Standardised mortality ratios in people exposed to sulphur mustard during the Iran-Iraq war: a retrospective study with 39-year follow-up.

OBJECTIVES: Sulphur mustard (SM) is a chemical weapon agent that was extensively used by Iraqi troops during the Iran-Iraq war (1980-1988), resulting in exposure among Iranian military personnel and civilians. However, there is limited and conflicting information about the long-term mortality effects of SM exposure. This study aimed to determine the standardised mortality ratios (SMRs) in individuals exposed to SM gas during the Iran-Iraq war. STUDY DESIGN: This was a retrospective follow-up study. METHODS: Data were obtained from the Veterans and Martyr Affair Foundation of Iran (VMAF) regarding all confirmed individuals who were exposed to SM during the Iran-Iraq war (1980-1988) up to 30 March 2019. The mortality rate, cumulative mortality and SMR with 95 % confidence intervals (CIs) were calculated to assess mortality in chemical warfare survivors (CWS), and results were compared with the general Iranian population. Overall survival was analysed using the Kaplan-Meier curve, and the log-rank test was employed to compare survival probability across different categories. RESULTS: Among the 48,067 confirmed CWS, a total of 4358 (9.1 %) individuals had died by the end of the study period (30 March 2019), with a mean age of 55.5 ± 14.4 years at the time of death. Overall, at the 39-year follow-up, the mortality rate due to all causes of death for people who were exposed to SM was lower than the general Iranian population (SMR: 0.70, 95 % CI: 0.68-0.72). However, cause-specific SMR analysis showed that the mortality rate due to liver cancer (SMR: 1.98, 95 % CI: 1.59-2.45), poisonings (SMR: 1.92, 95 % CI: 1.52-2.38), respiratory disorders (SMR: 1.59, 95 % CI: 1.46-1.73) and multiple myeloma (SMR: 1.72, 95 % CI: 1.06-2.62) were approximately twofold higher in CWS than the general population. CONCLUSIONS: This study provides valuable insights into the mortality effects of SM exposure among the Iranian population affected by the Iran-Iraq war. The results emphasise the importance of continued monitoring and support for individuals exposed to SM, particularly in the context of managing and addressing the heightened risks associated with liver cancer, poisonings, respiratory disorders and multiple myeloma. Further research and interventions may be necessary to mitigate these specific health challenges in the affected population.

Ultrafine particle exposure for bicycle commutes in rush and non-rush hour traffic: A repeated measures study in Copenhagen, Denmark.

Ultrafine particles (UFP), harmful to human health, are emitted at high levels from motorized traffic. Bicycle commuting is increasingly encouraged to reduce traffic emissions and increase physical activity, but higher breathing rates increase inhaled UFP concentrations while in traffic. We assessed exposure to UFP while cycling along a fixed 8.5 km inner-city route in Copenhagen, on weekdays over six weeks (from September to October 2020), during morning and afternoon rush-hour, as well as morning non-rush-hour, traffic time periods starting from 07:45, 15:45, and 09:45 h, respectively. Continuous measurements were made (each second) of particle number concentration (PNC) and location. PNC levels were summarized and compared across time periods. We used generalized additive models to adjust for meteorological factors, weekdays and trends. A total of 61 laps were completed, during 28 days (∼20 per time period). Overall mean PNC was 18,149 pt/cm3 (range 256-999,560 pt/cm3) with no significant difference between morning rush-hour (18003 pt/cm3), afternoon rush-hour (17560 pt/cm3) and late morning commute (17560 pt/cm3) [p = 0.85]. There was substantial spatial variation of UFP exposure along the route with highest PNC levels measured at traffic intersections (∼38,000-42000 pt/cm3), multiple lane roads (∼38,000-40000 pt/cm3) and construction sites (∼44,000-51000 pt/cm3), while lowest levels were measured at smaller streets, areas with open built environment (∼12,000 pt/cm3), as well as at a bus-only zone (∼15,000 pt/cm3). UFP exposure in inner-city Copenhagen did not differ substantially when bicycling in either rush-hour or non-rush-hour, or morning or afternoon, traffic time periods. UFP exposure varied substantially spatially, with highest concentrations around intersections, multiple lane roads, and construction sites. This suggests that exposure to UFP is not necessarily reduced by avoiding rush-hours, but by avoiding sources of pollution along the bicycling route.

Exposure to ultrafine particles while walking or bicycling during COVID-19 closures: A repeated measures study in Copenhagen, Denmark.

Ultrafine particles (UFP; particulate matter <0.1 µm diameter) emitted from motorized traffic may be highly detrimental to health. Active mobility (walking, bicycling) is increasingly encouraged as a way to reduce traffic congestion and increase physical activity levels. However, it has raised concerns of increased exposure to UFP, due to increased breathing rates in traffic microenvironments, immediately close to their source. The recent Coronavirus Disease 2019 (COVID-19) societal closures reduced commuting needs, allowing a natural experiment to estimate contributions from motorized traffic to UFP exposure while walking or bicycling. From late-March to mid-July 2020, UFP was repeatedly measured while walking or bicycling, capturing local COVID-19 closure ('Phase 0') and subsequent phased re-opening ('Phase 1', '2', '2.1' & '3'). A DiSCmini continuously measured particle number concentration (PNC) in the walker/bicyclist's breathing zone. PNC while walking or bicycling was compared across phased re-openings, and the effect of ambient temperature, wind speed and direction was determined using regression models. Approximately 40 repeated 20-minute walking and bicycling laps were made over 4 months during societal re-opening phases related to the COVID-19 pandemic (late-March to mid-July 2020) in Copenhagen. Highest median PNC exposure of both walking (13,170 pt/cm3, standard deviation (SD): 3560 pt/cm3) and bicycling (21,477 pt/cm3, SD: 8964) was seen during societal closures (Phase 0) and decreased to 5367 pt/cm3 (SD: 2949) and 8714 pt/cm3 (SD: 4309) in Phase 3 of re-opening. These reductions in PNC were mainly explained by meteorological conditions, with most of the deviation explained by wind speed (14-22%) and temperature (10-13%). Highest PNC was observed along major roads and intersections. In conclusion, we observed decreases in UFP exposure while walking and bicycling during societal re-opening phases related to the COVID-19 pandemic, due largely to meteorological factors (e.g., wind speed and temperature) and seasonal variations in UFP levels.

Quantitative analysis of taste disorder in COVID-19 patients, the hypersensitivity to salty quality.

Recently, many of the studies have illustrated that the new pandemic SARS-CoV-2 can affect Central Nervous System through the olfactory bulb. In addition to investigating anosmia or hyposmia induced by this virus, a quantitative analysis was needed to clarify the taste and smell disorder of the new coronavirus. The four basic taste quality with five concentrations for sweet, sour, bitter, and salty were administered to 75 subjects divided into three groups: COVID-19 patients with taste disorder, COVID-19 patients without taste disorder, and control group. The results indicated the increment of sweet (2.68 ± 0.14), sour (3.34 ± 0.12) and bitter (3.39 ± 0.2) thresholds in COVID-19 patients with taste disorder in comparison with patients without taste disorder that the threshold were: 2 ± 0.16, 2.11 ± 0.2 and 2.55 ± 0.5 for sweet, sour, and bitter respectively. On the other hand, the patients inversely showed a significant decrease in the salty taste threshold (0.51 ± 0.03) compared to COVID-19 positive control groups (1.11 ± 0.11). Additionally, despite taste disorder in almost all of the patients with smell deficiency, only 30% of cases with taste disorder reported smell deficiency. It may be concluded that some of the taste disorders in patients with COVID-19 disorder could be associated with taste receptors dysfunction or the spread of infection to the cranial nerves responsible for the conduction of tastes sensation.

COVID-19 pandemic-induced physical inactivity: the necessity of updating the Global Action Plan on Physical Activity 2018-2030.

To prevent and reduce inactivity, the World Health Organization (WHO) designed a global plan called Global Action Plan on Physical Activity 2018-2030 (GAPPA) in 2017. In this plan and according to the state of physical activity in 2016, actions and goals were set. However, the world is facing a COVID-19 pandemic, which has affected various aspects of lifestyle, including physical activity. Some studies have shown that physical activity reduced during the pandemic. For this reason, the WHO should review the GAPPA and update goals and actions according to the state of physical activity in 2020.

Physical activity during COVID-19 pandemic in the Iranian population: A brief report.

COVID-19 pandemic and restrictive public health measures due to it can have many effects on physical activity. Our study aimed to compare the levels of physical activity levels (expressed as MET-minute/week), among Qom city (Iran) adults in pre and during the COVID-19 pandemic (January 2020 and 20 to 29 May 2020, respectively). 670 adults were included in this study and grouped based on age and gender. The short-form International physical activity questionnaire (IPAQ, SF) was distributed to the participants through an online survey. The Wilcoxon signed-rank test was used for statistical analyses. The present study showed that the level of physical activity decreased significantly during COVID-19 compared to pre-COVID-19 in both sexes and age groups (p < 0.001). Also, this study found that a total of 78% of the participants did not meet the physical activity guidelines during COVID-19 in Iran. Our results indicate the necessity to consider an integrated and comprehensive approach to reduce the inactivity caused by COVID-19.

Improvement of in vitro proliferation of cockerel spermatogonial stem cells using different combinations of growth factors.

1. This study examined whether in vitro proliferation and maintenance of cockerel spermatogonial stem cells (SSCs) could be improved by adding different combinations of growth factors (GFs), including glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF) or leukaemia inhibitory factor (LIF) into the culture medium. 2. The SSCs were isolated from the testes of immature cockerels. For short-term cultures, a medium supplemented with different combinations of GFs for 7 d in 5 replicates was used. The groups were classified as follows: without GF (control group); with GDNF (G group); with GDNF and bFGF (GF group); and with GDNF, bFGF and LIF (GFL group). The number of colonies and cells per colony, as well as the transcript abundance of STRA8 and OCT4 genes, was determined 7 d after the initial culturing. Immunofluorescence staining of SSEA-1, SSEA-3 and VASA protein markers, besides periodic acid-Schiff (PAS) staining, was carried out. 3. The number of colonies and cells per colony increased in the G, GF and GFL groups, compared to the control group (P < 0.01); however, the highest proliferation and colony formation were observed in the GFL group. The positive immunofluorescence staining of SSEA-1, SSEA-3 and VASA protein markers, as well as PAS staining, confirmed the self-renewal and colonisation of cockerel SSCs. The proliferation results were supported by the increased STRA8 and OCT4 transcript abundance in the treated groups (G, GF and GLF), compared to the control group. The SSC proliferation was associated with the higher transcript abundance of STAR8 and OCT4 genes in the GFL group, compared to the G and GF groups (P < 0.01). 4. The results showed that proliferation and colony-forming capacity of cockerel SSCs were positively improved by GDNF, bFGF and LIF. However, the most significant effect was observed when the medium was supplemented with LIF in combination with GDNF and bFGF.

Sensor-less force-reflecting macro-micro telemanipulation systems by piezoelectric actuators.

This paper establishes a novel control strategy for a nonlinear bilateral macro-micro teleoperation system with time delay. Besides position and velocity signals, force signals are additionally utilized in the control scheme. This modification significantly improves the poor transparency during contact with the environment. To eliminate external force measurement, a force estimation algorithm is proposed for the master and slave robots. The closed loop stability of the nonlinear micro-micro teleoperation system with the proposed control scheme is investigated employing the Lyapunov theory. Consequently, the experimental results verify the efficiency of the new control scheme in free motion and during collision between the slave robot and the environment of slave robot with environment, and the efficiency of the force estimation algorithm.

The synergistic effect of beta-boswellic acid and Nurr1 overexpression on dopaminergic programming of antioxidant glutathione peroxidase-1-expressing murine embryonic stem cells.

Parkinson's disease (PD) is a neurodegenerative disorder in which the nigro-striatal dopaminergic (DAergic) neurons have been selectively lost. Due to side effects of levodopa, a dopamine precursor drug, recently cell replacement therapy for PD has been considered. Lack of sufficient amounts of, embryos and ethical problems regarding the use of dopamine-rich embryonic neural cells have limited the application of these cells for PD cell therapy. Therefore, many investigators have focused on using the pluripotent stem cells to generate DAergic neurons. This study is aimed first to establish a mouse embryonic stem (mES) cell line that can stably co-express Nurr1 (Nuclear receptor subfamily 4, group A, member 2) transcription factor in order to efficiently generate DAergic neurons, and glutathione peroxidase-1 (GPX-1) to protect the differentiated DAergic-like cells against oxidative stress. In addition to genetic engineering of ES cells, the effect of Beta-boswellic acid (BBA) on DAergic differentiation course of mES cells was sought in the present study. To that end, the feeder-independent CGR8 mouse embryonic stem cells were transduced by Nurr1- and GPX-1-harboring Lentiviruses and the generated Nurr1/GPX-1-expresssing ES clones were characterized and verified. Gene expression analyses demonstrated that BBA treatment and overexpression of Nurr1 has a synergistic effect on derivation of DAergic neurons from Nurr1/GPX-1-expressing ES cells. The differentiated cells could exclusively synthesize and secrete dopamine in response to stimuli. Overexpression of GPX-1 in genetically engineered Nurr1/GPX-1-ES cells increased the viability of these cells during their differentiation into CNS stem cells. In conclusion, the results demonstrated that Nurr1-overexpressing feeder-independent ES cells like the feeder-dependent ES cells, can be efficiently programmed into functional DAergic neurons and additional treatment of cells by BBA can even augment this efficiency. GPX-1 overexpression in Nurr1/GPX-1-ES cells increases the viability of differentiated CNS stem-like cells. The result of this study may have impact on future stem cell therapy of PD.

Isolation of free-living amoebae from sarein hot springs in ardebil province, iran.

BACKGROUND: Free-living amoebae (FLA) are a group of ubiquitous protozoan, which are distributed in the natural and artificial environment sources. The main aim of the current study was to identify the presence of FLA in the recreational hot springs of Sarein in Ardebil Province of Iran. METHODS: Seven recreational hot springs were selected in Sarein City and 28 water samples (four from each hot spring) were collected using 500 ml sterile plastic bottles during three month. Filtration of water samples was performed, and culture was done in non-nutrient agar medium enriched with Escherichia coli. Identification of the FLA was based on morphological criteria of cysts and trophozoites. Genotype identification of Acanthamoeba positive samples were also performed using sequencing based method. RESULTS: Overall, 12 out of 28 (42.9%) samples were positive for FLA which Acanthamoeba and Vahlkampfiid amoebae were found in one (3.6%) and 11 (39.3%) samples, respectively. Sequence analysis of the single isolate of Acanthamoeba revealed potentially pathogenic T(4) genotype corresponding to A. castellanii. CONCLUSION: Contamination of hot springs to FLA, such as Acanthamoeba T(4) genotype (A. castellanii) and Vahlkampfiid amoebae, could present a sanitary risk for high risk people, and health authorities must be aware of FLA presence.

Relationship between GDx VCC and Stratus OCT in juvenile glaucoma.

PURPOSE: To compare the ability of scanning laser polarimetry (GDx VCC) and optical coherence tomography (OCT) to discriminate eyes with juvenile glaucoma from normal eyes and to assess the relationship between their parameters. METHODS: A total of 24 glaucomatous eyes of 24 patients and 24 normal eyes were enrolled. The age range of the patient was 11-40 years with a mean age of 25.1+/-8.2 years. Control groups consisted 24 eyes of 24 individuals without glaucoma with a mean age of 33.2+/-8.2 years. All subjects underwent a full ophthalmic examination, automated perimetry, GDx VCC, and OCT. Correlation coefficients between the parameters of OCT and GDx VCC were calculated. We calculated the area under the receiver operating characteristic curve (AROC) for the main parameters of GDx VCC and OCT. RESULTS: Statistically significant correlations were observed between GDx VCC and OCT parameters. Pearson coefficients ranged from 0.75 for inferior average to 0.86 for nerve fibre indicator (NFI)/average thickness OCT. The greatest AROC parameter in OCT (inferior average: 0.92) had a lower area than that in GDx VCC (NFI: 0.99). There was a significant statistical significance in all visual field, GDx VCC, and OCT variables between two groups (P<0.05). CONCLUSIONS: Many GDx VCC parameters were significantly correlated with those of the OCT in patients with juvenile glaucoma. Inferior average and NFI had the greatest AROC parameter in OCT and GDx VCC, respectively. NFI had high sensitivity and specificity for the diagnosis of JOAG.

Hydrogen sulfide removal by Thiobacillus thioparus bacteria on seashell bed biofilters.

The aim of this research is to achieve an efficient and cheap methods to remove H2S from the factories emissions. Four serial cylinders are designed, 40 cm in height and 15 cm in diameter each. They are filled with bivalve seashells with 63% porosity which contains Thiobacillus thioparus bacteria to the maximum height of 27.5 cm. By mixing phosphoric acid and sodium sulfide, H2S gas is released and its concentration is measured as mg m(-3) before injecting into the cylinders. A permanent measuring instrument is equipped to control the gas coming out of the cylinders. In order to prevent the outdoor environment from pollution, first the gas is sent through two activated carbon columns and then sent through a ferrous chloride scrubber. Finally it is burnt directly by flames. There were 550 sample readings in 15 weeks. The changes in the discharge of the air which carries the gas are considered between 1-12 L min(-1) and the concentration of the influent pollutant is considered between 1-140 mg m(-3). Also the humidity in the atmosphere is fixed between 77-93% and the optimum temperature required for growing of the microorganisms is retained between 20.5-30 degrees C. After feeding the system for three weeks the efficiency started to increase so that by the end of the final week of this research the efficiency reached to 90% with the discharge of 6 L min(-1) of the carrier gas. The results achieved from this research show that because of not using Filamentous bacteria, clogging did not occur in the biological system in biofilters. The amount of head loss in cylinder was only 2 mm water and during this research, head loss was the same due to unclogging of filter. On the other hand the traditional methods are expensive in terms of using chemicals, carbon recycling and using fuel and etc. Therefore researchers have started new studies in this field. The above mentioned method, according to high efficiency, inexpensiveness and easiness of control and maintenance is considered one of the best methods.

Pharmacokinetics, efficacy, and safety of Iminoral compared with Neoral in healthy volunteers and renal transplant recipients.

UNLABELLED: This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral (reference) in healthy volunteers, as well as safety and efficacy of Iminoral treatment in renal transplant recipients following conversion from Neoral. METHODS: After an overnight fast, 18 healthy volunteers received the assigned treatment (test or reference, 200 mg single dose) in a cross-over fashion with a washout period of 14 days. The blood samples were drawn at various times after drug administration. Cyclosporine blood concentration was measured by high-performance liquid chromatography using an ultraviolet detector. In the second phase of study, stable renal transplant patients who were on Neoral were enrolled in the study in an open-label manner. They were converted from Neoral to Iminoral based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum creatinine, lipid profile, electrolytes, and uric acid were measured before and periodically after conversion for 6 months. RESULTS: The 90% confidence interval of the test/reference ratio was within the acceptable limits of 0.8 to 1.25. Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no significant difference in cyclosporine concentrations and serum creatinines following conversion to Iminoral in renal transplant patients (n=41). There were no reports of major toxicity or of graft rejection and no need for dose adjustment related to Iminoral. CONCLUSIONS: Single doses of Neoral and Iminoral are bioequivalent in healthy subjects. Renal transplant recipients maintained on Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion ratio.

Characterization of a thermal power plant air heater washing waste: a case study from Iran.

In Iran most of the electricity is generated by thermal power plants. As a result of fuel oil burning in winter time, the air heaters of the boilers have to be washed and cleaned frequently. The wastewater originating from air heater washing is then treated in an effluent treatment plant by chemical precipitation followed by dewatering of the sludge produced. The resulting waste is classified as specific industrial waste that should be characterized in detail under the Waste Management Act of Iran. The quantity of this waste produced in the studied power plant is about 20 tonnes year(-1). In the present investigation, the first to be carried out in Iran, seven composite samples of dewatered sludge from air heater washing wastewater treatment were subjected to investigation of the physical properties, chemical composition and leaching properties. The most likely pollutants that were of concern in this study were heavy and other hazardous metals (Cd, Co, Cr, Mn, Ni, Pb, Zn and V). The results revealed that mean pH, wet and dry density and moisture content of the waste were 6.31, 1532 kg m(-30, 1879 kg m(-3) and 15.35%, respectively. Magnetite, SiO2, P2O5, CaO, Al2O3 and MgO were the main constituents of the waste with a weight percentage order of 68.88, 5.91, 3.39, 2.64, 2.59 and 1.76%, respectively. The toxicity characteristic leaching procedure test results for some heavy and other hazardous metals showed that mean elemental concentrations of Cd, Co, Cr, Mn, Ni, Pb, V and Zn in leachate were 0.06, 1.55, 5.49, 36.32, 209.10, 0.58, 314.06 and 24.84 mg L(-1), respectively. According to the Waste Management Act of Iran this waste should be classified as hazardous and should be disposed of in accordance with hazardous waste disposal regulations.

Non-affective Acute Remitting Psychosis: a preliminary report from Iran.

OBJECTIVE: To investigate the concept of 'Non-affective Acute Remitting Psychosis' (NARP) in a group of patients with first episode psychosis in Iran. METHOD: This is a 24-month follow-up study of 54 patients with first-episode psychosis admitted consecutively to a psychiatric hospital in Tehran, Iran. At the end of follow-up, consensus judgments were made on fulfillment of the NARP criteria as well as illness course and treatment. NARP was defined as a psychotic illness with acute onset (developed within 1 week), short duration (remission within 6 months), and the absence of prominent mood symptoms. RESULTS: Of 49 patients who completed the follow-up, 15 (30.6%) had NARP, accounting for 60% of non-affective psychoses. Ten patients with NARP remained relapse free, four had a very short-lived relapse, and only one developed a chronic illness. Throughout the follow-up, patients with NARP received fewer months of treatment than did patients with other non-affective psychoses. CONCLUSION: The high proportion of NARP among patients with first episode psychosis, and the favorable course is in keeping with previous studies in developing countries.

Ascorbate reduces morphine-induced extracellular DOPAC level in the nucleus accumbens: A microdialysis study in rats.

Most drugs of abuse increase dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the shell of the nucleus accumbens. The effects of ascorbate, which is known to modulate dopamine neurotransmission, on the extracellular level of DOPAC in the nucleus accumbens of naive rats and of rats treated acutely with morphine were studied by using in vivo microdialysis and high performance liquid chromatography with electrochemical detection (HPLC-ECD). Acute morphine (20 mg/kg ip) treatment increased the level of DOPAC in the nucleus accumbens to approximately 170% of basal level. Acute treatment with ascorbate (500 mg/kg ip) alone did not alter nucleus accumbens' DOPAC level, but pretreatment with ascorbate (500 mg/kg ip) 30 min before morphine administration attenuated the effects of acute morphine on the level of DOPAC. These results suggest that ascorbate modulates the mesolimbic dopaminergic pathway.

Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.

BACKGROUND: Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder. METHODS: Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6. RESULTS: Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant. CONCLUSION: In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.

Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial.

OBJECTIVE: Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. METHODS: Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. RESULTS: The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant. CONCLUSION: The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial.