Evaluation of self-medication prevalence, diagnosis and prescription in migraine in Kerman, Iran

Objective: To investigate different diagnosis aspects, prescribed drugs and self-medications of migraine in Iran. Methods: We selected 210 migraineurs from high school and university students in Kerman, Iran over a period of 6 months in 2002 by multistage randomized screening based on the International Headache Society criteria. We classified them into 2 groups on the basis of whether they had consulted a physician or not. We then evaluated the physician prescriptions, and prevalence of self-medications. Results: Only 49 of migraineurs consulted a physician, and only 53 were correctly diagnosed by physicians according to the International Headache Society criteria. Our study shows that 69 of general practitioners diagnoses were wrong. In spite of indications for prophylactic treatment, it was not prescribed in 76 of the patients, and 50 of the general practitioners prescribed it without any indications. Furthermore, 91 of patients used self-medication; Acetaminophen and Codeine were the most common. Conclusion: General practitioners' misdiagnosis and mismanagement of the migraineurs, and easy access to various drugs in Iran, have led to a high rate of self-medication. Self-medication with Codeine, with regard to its side effects, such as increase of secondary headaches and dependency is the major problem. Consequently, medical education systems, physician reevaluating methods, and the concept of self-medication among patients have to be revised

Evaluation of self-medication prevalence, diagnosis and prescription in migraine in Kerman, Iran

Objective: To investigate different diagnosis aspects, prescribed drugs and self-medications of migraine in Iran. Methods: We selected 210 migraineurs from high school and university students in Kerman, Iran over a period of 6 months in 2002 by multistage randomized screening based on the International Headache Society criteria. We classified them into 2 groups on the basis of whether they had consulted a physician or not. We then evaluated the physician prescriptions, and prevalence of self-medications. Results: Only 49 of migraineurs consulted a physician, and only 53 were correctly diagnosed by physicians according to the International Headache Society criteria. Our study shows that 69 of general practitioners diagnoses were wrong. In spite of indications for prophylactic treatment, it was not prescribed in 76 of the patients, and 50 of the general practitioners prescribed it without any indications. Furthermore, 91 of patients used self-medication; Acetaminophen and Codeine were the most common. Conclusion: General practitioners' misdiagnosis and mismanagement of the migraineurs, and easy access to various drugs in Iran, have led to a high rate of self-medication. Self-medication with Codeine, with regard to its side effects, such as increase of secondary headaches and dependency is the major problem. Consequently, medical education systems, physician reevaluating methods, and the concept of self-medication among patients have to be revised

Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia.

The development of hindlimbs in tetrapod species relies specifically on the transcription factor TBX4. In humans, heterozygous loss-of-function TBX4 mutations cause dominant small patella syndrome (SPS) due to haploinsufficiency. Here, we characterize a striking clinical entity in four fetuses with complete posterior amelia with pelvis and pulmonary hypoplasia (PAPPA). Through exome sequencing, we find that PAPPA syndrome is caused by homozygous TBX4 inactivating mutations during embryogenesis in humans. In two consanguineous couples, we uncover distinct germline TBX4 coding mutations, p.Tyr113 <sup>∗</sup> and p.Tyr127Asn, that segregated with SPS in heterozygous parents and with posterior amelia with pelvis and pulmonary hypoplasia syndrome (PAPPAS) in one available homozygous fetus. A complete absence of TBX4 transcripts in this proband with biallelic p.Tyr113 <sup>∗</sup> stop-gain mutations revealed nonsense-mediated decay of the endogenous mRNA. CRISPR/Cas9-mediated TBX4 deletion in Xenopus embryos confirmed its restricted role during leg development. We conclude that SPS and PAPPAS are allelic diseases of TBX4 deficiency and that TBX4 is an essential transcription factor for organogenesis of the lungs, pelvis, and hindlimbs in humans

Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway

Contains fulltext : 136372.pdf (Publisher’s version ) (Closed access)Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by a recognizable pattern of severe malformations leading to prenatal or early postnatal lethality. Homozygous mutations in PHGDH, a gene involved in the first and limiting step in L-serine biosynthesis, were recently identified as the cause of the disease in three families. By studying a cohort of 12 unrelated families affected by NLS, we provide evidence that NLS is genetically heterogeneous and can be caused by mutations in all three genes encoding enzymes of the L-serine biosynthesis pathway. Consistent with recently reported findings, we could identify PHGDH missense mutations in three unrelated families of our cohort. Furthermore, we mapped an overlapping homozygous chromosome 9 region containing PSAT1 in four consanguineous families. This gene encodes phosphoserine aminotransferase, the enzyme for the second step in L-serine biosynthesis. We identified six families with three different missense and frameshift PSAT1 mutations fully segregating with the disease. In another family, we discovered a homozygous frameshift mutation in PSPH, the gene encoding phosphoserine phosphatase, which catalyzes the last step of L-serine biosynthesis. Interestingly, all three identified genes have been previously implicated in serine-deficiency disorders, characterized by variable neurological manifestations. Our findings expand our understanding of NLS as a disorder of the L-serine biosynthesis pathway and suggest that NLS represents the severe end of serine-deficiency disorders, demonstrating that certain complex syndromes characterized by early lethality could indeed be the extreme end of the phenotypic spectrum of already known disorders

Mutations in <em>ATP6V1E1</em> or <em>ATP6V1A</em> cause autosomal-recessive cutis laxa.

Defects of the V-type proton (H+) ATPase (V-ATPase) impair acidification and intracellular trafficking of membrane-enclosed compartments, including secretory granules, endosomes, and lysosomes. Whole-exome sequencing in five families affected by mild to severe cutis laxa, dysmorphic facial features, and cardiopulmonary involvement identified biallelic missense mutations in ATP6V1E1 and ATP6V1A, which encode the E1 and A subunits, respectively, of the V1 domain of the heteromultimeric V-ATPase complex. Structural modeling indicated that all substitutions affect critical residues and inter- or intrasubunit interactions. Furthermore, complexome profiling, a method combining blue-native gel electrophoresis and liquid chromatography tandem mass spectrometry, showed that they disturb either the assembly or the stability of the V-ATPase complex. Protein glycosylation was variably affected. Abnormal vesicular trafficking was evidenced by delayed retrograde transport after brefeldin A treatment and abnormal swelling and fragmentation of the Golgi apparatus. In addition to showing reduced and fragmented elastic fibers, the histopathological hallmark of cutis laxa, transmission electron microscopy of the dermis also showed pronounced changes in the structure and organization of the collagen fibers. Our findings expand the clinical and molecular spectrum of metabolic cutis laxa syndromes and further link defective extracellular matrix assembly to faulty protein processing and cellular trafficking caused by genetic defects in the V-ATPase complex