Elfriede Fritzer

MRI and FDG-PET in the assessment of inflammatory aortic arch syndrome in complicated courses of giant cell arteritis

Objectives: To evaluate the use of MRI and FDG-PET for the diagnosis and measurement of disease activity of inflammatory aortic arch syndrome in patients with complicated giant cell arteritis. Methods: MRI and FDG-PET were performed for 25 patients with giant cell arteritis who presented with a complicated disease course despite immunosuppressive therapy. Disease activity of the thoracic aorta and the supra-aortic arteries as assessed by both modalities was compared with serological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and clinical findings (Birmingham vasculitis activity score (BVAS.2)). Additionally, the usefulness of MRI for assessment of vessel wall thickening, aneurysms and stenoses was evaluated. Results: In 17/25 patients, MRI disclosed structural vessel lesions suspicious for vasculitis. Active disease was detected by MRI, thoracic PET, and whole body PET in 22, 14 and 20 patients, respectively. While serological and clinical findings correlated significantly with each other, there was no concordance with MRI and only low, non-significant correlation of PET with CRP (rs =  −0.158, 0.136), ESR (rs =  −0.232, 0.320) and BVAS.2 (rs =  −0.064, 0.221) for disease activity. Conclusions: MRI and PET are unreliable for assessing large-vessel inflammation in patients with giant cell arteritis and pre-existing immunosuppressive therapy. MRI is valuable for its ability to detect morphological vessel lesions, such as aneurysms and stenoses.

Biochemical tissue-specific injury markers of the heart and brain in postpartum cord blood

OBJECTIVE We sought to establish references ranges and to test the hypothesis that biochemical tissue-specific markers for the heart in umbilical cord blood of newborns with cardiac defects and intrauterine growth restriction (IUGR) are abnormal. STUDY DESIGN A prospective study was conducted. Serum samples of the umbilical vein (n = 280) and artery (n = 156) from 599 healthy newborns at 37(+0)-42(+0) weeks of gestation were collected. Total creatine kinase (CK), CK-MB heart type (CK-MB), cardiac troponin T (cTnT), myoglobin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and S100 were measured. Reference ranges for each marker were constructed. Concentrations of tissue-specific markers from umbilical cord blood of neonates with cardiac defects (n = 10) and IUGR (n = 41) were plotted against the established reference ranges. RESULTS Reference ranges for each studied marker were established for both umbilical artery and vein. In fetuses with cardiac defects, both NT-proBNP (4/6 [66%] in the artery, 7/10 [70%] in the vein) and cTnT (2/10 [20%] in the vein) were increased. In fetuses with IUGR in the vein, NT-proBNP (10/41 [24%]) and cTnT (5/41 [12%]) were increased, whereas S100 (9/41 [21%]) was decreased. CONCLUSION In a subset of neonates with cardiac defects or growth restriction, irrespective of the pH at birth, tissue-specific injury markers for the heart in umbilical cord blood are abnormal.

X chromosomal variation is associated with slow progression to AIDS in HIV-1-infected women

AIDS has changed from a mostly male-specific health problem to one that predominantly affects females. Although sex differences in HIV-1 susceptibility are beyond doubt, the extent to which sex affects the onset and progression of AIDS has remained elusive. Here, we provide evidence for an influence of X chromosomal variation on the course of retroviral infection, both in HIV-1-infected patients and in the rhesus macaque model of AIDS. A two-stage, microsatellite-based GWAS of SIV-infected monkeys revealed MHC class I markers and a hitherto-unknown X chromosomal locus as being associated with a nominal score measuring progression to AIDS (Fishers exact p < 10(-6)). The X chromosomal association was subsequently confirmed in HIV-1-infected patients with published SNP genotype data. SNP rs5968255, located at human Xq21.1 in a conserved sequence element near the RPS6KA6 and CYLC1 genes, was identified as a significant genetic determinant of disease progression in females (ANOVA p = 8.8 x 10(-5)), but not in males (p = 0.19). Heterozygous female carriers of the C allele showed significantly slower CD4 cell decline and a lower viral load at set point than TT homozygous females and than males. Inspection of HapMap revealed that the CT genotype is significantly more frequent among Asians than among Europeans or Africans. Our results suggest that, in addition to the individual innate and adaptive immunity status, sex-linked genetic variation impacts upon the rate of progression to AIDS. Elucidating the mechanisms underlying this sex-specific effect will promote the development of antiretroviral therapies with high efficacy in both sexes.

Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a German multicenter study.

Objective: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum biochemistry using free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. Methods: This was a multicenter study of screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum free β-hCG and PAPP-A at 11-14 weeks of gestation, using the methodology developed by the Fetal Medicine Foundation. The distribution of estimated risks for trisomy 21 was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 were calculated. Results: In total, 3864 singleton pregnancies with live fetuses at 11-14 weeks were examined and the fetal NT and maternal serum free β-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 33 (range 15-46) years and, in 1271 (35.8%), the age was 35 years or more, the median gestation at screening was 12 (11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The fetal NT was above the 95th centile in 73.7% (14 of 19) of trisomy 21 and in 4.8% (169 of 3505) of normal pregnancies. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free β-hCG and PAPP-A was 1 in 300 or greater in 6.6% (233 of 3505) of normal pregnancies, in 84.2% (16 of 19) of those with trisomy 21 and 88.9% (24 of 27) of those with other chromosomal defects. Conclusions: In Germany, the results of screening for chromosomal defects by measurement of fetal NT and maternal serum biochemistry, in centers with appropriately qualified sonographers, are similar to those reported in the UK using the same methodology.

Reconstruction of the lower lip: rationale to preserve the aesthetic units of the face.

Background: The boundaries of the aesthetic units of the face are often crossed after lower lip cancer surgery. The aim of this study was to compare the aesthetic and functional outcome after use of different operative techniques based on the concept of the aesthetic units of the face. Materials: Sixty-three patients were evaluated after lower lip reconstruction. The aesthetic outcome was recorded by standard photography evaluating the disruption of the boundaries of the aesthetic units of the face, lip projection, and the resulting facial expression. The functional outcome consisted of the evaluation of mouth opening, pouting, and lips at rest for the evaluation of mouth continence. Three techniques were used: wedge excision, the Webster-Fries method, and the step technique. The step technique was combined with an Abbé or an Estlander flap in defects involving more than two-thirds of the lip. Results: In defects involving up to one-third of the lip, the aesthetic outcome was better for the step technique than for wedge excision (a statistical trend was observed, p = 0.088). In defects involving two-thirds of the lip, the aesthetic and functional outcome was better using the step technique than the Webster-Fries method (p = 0.002), because the boundaries of the aesthetic units are respected. In defects involving more than two-thirds of the lip, the result was better using the step technique combined with the Abbé flap. Conclusion: The authors have shown that the step technique alone or combined with a flap of the opposite lip is a rational approach for preserving the aesthetic units of the face and its function.

Somatosensory processing in a German family with PINK1 mutations: its potential role in Parkinson disease

Background: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia. Objective: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. Methods: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). Results: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. Conclusions: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.

Somatosensory function in asymptomatic Parkin‐mutation carriers

Background and purpose:  It is a matter of debate whether somatosensory abnormalities in Parkinson’s disease (PD) precede or follow PD motor signs and whether they are of central or peripheral origin. The sensory sural nerve action potential amplitude (SNAP) was previously reported to be reduced in symptomatic Parkin‐associated PD. The aim of our study was to investigate asymptomatic Parkin‐mutation carriers to elucidate whether putative somatosensory abnormalities precede motor symptoms therewith helping to determine the origin of somatosensory signs.

Hepatic aminotransferases of normal and IUGR fetuses in cord blood at birth

BACKGROUND The accepted standard for assessing the wellbeing of the newborn is the Apgar score and blood gas analysis. However, the prediction of neonatal morbidity or mortality is limited. In small-for-gestation (SGA) fetuses at 18-38 weeks of gestation, pO(2) is <5th centile both in the umbilical artery and vein in 30%. In a previous study in singleton term neonates cardiac specific enzymes (B-type natriuretic peptide, BNP and cardiac troponin T, cTnT) are increased in growth-restricted fetuses compared with normals. AIMS To test the hypothesis, that fetuses with intra uterine growth restriction (IUGR) have elevated AST (GOT) and ALT (GPT) aminotransferases as a result of hypoxic liver cell injury, and to establish references ranges. STUDY DESIGN Prospective cohort study, serum of umbilical artery (n=156) and vein (n=180), 599 normal singletons at 37(+0)-42(+0)weeks, neonates with IUGR (n=41), analysis for pH, birthweight and maternal weight, spontaneous vs cesarean section, vein vs artery and for the sex. OUTCOME MEASURES Aspartate aminotransferase (AST, GOT) and Alanine aminotransferase (ALT, GPT) were measured in normals and IUGR neonates. RESULTS Neonates with IUGR (n=41) had AST values that were not different from the reference group, but had significantly lower ALT (-1.49, 95% CI -1.98 to -1.00 vs 0.14, 95% CI -0.42-0.13), (p<0.001), (Fig. 3). CONCLUSIONS In neonates with IUGR, hypoxic hepatic injury markers in cord blood were not elevated. Rather, a substantially reduced ALT suggests a down-regulated hepatic activity.

High white blood cell count in patients with giant cell arteritis predicts an increased risk of stenosis in upper extremity arteries

Stenosis of the arteries of the upper extremities occurs in 13–29% of patients with giant cell arteritis (GCA).1,–,3 Endovascular therapy has been reported to be successful, especially prior to extensive vessel obstruction.4 Until now, no predictive parameter is known for the early identification of persons at risk of ischaemic disease of the upper limbs. Therefore, we retrospectively analysed laboratory markers of inflammation in 105 patients (86 women, mean age 65.2 years) from a tertiary rheumatological care centre with a clinical diagnosis of GCA. Fulfilment of the American College of Rheumatology criteria was required, except for patients with typical stenosis of the arm arteries, older than 50 years of age at disease onset.5 6 Laboratory findings were obtained from the primary care physician or the medical centre consulted at disease onset, preceding anti-inflammatory …

Single Mandibular Implant Study: Recruitment Considerations.

PURPOSE The aim of this multicenter single mandibular implant study was to compare the clinical outcome of an immediately loaded implant placed in the midline of an edentulous mandible with the clinical outcome when closed healing and delayed loading is chosen. Here, the patient recruitment period and the main reasons for exclusion were analyzed. MATERIALS AND METHODS Patient recruitment was performed at nine German universities. Rather conservative inclusion and exclusion criteria, including denture satisfaction, denture status, a psychologic symptom checklist, and a defined bone height in the posterior mandible, had to be fulfilled. It was initially calculated that 230 persons would have to be screened within 13 months to include 180 persons in the trial. RESULTS Within 13 months (December 2012 to December 2013), 201 patients were screened for possible inclusion in the trial and 148 met the inclusion criteria. Finally, after the recruitment period was extended by 2.5 months, 224 patients were screened and 169 were included. Of those screened, 55 (24.6%) did not meet the inclusion criteria and were excluded. Another 4 patients (1.8%) were excluded based on their psychologic symptom checklist score, while 5 others (2.8%) showed signs of noncompliance. A further 8 patients (4.4%) decided not to participate and withdrew their informed consent, and another 3 (1.3%) were no longer available after screening. Another 2 patients were excluded due to medical contraindications and 1 due to an insufficient mandibular denture. In 34 cases (15.2%), the residual bone height did not comply with McGarry type II or III. CONCLUSION Within the limitations of this patient recruitment period, it can be concluded that residual bone height is the most important factor when considering elderly edentulous patients for implant therapy. The psychologic symptom checklist score was less important.