Characterization of 11 New Cases of Leukocyte Adhesion Deficiency Type 1 with Seven Novel Mutations in the ITGB2 Gene

Background

Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the β2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease.

Methods

In order to investigate clinical and molecular manifestations of new LAD I cases, 11 patients diagnosed in one center during 7 years were studied. Patients were screened for the ITGB2 gene mutations, using polymerase chain reaction, followed by single-strand conformation polymorphism and sequencing.

Results

The most common first presenting feature of the patients was omphalitis. The mean age of cord separation was 19.9?±?1 days. The most common clinical manifestations of the patients during the follow-up period included omphalitis, skin ulcers with poor healing, sepsis, and otitis media. During the follow-up, eight patients died. Eight homozygous changes, including seven novel mutations, were detected: two splicing (IVS4?6C>A, IVS7+1G>A), three missense (Asp128Tyr, Ala239Thr, and Gly716Ala), and three frameshift deletions (Asn282fsX41, Tyr382fsX9, and Lys636fsX22).

Conclusion

Our results indicate that different mutations underlie the development of LAD I. Definitive molecular diagnosis is valuable for genetic counseling and prenatal diagnosis. Regarding clinical presentations, it seems that omphalitis is the most consistent finding seen in LAD I infants.     

Validating the Self-assessed Wisdom Scale (SAWS) in an Iranian Sample: Psychometric and Developmental Findings

Journal of Cross-Cultural Gerontology - This study aimed to investigate the validity and factor structure of the Self-Assessed Wisdom Scale (SAWS; Webster in J Adult Dev 10:13–22, 2003) in an...     

N-acetyl-cysteine in the prevention of vascular restenosis after percutaneous balloon angioplasty

BACKGROUND: Vascular inflammation generating oxidized metabolites at the site of balloon angioplasty is believed to play a major role in the process of vessel restenosis. Glutathione, the most potent endogenous antioxidant, may have protective effects after angioplasty by suppressing local inflammatory response. The aim of the study was to test the hypothesis that oral administration of N-acetyl-cysteine (NAC, a precursor of glutathione) reduces restenosis in an animal model of vascular injury. METHODS: In New Zealand white rabbits, an atherosclerotic lesion was introduced to both iliac arteries by air denudation of the endothelium while feeding the animals a high-cholesterol diet. After 4 weeks, all animals underwent balloon angioplasty of the endothelial injury site and half of the group was started on 150 mg/kg NAC per day. Quantitative angiography was performed prior to the angioplasty and at the final procedure 3 weeks later. Glutathione levels were determined in all animals at the beginning and the end of the study. RESULTS: Although not statistically significant, plasma glutathione level increased in the NAC group from 32.4+/-4.4 to 39.7+/-11.6 micromol/l, while it decreased from 30.6+/-13.4 to 28.3+/-11.5 micromol/l in the control group. During the study period, 6 vessels occluded leaving 14 vessels for analysis. Quantitative angiographic analyses prior to angioplasty and at follow-up showed no significant difference with respect to stenosis progression between the groups. Measurement of neointima formation by histology showed also no significant difference between the groups (0.175+/-0.040 mm(2) vs. 0.123+/-0.075 mm(2)), neither did intimal macrophage count as a marker for local inflammatory response. CONCLUSIONS: Despite an increase in plasma glutathione level in the NAC-treated group, there was no reduction in lesion progression after balloon angioplasty. Therefore, NAC does not seem to prevent restenosis after vascular intervention in this animal model.     

Evidence-Based Framework to Manage Cyanobacteria and Cyanotoxins in Water and Sludge from Drinking Water Treatment Plants

Freshwater bodies and, consequently, drinking water treatment plants (DWTPs) sources are increasingly facing toxic cyanobacterial blooms. Even though conventional treatment processes including coagulation, flocculation, sedimentation, and filtration can control cyanobacteria and cell-bound cyanotoxins, these processes may encounter challenges such as inefficient removal of dissolved metabolites and cyanobacterial cell breakthrough. Furthermore, conventional treatment processes may lead to the accumulation of cyanobacteria cells and cyanotoxins in sludge. Pre-oxidation can enhance coagulation efficiency as it provides the first barrier against cyanobacteria and cyanotoxins and it decreases cell accumulation in DWTP sludge. This critical review aims to: (i) evaluate the state of the science of cyanobacteria and cyanotoxin management throughout DWTPs, as well as their associated sludge, and (ii) develop a decision framework to manage cyanobacteria and cyanotoxins in DWTPs and sludge. The review identified that lab-cultured-based pre-oxidation studies may not represent the real bloom pre-oxidation efficacy. Moreover, the application of a common exposure unit CT (residual concentration × contact time) provides a proper understanding of cyanobacteria pre-oxidation efficiency. Recently, reported challenges on cyanobacterial survival and growth in sludge alongside the cell lysis and cyanotoxin release raised health and technical concerns with regards to sludge storage and sludge supernatant recycling to the head of DWTPs. According to the review, oxidation has not been identified as a feasible option to handle cyanobacterial-laden sludge due to low cell and cyanotoxin removal efficacy. Based on the reviewed literature, a decision framework is proposed to manage cyanobacteria and cyanotoxins and their associated sludge in DWTPs.     

Cardiac and Renal Malformations in a Patient with Sepsis and Severe Congenital Neutropenia

Background

G6PC3 deficiency is a new neutropenic syndrome, which is characterized by severe persistent neutropenia, early onset infections and additional organ involvement, especially cardiac and urogenital malformations.

Case Presentation

In this report, we present the clinical details of a recently known case of severe congenital neutropenia (SCN) with G6PC3 mutation, who experienced the first episode of infections at birth. Repeated absolute neutrophil count of less than 500/µl was detected during work-up of sepsis in the first month of life. SCN was diagnosed and granulocyte colony-stimulating factor (GCSF) administration initiated. Bone marrow examination revealed maturation arrest in myeloid series at promyelocyte-myelocyte stage. Diarrhea, bronchiolitis, and urinary tract infection were other infectious complications, while hydronephrosis, atrial septal defect, and patent ductus arteriosus were other manifestations.

Conclusion

Prompt and accurate diagnosis of neutropenic patients and appropriate treatment can prevent further complications and improve the quality of life of the affected patients.     

A Comparison of Buccal Midazolam and Intravenous Diazepam for the Acute Treatment of Seizures in Children

Objective

The purpose of the present study is to compare efficacy and safety of buccal midazolam with intravenous diazepam in control of seizures in Iranian children.

Methods

This is a randomized clinical trial. 92 patients with acute seizures, ranging from 6 months to 14 years were randomly assigned to receive either buccal midazolam (32 cases) or intravenous diazepam (60 cases) at the emergency department of a children''s hospital. The primary outcome of this study was cessation of visible seizure activity within 5 minutes from administration of the first dosage. The second dosage was used in case the seizure remained uncontrolled 5 minutes after the first one.

Findings

In the midazolam group, 22 (68.8%) patients were relieved from seizures in 10 minutes. Meanwhile, diazepam controlled the episodes of 42 (70%) patients within 10 minutes. The difference was, however, not statistically significant (P=0.9). The mean time required to control the convulsive episodes after administration of medications was not statistically significant (P=0.09). No significant side effects were observed in either group. Nevertheless, the risk of respiratory failure in intravenous diazepam is greater than in buccal midazolam.

Conclusion

Buccal midazolam is as effective as and safer than intravenous diazepam in control of seizures.     

A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia

Rationale

Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.

Objectives

We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia.

Methods

In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups.

Results

By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P?<?0.001) as well as the PANSS total and general psychopathology subscale scores (P?=?0.001 and P?<?0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β?=??0.56, P?<?0.001). No significant difference was observed between two groups in the frequency of side effects.

Conclusion

These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted.

Clinical trial registry name and registration number

Iranian registry of clinical trials www.irct.ir, IRCT201107281556N26     

Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial

Background

Cumulative evidence from epidemiological, preclinical and clinical studies suggests estrogens may have psychoprotective effects in schizophrenic patients. Selective Estrogen Receptor Modulators could have therapeutic benefits in schizophrenia for both sexes without being hazardous to gynecological tissues or having feminizing effects. Few studies have been conducted regarding the effects of raloxifene on postmenopausal women suffering from schizophrenia. We conducted this placebo-controlled trial to compare the add-on effect of raloxifene to risperidone versus risperidone with placebo.

Methods

This was an 8-week, parallel-group, placebo-controlled trial undertaken at two universities affiliated psychiatric Hospitals in Iran. Forty-six postmenopausal women with the definite diagnosis of schizophrenia were enrolled in the study. Patients received risperidone (6 mg/day in 3 divided doses) combined with either placebo (N = 23) or 120 mg/day of raloxifene (N = 23) for 8 weeks. Patients were assessed by a psychiatrist at baseline and at 2 and 8 weeks after the start of medical therapy. Efficacy was defined as the change from baseline to endpoint in score on Positive and Negative Syndrome Scale (PANSS).

Results

For PANSS scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.77, p = 0.18]. For positive subscale scores, there was marginal significant interaction between intervention type and time [F (2, 47) = 2.93, p = 0.06] and there was substantial main effect for time [F (2, 47) = 24.39, p = 0.001] within both groups showing reduction in positive subscale scores across the three time periods. In addition, the main effect comparing two types of intervention was significant [F (1, 48) = 3.78, p = 0.02]. On the other hand, for negative subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.43, p = 0.23]. For general subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 0.03, p = 0.86].

Conclusions

According to our findings, raloxifene as an adjunctive treatment to risperidone was only superior in improvement of positive symptoms and it was not effective in treating negative and general psychopathology symptoms.

Trial registration

The trial was registered at the Iranian registry of clinical trials: IRCT201205131556N42