Safety and tolerability of velafermin (CG53135-05) in patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplant

Goals of work The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy. Materials and methods This study was a single-center, open-label, single-dose escalation, phase I trial in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSCT). Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min. Clinical safety variables were assessed and OM status scored daily for 30 days using the World Health Organization (WHO) grading scale. Main results Thirty patients were treated with velafermin at doses of 0.03 (n = 10), 0.1 (n = 10), 0.2 (n = 8), or 0.33 mg/kg (n = 2). Patients were diagnosed with multiple myeloma (n = 16), non-Hodgkin’s lymphoma (n = 12), acute myelogenous leukemia (n = 1), or desmoplasmic round cell tumor (n = 1). Velafermin was well tolerated at doses up to 0.2 mg/kg. There were no drug-related serious adverse events. No patient discontinued because of adverse events; however, two patients administered 0.33 mg/kg developed adverse reactions immediately after infusion of the study drug. No other patients were treated at this dose level. The most frequent (>35% of patients) treatment-emergent adverse events were diarrhea, fatigue, pyrexia, vomiting, and nausea. Most adverse events were mild or moderate and resolved the same day without sequelae. Eight (27%) patients developed WHO grade 3 or 4 OM during the study; seven of these patients received high-dose melphalan as a conditioning regimen. Conclusion Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg.     

An epidemiological survey of psychiatric disorders in Iran

Background

The nation-wide epidemiological survey of psychiatric disorders in term of lifetime prevalence is not adequately known in Iran. The prevalence of lifetime psychiatric disorders was estimated among the population of aged 18 and over on gender, age group, educational level, occupational status, marital status, and residential area.

Methods

The subjects were 25,180 individuals selected through a clustered random sampling method. The psychiatric disorders were diagnosed on the bases of Diagnostic and Statistical Manual of Mental Disorders-IV criteria. It is the first study in which the structured psychiatric interview administered to a representative sample of the Iranian population age 18 and over by the 250 trained clinical psychologist interviewers. The data was entered through EPI-Info software twice in an attempt to prevent any errors and SPSS-11 statistical software was also used for analyses. The odds ratios and their confidence intervals estimated by using logistic regression.

Results and Discussion

The prevalence of psychiatric disorders was 10.81%. It was more common among females than males (14.34% vs. 7.34%, P < 0.001). The prevalence of anxiety and mood disorders were 8.35% and 4.29% respectively. The prevalence of psychotic disorders was 0.89%; neuro-cognitive disorders, 2.78% and dissociative disorders, 0.77%. Among mood disorders, major depressive disorder (2.98%) and among anxiety disorders, phobic disorder (2.05%) had the higher prevalence. The prevalence of psychiatric disorders among divorced and separated 22.31%; residents of urban areas 11.77%; illiterates 13.80%; householders 15.48%; unemployed 12.33% that were more than other groups.

Conclusion

The mental health pattern in Iran is similar to the western countries, but it seems that the prevalence of psychiatric disorders in Iran may be lower than these countries.It is estimated that at least about 7 millions of Iranian population suffer from one or more of the psychiatric disorders. It shows the importance of the role of the psychiatric disorders in providing preventive and management programs in Iran.

     

Unihemispheric concurrent dual‐site cathodal transcranial direct current stimulation: the effects on corticospinal excitability

We aimed to assess the effects of concurrent cathodal transcranial direct current stimulation (c‐tDCS) of two targets in a hemisphere, termed unihemispheric concurrent dual‐site cathodal tDCS (c‐tDCS_UHCDS), on the size of M1 corticospinal excitability and its lasting effect. Secondary aims were to identify the mechanisms behind the efficacy of c‐tDCS_UHCDS and to evaluate the side effects of this new technique. Twelve healthy volunteers received 20 min c‐tDCS under five conditions in a random order: M1 c‐tDCS, c‐tDCS_UHCDS of M1–dorsolateral prefrontal cortex (DLPFC), M1–primary sensory cortex (S1), M1–primary visual cortex (V1) and sham. The M1 corticospinal excitability of the first dorsal interossei muscle was assessed before, immediately after, and 30 min, 60 min and 24 h after the interventions. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were also assessed, using a paired‐pulse paradigm. Compared to conventional M1 c‐tDCS, corticospinal excitability significantly increased following c‐tDCS_UHCDS of M1‐DLPFC and M1‐V1 for up to 24 h (P = 0.001). Significant increases in ICF were observed following c‐tDCS_UHCDS of M1‐DLPFC (P = 0.005) and M1‐V1 (P = 0.002). Compared to baseline values, ICF and SICI increased significantly at T₆₀ (P < 0.001) and T_24 h (P < 0.001) following the concurrent c‐tDCS of M1 and V1. Sham c‐tDCS_UHCDS did not induce any significant alteration. The corticospinal excitability increase was mainly accompanied by ICF increase, which indirectly indicates the activity of glutamergic mechanisms. The findings may help us to more fully understand the brain function and develop future motor learning studies. No significant excitability change induced by sham c‐tDCS_UHCDS suggests that there is no placebo effect associated with this new tDCS technique.     

Screening for generalized anxiety disorder symptoms in the wake of terrorist attacks: A study in primary care

Little is known about the mental health impact of terrorism beyond posttraumatic stress disorder (PTSD) and depression. The associations between exposure to the September 11, 2001 (9/11) attacks in New York City and generalized anxiety disorder (GAD) symptoms were examined in a sample of 929 primary care patients. After controlling for PTSD, depression, panic and substance use disorders, and pre-9/11 trauma, patients who screened positive (vs. negative) for GAD symptoms were roughly twice as likely to report having a loved one at the 9/11 disaster site, twice as likely to know someone who was killed by the attacks, and twice as likely to know someone who was involved with the rescue/recovery efforts after the disaster. Implications for treatment and future research are discussed.     

HLA Class II (DRB,DQA1 and DQB1) Allele and Haplotype Frequencies in the Patients with Pemphigus Vulgaris

Introduction  Pemphigus vulgaris (PV), an autoimmune disease affecting the skin and mucous membranes, is associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. Materials and Methods  In order to evaluate the association of HLA-DR and DQ alleles and haplotypes in Iranian non-Jewish patients with PV, 52 patients with PV and 180 normal subjects as control group were investigated in this study. Results and Discussion  HLA-DRB1*04, -DRB1*1401, -DRB4, -DQA1*0104, -DQA1*03011, -DQB1*0302, and -DQB1*0502 alleles have been significantly increased in our patients group. Moreover, the haplotypes HLA-DRB1*04/-DQA1*03011/-DQB1*0302 and HLA-DRB1*1401/-DQA1*0104/-DQB1*0502 increased significantly in our patients. In contrast, the following alleles decreased significantly in our patients: HLA-DRB1*15, -DRB1*0301, -DRB1*07, -DRB1*11, -DRB5, -DQA1*0101, -DQA1*0103, -DQA1*201, -DQA1*05, -DQB1*0201, -DQB1*0301, -DQB1*06011, and -DQB1*0602. In addition, HLA-DRB1*15/-DQA1*0103/-DQB1*06011, HLA-DRB1*0301/-DQA1*05011/-DQB1*0201, HLA-DRB1*07/-DQA1*0201/-DQB1*0201, and HLA-DRB1*11/-DQA1*05/-DQB1*03011 decreased significantly in our patients. Genetic factors are involved in the occurrence of PV; HLA-DRB1*04 and -DRB1*1401 alleles and the related haplotypes are suggestive to be two major PV susceptibility factors in our population study.     

Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan

Objective  Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples. Methods  Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women. Results  The total daily PCB intake [ng/day, geometric mean (geometric standard deviation)] decreased significantly from 523 (2.5) in 1980 to 63 (3.2) in 2003. The serum total PCB level (ng/g lipid) in women <40 years of age decreased significantly from 185 (1.8) in 1980 to 68 (1.8) in 2003. In contrast, the level in women >50 years of age increased significantly from 125 (1.7) in 1980 to 242 (1.7) in 2003. Specifically, the serum concentrations of hexa (#138, #146, #153, #156, #163, and #164) and hepta (#170, #180, #182, and #187) congeners increased significantly. A comparison of the serum PCB levels of women born from 1940 to 1953 revealed that their serum total PCB level was significantly higher in the 2003 survey [242 (1.7), n = 9] than in the 1995 [128 (2.0), n = 17] surveys. This increase in the total PCB level was attributable to increases in the hepta congener groups. Conclusion  Present results suggest a decreased rate of elimination of hepta congeners with aging in females, rather than a birth-generation phenomenon.     

Association of HLA class II allele and haplotype frequencies with chronic myelogenous leukemia and age-at-onset of the disease

Chronic myelogenous leukemia (CML) is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. To clarify the association between HLA class II allele and haplotype frequencies in CML, 50 patients referred to Hematology Oncology and Bone Marrow Transplantation (BMT) center, Shariaty Hospital, Tehran, Iran, were randomly selected and compared with a group of 80 unrelated healthy blood donor subjects. HLA class II alleles were determined by PCR-SSP method. The results showed that the frequencies of DQB1*03011 (P=0.01) and DQA1*0505 (P=0.05) were higher, while that of DQB1*03032 (P=0.04) was lower in patients than in the controls. Regarding age-at-onset, the frequency of HLA-DRB1*07 (P=0.03) and -DQA1*0201 (P=0.03) alleles were higher in patients younger than 35 years. The most frequent haplotypes in our CML patients were HLA-DRB1*11/-DQB1*03011/-DQA1*0505 (P=0.01) and HLA-DRB1*04/-DQB1*0302/-DQA1*03011 (P=0.02). In conclusion, it is suggested that positive and negative association in certain HLA alleles and haplotypes exist in Iranian patients with CML.     

Etiology, pathogenesis, and management of acute intraocular lens opacification: a systematic review

Millions of cataract surgeries with intraocular lens (IOL) implantation are performed worldwide. Although cataract surgery brings many benefits to the patients, the risk of various complications is still a concern. One of the infrequent adverse events but potentially affecting on patients’ visual acuity and contrast sensitivity is losing the transparency of IOL. IOL opacification may lead to IOL removal or exchange, which is unpleasant to both the patient and the surgeon. Several reports of acute IOL clouding are available in the literature describing various etiologies of this phenomenon, however, the exact mechanism remained unclear in some cases. Herein, we aimed to review the causes and outcomes of intraoperative and early postoperative IOL opacification.