Importance of ionized magnesium measurement for monitoring of citrate- anticoagulated plateletpheresis

BACKGROUND: The infusion of citrate during apheresis may affect the levels of ionized magnesium in the blood. Hypomagnesemia and concomitant hypocalcemia could influence the parathormone response and could be responsible for some of the symptoms observed during apheresis. STUDY DESIGN AND METHODS: The study reports measurement of ionized magnesium by the new ion-selective electrode technique in response to citrate infusion in 15 donors undergoing continuous flow high-yield plateletpheresis. The monitoring included measurement of ionized calcium and parathormone every 30 minutes during the 120-minute apheresis (plus the next 30 minutes to assess recovery). RESULTS: Ionized magnesium fell by 30 +/− 4 percent (mean +/− SD, p<0.01), which contrasts with minor changes in total concentrations. Comparison of variations in the levels of ionized and total magnesium found major formation of complexes during citrate infusion. Ionized calcium fell by 15 +/− 3 percent (p<0.01), while parathormone peaked at 356 +/− 114 percent (p<0.01) of initial value after 30 minutes. Ionized cations and parathormone recovered by more than 50 percent within 30 minutes of the end of apheresis. CONCLUSION: An acute and steep drop in ionized magnesium occurs during citrate administration. The measurement of ionized magnesium should be included in future prospective studies of donor safety and parathormone regulation during apheresis.     

Oocyte morphology does not affect fertilization rate, embryo quality and implantation rate after intracytoplasmic sperm injection

In this study, we compared the fertilization rate and embryo quality after intracytoplasmic sperm injection (ICSI) as they relate to oocyte morphology. A total of 654 ICSI cycles yielding 5903 metaphase II oocytes were observed. The oocytes retrieved in these cycles were divided into (i) normal oocytes, (ii) oocytes with extracytoplasmic abnormalities (dark zona pellucida and large perivitelline space), (iii) oocytes with cytoplasmic abnormalities (dark cytoplasm, granular cytoplasm, and refractile body), (iv) oocytes with shape abnormalities, and (v) oocytes with more than one abnormality (double and triple abnormalities). Intracytoplasmic vacuoles and aggregates of smooth endoplasmic reticulum were not recorded separately. The fertilization rate and quality of morphologically graded embryos did not differ between the groups. There were 77 cycles where all transferred embryos were derived from abnormal oocytes, and 164 cycles where all embryos were derived from normal oocytes. These cycles were studied further. The two groups were comparable regarding mean female age, duration of infertility, duration of ovarian stimulation, number of ampoules of gonadotrophin injected, and number of oocytes retrieved. Two clinical pregnancy rates (44.4 versus 42.1%) and implantation rates per embryo (10.3 versus 13.2%) were similar. In conclusion, in couples undergoing ICSI, abnormal oocyte morphology is not associated with a decreased fertilization rate or unfavourable embryo quality. Furthermore, embryos derived from abnormal oocytes yield similar clinical pregnancy and implantation rates when transferred compared with embryos derived from normal oocytes.      

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH- stimulated patients.      

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy—based on creatinine level, proteinuria and disease activity—was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.     

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Essential tremor is one of the most frequent movement disorders in humans (1). It is characterized primarily by postural or kinetic tremor of the arms and hands, but head, legs, voice, and other regions of the body may also be affected (2). The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations (1). Familial essential tremor is genetically heterogeneous. Genetic linkage studies of multiply affected families revealed three genomic regions segregating with the condition, on chromosomes 3q13 [ETM1; Online Mendelian Inheritance in Man (OMIM) 190300], 2p22-24 (ETM2; OMIM 602134), and 6p23 (ETM3; OMIM 611456) (3–5). No clearly causal mutations have been identified in these regions, although the common variant DRD3 p.S9G in the ETM1 region has been proposed as a risk factor and HS1BP3 p.A265G in the ETM2 region appeared in two multiply affected families (6, 7). Genomewide association studies of essential tremor reported associations with common variants in an intron of LINGO1 and in an intron of SLC1A2 (8–10). Recently, DNAJC13 p.N855S, which had been identified in Parkinson disease patients, was also found in two unrelated patients with essential tremor (11). Nonsense mutation p.Q290X in the RNA-binding protein FUS was identified by whole exome sequencing in a large family with essential tremor (ETM4; OMIM 614782) (12). Screening other subjects with essential tremor for FUS revealed two rare missense variants, suggesting that mutations in FUS explain a subset of cases with the condition (13, 14).In this study, we examined a six-generation family segregating essential tremor, and in multiple relatives, essential tremor as a feature of Parkinson disease. We carried out whole exome sequencing of genomic DNA from three severely affected family members and subsequent pedigree analysis to identify the genetic basis of essential tremor and Parkinson disease in the family.     

Safety of fluoxetine treatment in a case of acute intermittent porphyria

Acute intermittent porphyria (AIP) is a metabolic disease characterized by recurrent attacks of neurological and psychiatric dysfunction. It is a rare disorder of heme metabolism that usually presents with abdominal pain, gastrointestinal symptoms and autonomic nervous system disturbances. Exposure to certain drugs, dieting, starvation and infection during pregnancy may precipitate AIP attacks. Psychiatric manifestations of AIP include mood changes, organic brain syndrome and psychosis. Here, we present a 21-year-old female patient with AIP and major depression. She had a caesarean section under general anesthesia with pentothal and her recovery time from anesthesia took longer than usual. She had a blood transfusion because of severe anemia following the operation. Three days after her discharge she was readmitted to the hospital with confusion and seizure. It was her first AIP attack and it started 6 days after caesarean section. Two months after her first attack, we saw her for anxiety and depressive symptoms. She was in severe anxiety and depression and she was put on fluoxetine (20 mg/day liquid form). Following the treatment she did not develop any other porphyria attack. Her symptoms vanished and she improved functionally. She stayed on fluoxetine for 6 months without any new AIP attack. Despite limited data regarding fluoxetine therapy in porphyria patients, it seems to be safe for the treatment of depressive and anxiety symptoms in these patients.     

Speaker Abstracts

Narcolepsy is a rare disorder characterised by sleep disturbances, cataplexy, sleep paralysis and hypnagogic, hypnopompic hallucinations. Although several treatment modalities, such as tricyclic antidepressants or selective serotonin reuptake inhibitors, have been used to treat different symptoms, there is no definite treatment for narcolepsy. Modafinil or amphetamine-like stimulants, such as dexamphetamine or methylphenidate, are used to treat sleepiness. Our case was a 58-year-old woman who was diagnosed as narcolepsy cataplexy syndrome. Her Epworth Sleepiness Scale (ESS) score was 14 and Beck Depression Inventory (BDI) score was 29 in the first evaluation. Imipramine and modafinil were begun for the treatment, but there was no improvement in her symptoms. Subsequently, bupropion was started at 150 mg/day and then dosage was increased to 300 mg/day. She was asymptomatic at the end of 3 months. To our knowledge, this is the second depressive narcoleptic patient who has responded to 300 mg/day of bupropion.     

Aortitis in a patient with psoriatic arthritis

Aortitis, inflammation of the aortic tissue, is most commonly caused by vasculitic rheumatic conditions, and less frequently infectious organisms. Involvement of the aorta is well defined in HLA-B27-associated spondyloarthropathies such as long-standing ankylosing spondylitis and Reiter's syndrome. However, unlike other spondyloarthropathies, aortic involvement or true aortitis is not a feature of psoriatic arthritis and has been reported in only a few cases. Herein, we report the case of a 22?year-old woman with psoriatic arthritis who developed descending aortitis while using tumor necrosis factor inhibitors.