Metabolite phantom correction of the nonuniform volume-selection profiles in MR spectroscopic imaging: application to temporal lobe epilepsy

BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.     

Effect of life-style factors on incidence of erectile dysfunction

We estimated the incidence of erectile dysfunction (ED) in a population-based sample during 5-y follow-up and determined how the rate was affected by sociodemographic and life-style factors. The target population comprised all men aged 50, 60 or 70 y residing in the city of Tampere or 11 surrounding municipalities in Finland at the start of follow-up. A questionnaire was mailed to 3143 men in 1994 and to 2864 in 1999. The follow-up sample consisted of 1442 men who responded to both baseline and follow-up questionnaires. We estimated the effect of sociodemographic and life-style factors on the incidence of ED among the 1130 men free of ED at baseline. We found no differences in the incidence of ED by the level of education, marital status, urban/rural place of residence, amount of alcohol and coffee consumption. Obesity (rate ratio (RR)=1.7, 95% confidence interval (CI): 1.1-2.5) and current smoking (RR=1.5, 95% CI: 0.9-2.2) increased the incidence of ED. Current smokers free of comorbidity were also at higher risk of ED (RR=1.3, 95% CI: 0.8-2.1), but no effect was observed among past smokers. Our results indicate that sociodemographic and life-style factors, except age and obesity, have little influence on ED.     

Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations

Chorionic gonadotropin (CG) is an essential signal in establishment and maintenance of pregnancy in humans and higher primates. A G-to-A transition in exon 3 of human CGbeta gene 5, changing the naturally occurring valine residue to methionine in codon 79 (Val(79)Met) has been reported at carrier frequency 4.2% in a random population from the Midwest of the United States. The biological activity of the variant hCG was similar to that of wild-type (WT) hCG. However, the Val(79)Met beta-subunit displayed impaired ability to assemble with alpha-subunit, and the amount of hCG alpha/beta heterodimers formed and secreted by transfected cells was seriously impaired in the previous study. Because of these functional implications we found it important to study the occurrence of the Val(79)Met hCGbeta variant in other populations. By using a PCR-RFLP method, a search for the Val(79)Met hCGbeta variant was carried out on a total of 580 DNA samples from five European populations (Finland, Denmark, Greece, Germany and the UK). The results demonstrated an absence of the polymorphism in these populations. Hence, the naturally occurring variant (Val(79)Met) of the hCGbeta gene 5, found previously at high frequency in the US, is clearly less common, or absent, in the European populations studied.     

Domestically acquired Campylobacter infections in Finland

Campylobacter jejuni isolates (n = 533) from domestic cases diagnosed in Finland during a 3-month peak period were studied. The highest rate was observed among those 70-74 years of age. Domestic C. jejuni isolates were especially frequent in the eastern districts. Six serotypes covered 61% of all C. jejuni isolates.     

Gonioscopic view of the trabeculo-Descemet's membrane after deep sclerectomy

PURPOSE: To study the appearance of the trabeculo-Descemet's membrane (TDM) after deep sclerectomy with collagen implant (DSCI). METHODS: All patients who underwent a successful DSCI for open-angle glaucoma were included in a non-randomized clinical study. Gonioscopy was performed between 6 and 12 months postoperatively in all patients. RESULTS: Gonioscopy was performed in 42 eyes of 38 patients after a mean follow-up time of 8.3 +/- 2.5 months after DSCI. The diagnosis was chronic open-angle glaucoma in 16 eyes and exfoliative glaucoma in 24 eyes. One patient had pigmentary glaucoma and one had normal tension glaucoma. None of the patients were on glaucoma medication postoperatively. Synechias to the TDM were seen in five eyes. Pigment accumulation to the TDM was seen in nine eyes, four of which had capsular glaucoma, three had primary open-angle glaucoma, one had pigmentary glaucoma and one had normal tension glaucoma. Puncture holes at the TDM were seen in all eight eyes in which Nd:YAG laser goniopuncture had been performed. CONCLUSION: Postoperative changes, which may go unnoticed without routine gonioscopy, occur at the TDM after deep sclerectomy with collagen implant. Pigment accumulates relatively shortly after surgery. Whether or not these changes are progressive remains unknown. Careful follow-up after deep sclerectomy is necessary and should include routine gonioscopy.     

Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19

Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (+/- standard deviation) S/R ratio for citalopram was 0.67 +/- 0.25 and for desmethylcitalopram, 0.68 +/- 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.     

<Emphasis Type="Italic">CYP2C9</Emphasis> genetic variants and losartan oxidation in a Turkish population

Objective Cytochrome P₄₅₀ 2C9 (CYP2C9) is a polymorphic enzyme catalysing the metabolism of several important drugs. Losartan has recently been suggested as a selective probe for CYP2C9 metabolic activity. The aim of the study was to determine the activity of CYP2C9, using losartan as a probe drug, in relation to CYP2C9 genotype in healthy Turkish subjects.Methods A single oral dose of 25 mg losartan was given to 85 Turkish unrelated subjects. Concentrations of losartan and its carboxylic acid metabolite, E3174, were analysed by means of high-performance liquid chromatography in urine collected for 8 h. The CYP2C9 genotypes were determined in 85 subjects using polymerase chain reaction-based endonuclease digestion methods specific for CYP2C9*2 and *3. Losartan oxidation was also studied in vitro, using human CYP2C8 and CYP2C9 enzymes expressed in yeast.Results The frequencies of the allelic variants CYP2C9*2 and CYP2C9*3 were 0.100 and 0.088, respectively. The urinary losartan/E3174 ratio was significantly higher in subjects with CYP2C9*1/*3 genotype (median 2.35, n=12) than in subjects with CYP2C9*1/*1 (0.71, n=58) and *1/*2 (0.85, n=10) genotypes (P<0.05). In contrast to CYP2C9, no E3174 was formed by CYP2C8 in vitro.Conclusion The urinary losartan to E3174 metabolic ratio after a 25-mg losartan dose was found to be a safe and useful phenotyping assay for CYP2C9 activity in vivo. CYP2C9*3 variant allele is a major determinant of the enzyme activity, and it decreases losartan metabolism significantly, while CYP2C9*2 allele has less impact on enzyme function.     

Correlation between rhinometric measurement methods in healthy young adults

The most common rhinometric measurement methods used in modern rhinology are acoustic rhinometry, rhinomanometry, and nasal peak expiratory flow (PEF) rate. In this prospective study, we wanted to clarifiy whether the parameters given by these three methods in the same subject support each other and can be used simultaneously in clinical practice. We also wanted to define the dimensions of normal nasal geometry and function based on these three methods. The rhinometric measurements were done in 249 healthy white subjects consisting of 171 women and 78 men. The geometry was analyzed with regard to body mass index (BMI) and smoking habits. The result could he used as some kind of reference value for the same kind of patient cohort as when rhinological pathology is investigated. The measurements obtained by acoustic rhinometry showed only statistically significant correlations between the measured volume and minimal cross-sectional area in the nasal cavities (r = 0.959). Rhinomanometry showed only a statistically significant correlation between the measured resistance in expiration and inspiration (r = 0.977). Acoustic rhinometry, rhinomanometry, and nasal PEF did not show any correlations and the BMI did not have any effect on the results. Although the smoking group was relatively small in this cohort, the rhinometric methods showed smaller nasal cavity volume, higher resistance, and lower nasal PEF values. Based on these results, we recommend the use of these three rhinometric methods as independent instruments in rhinological examinations. However, in the pathological nose, e.g., smokers, the methods show equal changes in measurements. It is important to measure at least acoustic rhinometry and rhinomanometry at the same time in clinical practice to achieve good quality of examinations.     

Complications of Neodymium:YAG laser goniopuncture after deep sclerectomy

PURPOSE: To study the complications of Neodymium:YAG (Nd:YAG) goniopuncture after deep sclerectomy with collagen implant (DSCI). METHODS: All patients who underwent a Nd:YAG goniopuncture after a successful DSCI for primary open-angle glaucoma were included in a non-randomized clinical study. RESULTS: Nd:YAG goniopuncture was performed in 31 patients. The mean time from surgery to goniopuncture was 3.2 +/- 3.2 months. The mean intraocular pressure (IOP) before goniopuncture was 32.0 +/- 10.8 mmHg (SD); the mean IOP 1-2 hours after goniopuncture was 16.5 +/- 6.3 mmHg. After a mean follow-up of 5.4 +/- 2.8 months, the mean IOP was 17.8 +/- 11.6 mmHg. Three patients had a spontaneous iris prolapse after Nd:YAG goniopuncture and consequently high IOP. No signs of severe hypotension were observed. CONCLUSION: There are potentially serious complications relating to Nd:YAG goniopuncture after deep sclerectomy. However, further studies are needed to determine the safest time and level of IOP at which to perform Nd:YAG goniopuncture.