Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran.

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and ß-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating ß-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of ß-thalassaemia trait was the major potential risk factor in this population.

Efficacy of prophylaxis and genotype-phenotype correlation in patients with severe Factor X deficiency in Iran.

We aimed to evaluate the effect of regular prophylaxis with a Factor X (FX) concentrate for patients with severe FXD in Iran and to assess the correlation of the genotype and phenotype in these patients. Ten patients with severe FXD (FX activity <1%) were enrolled and characterized during 2010-2011. Prophylaxis with 20 IU FX P Behring per kg body weight was administered once a week. FX levels, were monitored at baseline, 15 and 30 min, 1, 3, 6, 12, 24, 48, 72 and 96 h after starting prophylaxis. All patients were followed for 1 year. The mean age of the patients was 15 ± 7.8 years (age range of: 6-27 years). One patient had anaphylactic reaction after the first infusion, and the treatment was stopped. During one-year follow-up after starting prophylaxis, no bleeding symptoms occurred in any patient who tolerated and remained on the prophylaxis programme and all of them had a FX level of 1% or above. The maximum level of FX activity has been observed at 15 min after starting prophylaxis. A level of 1.5-3.5% was detected after 96 h. Homozygous mutations p.Arg40Thr (Arg-1Thr), p.Gly51Arg and p.Glu69Lys were detected in patients with intracranial haemorrhage. In our patients, significant decrease in symptoms without any complication after administration of FX, was demonstrated in all except one patient who had an anaphylactic reaction. It seems that the dose of 20 IU kg(-1) could be probably the best choice for patients with severe FXD, who require regular prophylaxis.

Polymorphisms associated with sickle cell disease in Southern Iran.

Sickle cell disease (SCD) is an inherited autosomal recessive disorder. We aimed to describe the spectrum of haplotyes of BS-gene and to investigate a relationship with disease phenotype in patients with SCD in Southern Iran. We didn't find any significant association between BS-globin gene haplotypes and clinical severity of the disease in an Iranian population. The exact mechanism by which the BS-globin gene polymorphism affects clinical presentation is not obvious; however, further detailed studies at the molecular level, with a larger sample size are required to show the mechanisms that influence the clinical presentation of SCD in Iranian population.

Prevalence of pyruvate kinase deficiency among the south Iranian population: quantitative assay and molecular analysis.

We present the results of screening for pyruvate kinase (PK) deficiency on a cohort of 146 patients pre-selected from 4017 individuals by hematological index analysis. On average the PK activity levels measured in this cohort study were about 1.9% IU/g Hb while the activity measured in 85 healthy adults with normal erythrocyte indexes was in the range of 3.9-9.8 IU/g Hb. We were able to define 14 different mutations in the coding sequence of the R-PK gene in 74 individuals with low enzyme activity. The most common were the G1168A and G1529A mutations at exon 11 occurring in 54% of the cases. Other mutations occurring more than once were C1492T, C1456T, G1291A, C1594T, G787A, G994A, and G1010C. The polymorphism at nt 1705 was in linkage disequilibrium with the A and C polymorphism, which indicated a multi-centric origin of the mutation. Further study of the promoter region and intron/exon boundary is under investigation.

AlphaIIbG236E causes Glanzmann thrombasthenia by impairing association with beta3.

Glanzmann thrombasthenia (GT) is a recessively inherited bleeding disorder caused by the quantitative or qualitative deficiency of the platelet fibrinogen receptor, integrin alphaIIbbeta3. The N-terminal domain of the alphaIIb subunit is folded in a beta-propeller that plays the role of binding fibrinogen and associating with the ligand-binding region of beta3. Analysing the mutations of Italian GT patients we found that a patient had a alphaIIb G236E missense substitution that substitutes a glycine from the highly conserved PhiPhiGPhi motif of blade 4 of the beta-propeller. To verify experimentally the effect of the substitution of glycine 236 human embryonic kidney (HEK) cells were transfected with normal or mutated alphaIIb in conjunction with normal beta3. Using flow cytometry analysis we found the percentage of HEK cells transfected with alphaIIbG236Ebeta3 that reacted with anti alphaIIbbeta3 was very low. In HEK cells transfected with either alphaIIbbeta3 or alphaIIbG236Ebeta3 and lysed, when immunoblotting was done in non-reducing conditions a band reacting with an antibody against alphaIIb was present in both lysates, although less intense in cells transfected with alphaIIbG236Ebeta3. In reducing condition alphaIIb from cells transfected with alphaIIbbeta3 was nearly all mature, while in cells transfected with alphaIIbG236Ebeta3 the ratio pro-alphaIIb: alphaIIb was 1 : 1, with signs of degradation of the mutated protein. Cell lysates were then immunoprecipitated with antibodies against alphaIIb and immunoblotted with an antibody reacting with beta3. While in immunoblots from cells transfected with alphaIIbbeta3 a band corresponding to beta3 was strongly detectable, in immunoblots originating from cells transfected with alphaIIbG236Ebeta3 no band at the same level of normal beta3 was detected. Immunofluorescence studies showed accumulation of alphaIIbG236Ebeta3 in the endoplasmic reticulum and minimal transport to the Golgi. In conclusion we demonstrated that the alphaIIbG236E mutation causes GT by impairing the association with beta3 during biogenesis of the receptor.

Intravenous versus intramuscular atropine in ECT.

Twelve patients receiving ECT consented to random assignment to either intravenous or intramuscular administration of atropine for a total of 48 ECTs. There were no statistically significant differences between routes of administration in heart rate, blood pressures, or sialorrhea, but intravenous administration eliminated one injection per treatment and the development of dry mouth and tachycardia between the intramuscular injection and ECT. The authors recommend that atropine for ECT be administered intravenously.

Effect of rapid weight loss with supplemented fasting on serum electrolytes, lipids, and blood pressure.

The effect of rapid weight reduction with supplemented fasting was studied in a group of 46 individuals with moderate to severe obesity. The preparation used contained a mixture of protein, carbohydrate, and essential fatty acids providing 420 kcal daily. It was supplemented with a complement of electrolytes, minerals, and vitamins.Serum concentrations of electrolytes, urea nitrogen, creatinine, uric acid, glucose, cholesterol, and triglycerides were measured prior to the onset of the study and at two-week intervals for a six-week study period. In addition, blood pressure, heart rate, and body weight were recorded regularly. A mild and transient fall in serum bicarbonate concentration and a rise in uric acid level was observed.In contrast to other regimens, hypokalemia was not observed in the present study. In fact, serum K+ concentration rose slightly while serum Na+ concentration remained virtually unchanged. There was a transient rise in serum creatinine concentration followed by a fall to values below the baseline. Serum glucose, cholesterol and triglyceride levels, blood pressure, and heart rate decreased significantly. Body weight fell from 232.7 ± 58 lb at the onset of the study to 176.4 ± 47.9 lb at the conclusion of the study.The protocol was well tolerated and the side effects were mild and infrequent. In conclusion, the present protocol provides a safe and effective means for rapid weight reduction in individuals with moderate to marked obesity without producing severe electrolyte disturbances seen with other modalities.

Combined α-thalassemia and Hemoglobin J-Iran (ß77 His → Asp). A Family Study in southern Iran.

We report a 23-year-old man and three members of his family with Hb J-Iran confirmed by electrophoresis, chain separation by high performance liquid chromatography and sequencing. Alpha thalassemia was also confirmed in two family members. The substitution at ß77 led to a higher negative charge of the ßJ-Iran subunit, which enhanced its electrostatic attraction for the normal positively-charged α subunit. Therefore, more Hb J-Iran than Hb A forms in the red blood cells of heterozygotes. In α-thalassemia, the more attractive ßJ-Iran subunit outcompetes ßA subunits in forming assemblies with deficient α subunits, so even more Hb J-Iran was formed.

Benefits of cardiac rehabilitation on lipid profile in patients with coronary artery disease.

This cross-sectional study was performed in patients following coronary interventions, to evaluate the effect of cardiac rehabilitation on functional capacity, maximum heart rate on exercise and serum lipid profiles. Consecutive patients after coronary artery intervention randomly referred to cardiac rehabilitation. All patients underwent based exercise tolerance test to define exercise capacity. Blood samples were obtained to measure based plasma lipid profiles and nutritional counseling provided to all participants. Also, psychological evaluation was performed with the some documented questionnaire to explore emotional, behavioral and psychological state. After completion of cardiac rehabilitation in all patients, reassessment of work capacity, plasma lipid profile and psychological state were performed. After cardiac rehabilitation for 8-12 weeks, functional capacity improved in 83% of patients (p<0.001) and maximal heart rate at the same time on exercise decreased in 72%. The average time on treadmill was 7.76 min before and 9.56 min after cardiac recreation (p<0.001). After cardiac rehabilitation, plasma total cholesterol, low-density lipoprotein and triglyceride significantly decreased. At the end, 97% of patients returned to work and had sense of well-being. Cardiac rehabilitation has important impacts on improving functional capacity, well being sensation, return to work and decreasing serum lipid profiles in coronary patients.

Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase [G6PD]deficiency and beta-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years [51 males, 83 females]. Low serum ferritin [< 12 ng/dL] was present in 17.9% of children [21.7% in females and 11.8% in males]. Low haemoglobin [Hb]correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 >/= 3.5 g/ dL, indicating beta-thalassaemia trait [10.8% in females and 7.8% in males]. Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females.Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of beta-thalassaemia trait was the major potential risk factor in this population

La présente étude a évalué la prévalence de l'anémie ferriprive,du déficit en glucose-6-phosphate déshydrogénase et de la bêta-thalassémie mineure chez des enfants nomades et migrants arabes dans le sud de la République islamique d'Iran. Des échantillons de sang de 134 écoliers de moins de 18 ans ont été analysés [51 garçons, 83 filles]. Des taux de ferritine sérique faibles [< 12 ng/dL] ont été observés chez 17,9 % des enfants [21,7 % chez les filles et 11,8 % chez les garçons]. Un faible taux d'hémoglobine [Hb] était significativement corrélé à un faible taux de ferritine sérique. Seul un enfant était atteint de déficit en glucose-6-phosphate déshydrogénase. Au total,9,7 % des enfants présentaient un taux d’HbA2 supérieur ou égal à 3,5 g/dL, signe d'une bêta-thalassémie mineure [10,8 % des filles et 7,8 % des garçons]. Le taux moyen de fer sérique, de la ferritine sérique et la capacité de liaison du fer total étaient similaires chez les deux sexes. Le taux de ferritine sérique était aussi précis que le taux d’Hb pour le diagnostic de l'anémie ferriprive. La forte prévalence de la bêta-thalassémie mineure représentait le principal facteur de risque dans cette population

Second international collaborative study evaluating performance characteristics of methods measuring the von Willebrand factor cleaving protease (ADAMTS-13).

BACKGROUND: Over the last 4 years ADAMTS-13 measurement underwent dramatic progress with newer and simpler methods. AIMS: Blind evaluation of newer methods for their performance characteristics. DESIGN: The literature was searched for new methods and the authors invited to join the evaluation. Participants were provided with a set of 60 coded frozen plasmas that were prepared centrally by dilutions of one ADAMTS-13-deficient plasma (arbitrarily set at 0%) into one normal-pooled plasma (set at 100%). There were six different test plasmas ranging from 100% to 0%. Each plasma was tested 'blind' 10 times by each method and results expressed as percentage vs. the local and the common standard provided by the organizer. RESULTS: There were eight functional and three antigen assays. Linearity of observed-vs.-expected ADAMTS-13 levels assessed as r2 ranged from 0.931 to 0.998. Between-run reproducibility expressed as the (mean) CV for repeated measurements was below 10% for three methods, 10-15% for five methods and up to 20% for the remaining three. F-values (analysis of variance) calculated to assess the capacity to distinguish between ADAMTS-13 levels (the higher the F-value, the better the capacity) ranged from 3965 to 137. Between-method variability (CV) amounted to 24.8% when calculated vs. the local and to 20.5% when calculated vs. the common standard. Comparative analysis showed that functional assays employing modified von Willebrand factor peptides as substrate for ADAMTS-13 offer the best performance characteristics. CONCLUSIONS: New assays for ADAMTS-13 have the potential to make the investigation/management of patients with thrombotic microangiopathies much easier than in the past.

Genetic characterization of patients with Bernard-Soulier syndrome and their relatives from Southern Iran.

Bernard-Soulier syndrome (BSS) is a rare recessively inherited bleeding disorder caused by the deficiency of the platelet glycoprotein (Gp) complex Ib/IX/V that is the von Willebrand factor receptor on platelets. In patients suffering from BSS platelet adhesion is typically impaired, while platelet aggregation is normal; macrothrombocytopenia is a common feature. In this study three different families from Southern Iran were investigated. GpIb/IX/V platelet expression as detected by flow cytometry was less than 2% of normal in six cases and 12% in the remaining one. Platelet count was 35,000 platelets/microliter and iron deficiency anemia was common. All patients suffered from mucocutaneous bleeding at presentation and were born from consanguineous marriages. Genetic analysis demonstrated the presence of the same GpIX Phe55Ser missense mutation in two families and of a single base insertion (GP1BA C3221 ins), a never described mutation causing a frameshift in the GpIbalpha gene, in the third family. Among the family members studied several heterozygotes were identified. None of them, with one exception, had macrothrombocytopenia. In one family a slight reduction of GpIb/IX/V expression was observed.

Glanzmann thrombasthenia and Bernard-Soulier syndrome in south Iran.

Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) are two rare inherited disorders of platelet function. In this study, we report the demographic, clinical and biological characteristics of 23 patients with GT and of seven patients with BSS from southern Iran who had been followed for many years but fully characterized only recently, when platelet aggregation tests and flow cytometric studies became available for the first time in the country. We found a high prevalence of both diseases that can be explained by the high rate of consanguineous marriages in south Iran. Patients affected by GT and BSS suffer mainly from mucocutaneous bleedings causing anemia and transfusion requirements.

A TSH secreting pituitary tumour causing hyperthyroidism: presentation of a case and review of the literature.

A 45 year old male with a 12 year history of mild hyperthyroidism and a pituitary tumour is presented. He had both clinical and laboratory evidence of hyperthyroidism and his serum TSH was persistently and markedly elevated. A TRH test resulted in no further rise in serum TSH. No evidence of pituitary or peripheral endocrine deficiencies existed and prolactin levels were normal. Craniotomy was performed and a pituitary adenoma was removed. On light microscopy, it was mostly composed of chromophobes. However, occasional granulated cells were observed, and on electron microscopy, most of the cells contained fine granules, which suggested possible thyrotroph origin of the tumour. One week post-operatively the patient's serum TSH returned to normal. Again, TRH produced no response in TSH. The patient became hypothyroid by clinical and laboratory findings and is currently on thyroid replacement therapy. The previously reported TSH secreting tumours associated with hyperthyroidism are reviewed.

Severe hyperkalemia caused by indomethacin and potassium supplementation.

Treatment with a combination of indomethacin and potassium chloride supplementation resulted in severe hyperkalemia in a patient with Bartter's syndrome. The clinical and electrocardiographic findings and hyperkalemia improved promptly with intravenous administration of sodium bicarbonate, glucose, and insulin, discontinuation of the potassium supplement, and reduction of the indomethacin dose. This case suggests that life-threatening hyperkalemia can occur when indomethacin and potassium supplementation are prescribed simultaneously in Bartter's syndrome.

Effect of rapid weight loss with supplemented fasting on liver tests.

We monitored serum liver tests in 46 obese persons undergoing rapid weight reduction with a supplemented fasting diet containing a mixture of protein, glucose, essential fatty acids, vitamins, and minerals. Levels of SGOT, SGPT, alkaline phosphatase, lactic dehydrogenase (LDH) and serum concentrations of bilirubin, total protein, and albumin were within normal limits at the onset of the study. SGOT, SGPT, LDH, alkaline phosphatase, and serum total bilirubin rose mildly but significantly 2 weeks after the institution of the supplemented fasting program. Thereafter, the values began to decline, approaching baseline levels within 4-6 weeks despite the continued dietary restrictions. We conclude that rapid weight reduction using a supplemented fasting regimen can lead to a mild hepatic test abnormality. The resultant liver test abnormalities are transient and reversible and may not require extensive diagnostic investigations.

Epidural butorphanol augments lidocaine sensory anesthesia during labor.

To determine the efficacy and safety of epidural butorphanol combined with lidocaine, 50 healthy parturients were studied during labor and delivery. All patients received a test dose of 3 ml 1.5% lidocaine with 1:200,000 epinephrine. Patients were then randomly assigned to receive 7 ml of one of two epidural regimens in a double-blind fashion: Group 1 patients received 1.5% lidocaine plus 1 mg butorphanol plus 1:300,000 epinephrine; Group 2 patients received 1.5% lidocaine plus 1:300,000 epinephrine. Each group consisted of 25 patients. The study ended at the time of redosing. All subsequent epidural injections were made with one bolus of plain 0.25% bupivacaine followed by continuous infusion of 0.125% bupivacaine. Duration of anesthesia was significantly longer for Group 1 compared to Group 2 (p less than 0.01), 124 +/- 8 minutes versus 99 +/- 6 minutes (mean +/- SEM). There were no difference between groups in duration of first and second stages of labor, method of delivery or neonatal outcome. Umbilical cord acid-base status and neurologic adaptive capacity scores did not differ significantly between the two groups. The authors conclude that adding small doses of butorphanol to epidural lidocaine during labor is effective and safe.

Continuous infusion epidural anesthesia during labor: a randomized, double-blind comparison of 0.0625% bupivacaine/0.002% butorphanol and 0.125% bupivacaine.

The efficacy of pain relief and the maternal and neonatal effects of continuous epidural infusion of 0.0625% bupivacaine/0.002% butorphanol was compared with the infusion of 0.125% bupivacaine alone in a randomized, double-blind study of 32 women in labor. A test dose of 2 ml 0.5% bupivacaine was given to every patient and followed by two epidural regimens in randomized, double-blind manner. Group B-B (bupivacaine/butorphanol) patients received 7.5 ml 0.125% bupivacaine plus 1 mg butorphanol (0.5 ml) followed by an infusion of 0.0625% bupivacaine/0.002% butorphanol at a rate of 12 ml/hour; Group B (bupivacaine alone) patients received 8 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine at a rate of 12 ml/hour. A bolus of 5 ml 0.125% bupivacaine or 0.0625% bupivacaine was given to Group B or B-B, respectively, if additional pain relief was required. Infusion of B-B combination resulted in similar pain relief and fewer patients with motor block than bupivacaine alone; 12% versus 38% in Groups B-B and B, respectively, had motor weakness. A smaller dose of bupivacaine was used in the B-B group compared to the B group; 71 +/- 14 versus 99 +/- 13 mg (mean +/- SEM; p less than 0.05). Progress of labor and the mode of delivery did not differ significantly between the two groups. All infants were vigorous and had normal acid-base status and neurologic adaptive capacity scores. Butorphanol appears to be useful as an adjunct to epidural bupivacaine for continuous epidural infusion during labor without adversely affecting the mother or the neonate.