), traditional cupping (p = 0.002), and hospitalization (p = 0.004). In logistic regression analysis, age was the only variable that had a significant relation with the infection (p = 0.006, OR = 4.33). CONCLUSIONS: Our results demonstrated that Mashhad still remains an endemic area for HTLV-I infection despite routine blood screening. Thus, further strategies are needed for prevention of the virus transmission in whole population.

A review of allergy and allergen specific immunotherapy.

Since 20th century, when allergy was defined, an ongoing attempt for discovering the mechanisms underlying it and its treatment began. Defining allergens as well as cells such as regulatory T-cells and characterizing the antibodies involved in the pathogenesis (including blocking antibodies) have helped very much towards a better understanding of the immunologic process. However, allergen specific immunotherapy (SIT), as a specific curative treatment for allergy also dates back to the beginning of the previous century and has progressed considerably during these years. SIT similar to natural immunomodulation, directs the immune response towards tolerance. New strategies in this field, such as using recombinant allergens, T- and B-cell-epitope-containing peptides, and DNA vaccination have shown promising results. Sublingual immunotherapy, although not yet FDA-approved, as an alternative strategy in SIT has demonstrated efficacy as well as safety. Furthermore, allergen extracts, their standardization and their modification have also been the focus of much research. Undoubtedly, specific immunotherapy is proven to be an efficacious method to treat allergy, so its cost-effectiveness should be estimated in developing countries in order to include it in the country's health priorities. Informing physicians about the new anti-vaccination movement is also crucial.

Evaluation of polymerase chain reaction for diagnosis of "tuberculous pleurisy".

BACKGROUND: Differential diagnosis between tuberculous pleurisy (TBP) and non- tuberculosis pleural effusion represents a critically important clinical problem. In recent years, several noninvasive methods have been found for diagnosis of tuberculous pleurisy. This study aimed to evaluate the value of detection of the genome of Mycobacterium tuberculosis (MTB) by polymerase chain reaction (PCR) method for the diagnosis of tuberculous pleurisy and compare the results with those of conventional methods. MATERIALS AND METHODS: In this cross-sectional study, we studied 62 patients (42 men and 20 women) with pleural effusion in Ghaem Hospital, affiliated to Mashhad University of Medical Sciences from January 2006 to June 2007. RESULTS: A total of 20 patients had tuberculous pleurisy (45.4%), 15 patients had malignant pleural effusion (34%), 3 patients had pleural effusion with various "non-tuberculosis non-malignant" etiologies (6.8%) and 6 patients had transudative pleural effusion (13.6). The sensitivity, specificity, positive predictive value and negative predictive value of PCR in tuberculous pleurisy were 85%, 100%, 100% and 88.8%, respectively. CONCLUSION: The value of PCR test and pleural biopsy was similar in the diagnosis of TBP. However, PCR detected MTB in pleural effusion when conventional pleural biopsy failed to do so.

Effect of a new synbiotic mixture on atopic dermatitis in children: a randomized-controlled trial.

OBJECTIVE: Atopic dermatitis (AD) is the most common chronic relapsing skin disease seen in infancy and childhood. The intestinal microbiota play an important role in immune development and may play a role in the development of allergic disorders. Manipulation of the intestinal microbiota by synbiotics may therefore offer an approach to the prevention or treatment of AD and allergic diseases. We studied the clinical and immunologic effects of a new symbiotic (a mixture of seven probiotic strains of bacteria and Fructooligosaccharide) in infants and children with AD. METHODS: In a randomized, double-blind, placebo-controlled study, 40 infants and children aged 3 months to 6 years with AD received either a synbiotic or placebo for 8 weeks. The Severity Scoring of Atopic Dermatitis (SCORAD) index was recorded at baseline and also at 4 and 8 weeks of treatment. FINDINGS: There was no significant difference between the probiotic and placebo group in baseline characteristics including sex, age, family history, corticosteroid usage and prick testing. Mean age was 23 months. The synbiotic group showed a significantly greater reduction in SCORAD than did the placebo group (P=0.001). No specific effect was demonstrated of the probiotics employed on cytokine profile (P=0.4, P=0.6). Egg white was the most common (45%) allergen followed by peanut and cow's milk. CONCLUSION: This study provides evidence that a mixture of seven strains of probiotics and Fructooligosaccharide can clinically improve the severity of AD in young children. Further studies are needed to investigate the effects on underlying immune responses and the potential long term benefits for patients with AD.

Autoimmune Lymphoproliferative Syndrome (ALPS) in a Boy with Massive Lymphadenopathy.

Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon nonmalignant lymphoproliferative disease which is characterized by chronic, persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly, immune cytopenia , hypergammaglobinemia and increased risk of lymphoma. We report a 2-year old boy with hepatosplenomegaly as first presentation. Petechial and purpuric rashes with massive cervical lymphadenopathies developed 10 months later.In laboratory tests anemia, thrombocytopenia and hypergammaglobinemia were observed. According to flocytometry increased double negative T cells and by apoptosis assay decrease apoptosis of lymphocytes accompanied clinical manifestations, thus diagnosis of ALPS was established. In conclusion; in all patients with massive lymphadenopathy and hepatosplenomegay; especially with cytopenia; ALPS should be considered.

Oral intake of purple passion fruit peel extract reduces pain and stiffness and improves physical function in adult patients with knee osteoarthritis.

Knee osteoarthritis (OA) is a common degenerative joint disorder and a major cause of pain and disability. The hypothesis tested in this study was that the passion fruit peel extract (PFP), a flavonoid-rich dietary supplement, would reduce symptoms due to knee OA. Thirty-three OA patients were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients received either placebo or PFP pills (150 mg, daily) in a double-blinded fashion for 2 months. The OA clinical symptoms were evaluated monthly with Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. In the PFP group, there was a significant improvement in total WOMAC score and WOMAC subscale score of physical function after 30 days and pain after 60 days. At 60 days, reductions of 18.6%, 18%, 19.6%, and 19.2% in pain, stiffness, physical function, and composite WOMAC score, respectively, were self-reported in the PFP group. Whereas, in the placebo group, the self-reported WOMAC scores increased in every category. The results of this study show that PFP substantially alleviated osteoarthritis symptoms. This beneficial effect of PFP may be due to its antioxidant and antiinflammatory properties.

Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).

Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappaB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.