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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 37 records · Page 2Linked to original sources
PubMed2003

IDDM2/insulin VNTR modifies risk conferred by IDDM1/HLA for development of Type 1 diabetes and associated autoimmunity.

AIM/HYPOTHESIS: Type 1 diabetes (T1D) is an autoimmune disease with multiple susceptibility genes. The aim of this study was to determine whether combining IDDM1/HLA and IDDM2/ insulin( INS) 5' variable number of tandem repeat locus (VNTR) genotypes improves T1D risk assessment. METHODS: Patients with T1D (n=488), control subjects (n=846), and offspring of parents with T1D (n=1122) were IDDM1 and IDDM2 genotyped. Offspring were followed for islet autoantibodies and T1D from birth until the age of 2 to 12 years. RESULTS: Compared to the I/I INS VNTR genotype, the I/III and III/III genotypes reduced T1D risk conferred by IDDM1/HLA in all HLA genotype categories of the case-control cohort by 1.6-fold to three-fold. The highest T1D risk was associated with INS VNTR class I/I plus HLA DR3/DR4-DQ8 (20.4% in patients, 0.6% in control subjects) or HLA DR4-DQ8/DR4-DQ8 (6.3% in patients, 0.2% in control subjects). In the offspring, HLA DR3/DR4-DQ8 and DR4-DQ8/DR4-DQ8 conferred increased risk for early development of islet autoantibodies (14.6% and 12.9% by age 2 years). Offspring with these high risk IDDM1 genotypes plus the INS VNTR class I/I genotype (n=71; 6.3%) had the highest risk of developing islet autoantibodies (21.8% by age 2 years vs 8.9% in offspring with high risk IDDM1 plus INS VNTR class I/III or III/III genotypes, p<0.05) and T1D (8.5% by age 6 years vs 4.3%). Offspring who developed autoantibodies to multiple antigens had increased frequencies of both high risk IDDM1 and IDDM2 genotypes (p<0.0001), whereas offspring who developed autoantibodies to GAD only had increased frequencies of high risk IDDM1 and protective IDDM2 genotypes, suggesting that IDDM2 influences the autoimmune target specificity. CONCLUSION/INTERPRETATION: Combining IDDM1 and IDDM2 genotyping identifies a minority of children with an increased T1D risk.

Autoantibodies↗
PubMed2003

Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain.

The cannabinoid receptor one (CB1) is responsible for the effects of cannabis on motor and cognitive function in the CNS. There is to date very limited information about the CB1 gene expression in the human brain, in particular during fetal development. In the present study, in situ hybridization experiments were used to examine the microscopic and macroscopic organization of the CB1 mRNA expression in normal human fetal (approximately 20 weeks of development) and adult brains. The fetal brain showed a distinct heterogeneous pattern of the CB1 mRNA expression which was low to moderate in many brain areas. The most striking feature of the fetal brain was the intense expression in the hippocampal CA region and basal nuclear group of the amygdaloid complex. Many of the same brain areas that showed positive expression of the CB1 mRNA in the fetal brain also expressed the gene in the adult brain. However, aside from an intense expression in the hippocampus which resembled that in fetal brain, the adult brain showed very high expression throughout the cerebral cortex, caudate nucleus, putamen and cerebellar cortex. These results document a different pattern of the anatomical organization of the CB1 mRNA expression in the mid-gestation fetal and adult human brain. Overall, the high CB1 mRNA expression in the fetal hippocampus and amygdala indicates that these limbic structures might be most vulnerable to prenatal cannabis exposure.

Adolescent↗
PubMed2003

Transcranial oximetry using fast near infrared spectroscopy can detect failure of collateral blood supply in humans.

We tested the hypothesis that transcranial oximetry by fast scanning near infrared spectroscopy can detect local desaturation of hemoglobin in arterial vessels of cerebral circulation with impaired blood supply. A total of 74 near infrared spectroscopy recordings were taken from the intact skull of humans. Perfusion of the hemisphere under the detector was assessed in one of four groups: (1) healthy volunteer; (2) patient, unaffected side; (3) patient, affected side with intact collateral blood supply; (4) patient, affected side, impaired collateral blood supply. Transcranial saturation was 0.90+/-0.01 (all values reported as mean+/-S.E.) in healthy volunteers (n=24), 0.92+/-0.008 in the unaffected hemisphere of patients (n=23), 0.92+/-0.001 in the affected side if collateral supply with blood was intact (n=16). There was no statistical significance between these groups. Saturation in affected hemispheres with impaired collateral blood supply (n=9) was 0.81+/-0.028, which was significantly different from all other groups (P<0.05, one way-ANOVA). We conclude, that transcranial pulse oximetry can detect local hypoxia if collateral blood supply fails.

Cerebrovascular Circulation↗
PubMed2003

Root resorption in dental trauma: 45 cases followed for 5 years.

We aimed to: (i) study the prevalence of root resorption after luxation or avulsion injuries on permanent teeth referred to our dental clinic over a 3-year period; (ii) study the relationship between type of injury and resultant type of resorption complication; and (iii) evaluate success of treatment protocols for various resorption complications. We observed 1943 patients with dental trauma, aged between 2 and 26 years, referred to the Accident and Emergency Department of the Dental Clinic, University of Brescia, from 1st September 1997 to 31st December 2001. Of these, 261 permanent teeth had sustained luxation (n = 188) or avulsion (n = 73) injuries. Permanent teeth luxation and avulsion injuries occurred most often in upper incisors (75%) of patients mostly aged 12-21 years, with males more commonly affected than females (68.3% vs. 31.7%). These cases were followed for 5 years, and complications and response to treatment were recorded. Root resorption was observed in 45 (17.24%) of these cases. Of the 45 cases with resorption, 9 were associated with luxation injury (20%) while 36 (80%) with avulsion. We distinguished 30 cases of inflammatory root resorption (18 transient and 12 progressive) and 15 cases of ankylosis and osseous replacement. When resorption was recognized, quick and effective treatment could still result in an excellent functional and aesthetic outcome for these teeth.

Adolescent↗
PubMed2003

The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data.

OBJECTIVE: The soluble leptin receptor (sOB-R) was recently identified as the main leptin-binding protein in human blood. The aim of our study was to elucidate the effects of physiologically relevant amounts of sOB-R on leptin-induced proliferation in a cell model. SUBJECTS AND MEASUREMENTS: To determine molar ratios between sOB-R and leptin in vivo, we measured both parameters in the serum of 529 healthy children and adolescents. For our in vitro cell model, mouse pre-B cells, transfected with the long form of the murine leptin receptor (BAF3/L46), were incubated with recombinant human leptin at two different basal levels (0.5 and 0.1 nM) and with the sOB-R at varying levels. The proliferative response of the cells was quantified by a (3)H-thymidine uptake assay. RESULTS: Significantly higher molar sOB-R/leptin ratios were observed during the first years of life, up to a 7.67-fold excess of sOB-R (quartiles: 4.43/10.27) in boys, compared to the states of prepuberty and puberty. An up to 10-fold molar excess of the sOB-R, reflecting the in vivo situation, resulted in a significant suppression of leptin action in the cell model. In contrast, gradually decreasing ratios of lower than two, as calculated during the progression of childhood and in early puberty, corresponded to proliferative rates in vitro as determined at basal leptin concentrations. CONCLUSION: At a distinct molar excess, sOB-R may suppress leptin action through inhibition of specific leptin binding to membrane-bound receptors in vitro. In vivo, sOB-R may further function to delay leptin clearance and increase the available leptin pool in the circulation. In the case of a massive excess of sOB-R, is it likely to be inhibitory to leptin interaction with the tissue membrane-bound OB-R.

Adolescent↗
PubMed2003

[Evolution of inflammatory parameters after fibroid embolization].

PURPOSE: To describe the rise of classical laboratory tests for inflammation following transarterial uterine fibroid embolization (UFE) in order to monitor the normal course following UFE. MATERIALS AND METHODS: In 20 females, white blood cell (WBC) count and C-reactive protein (CRP) were determined before and up to 5 days after UFE. With the exception of one noninflammatory complication, the post-procedure course was uneventful in all patients. The measured values were correlated with both the total uterine volume and the amount of instilled embolizing agent. RESULTS: Following UFE, an increase in the WBC count to an average maximum of 10.8 +/- 3.5/wL (range 5.9 - 18.6/wL) was found. In 13 of 20 patients, the WBC count was above normal on at least one day following UFE. The increase reached the maximum on the third post-interventional day and subsided within 5 days after the UFE. The CRP values increased significantly to an average maximum of 41.9 +/- 28.8 mg/l. The maximum was found on the 2nd post-interventional day in 8 patients, on the 3rd day in 11 patients and on the 4th day in one patient. No correlation to the total uterine volume or to the amount of the instilled embolizing agents was detected. CONCLUSION: Following uncomplicated UFE, a steep increase in CRP occurs with no or only a mild increase in the WBC count, which does not indicate an infected fibroid. The maximum is reached on the 3rd or 4th post-interventional day, followed by a decline in CRP and normalization of the WBC count.

Adult↗
PubMed2003

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.

Adolescent↗
PubMed2002

[Obesity in children and adolescents in Germany. Significant and persistent increase of prevalence. Appeal to treatment].

In Germany, the number of overweight children and adolescents is increasing. The increase in the prevalence of obesity shows considerable regional differences. Related to recent German reference data with an expected prevalence of 3%, we find today in some regions a prevalence of 7% in 5- to 6-year-olds and 8% in 13- to 15-year-olds. While the reasons for this development are not fully clear, it may be assumed that the increase in physical inactivity, together with the ready availability of an abundance of high-energy foods are significant contributing factors. A large percentage of children and adolescents suffering from obesity also have considerable co-morbidity. It is to be expected that this will in the future considerably increase the financial burden on public health care and society as a whole. Effective prevention and therapeutic countermeasures are necessary to deal with this problem.

Adolescent↗
PubMed2002

[Ever more children and adolescents are overweight. How can the obesity epidemic be stopped?].

In Germany, the number of overweight children and adolescents is increasing. The increase in the prevalence of obesity shows considerable regional differences. Related to recent German reference data with an expected prevalence of 3%, we find today in some regions a prevalence of 7% in 5- to 6-year-olds and 8% in 13- to 15-year-olds. While the reasons for this development are not fully clear, it may be assumed that the increase in physical inactivity, together with the ready availability of an abundance of high-energy foods are significant contributing factors. A large percentage of children and adolescents suffering from obesity also have considerable co-morbidity. It is to be expected that this will in the future considerably increase the financial burden on public health care and society as a whole. Effective prevention and therapeutic countermeasures are necessary to deal with this problem.

Adolescent↗
PubMed2002

Intensive care management of patients with severe intracerebral haemorrhage after endovascular treatment of brain arteriovenous malformations.

We studied the impact of emergency neurosurgery and intensive care on the outcome for patients with severe intracerebral haemorrhage after endovascular treatment of brain arteriovenous malformations (AVMs). We reviewed the case notes of 18 patients with severe haemorrhage after embolisation of a brain AVM between 1986 and 2001. During this period the treatment changed: before 1993, these patients were not surgically treated, and they died, while after 1994, all patients underwent emergency surgery. We established a standardised protocol for emergency treatment and intensive care in May 1998, and emergency surgery was performed as soon as possible after the onset of symptoms of haemorrhage. Postoperative intensive care was according to a standardised regime. During these 15 years, 24 out of 605 patients undergoing 1066 interventions had a haemorrhage during or after the procedure, of which 18 were severe (3% of patients, 1.7% of interventions). All patients had a severe clinical deficit (mean Glasgow coma scale 4.2); eight had uni- or bilateral mydriasis. From 1989 to April 1998 four (31%) of 13 patients died, one (7.5%) remained in a vegetative state and eight (61.5%) made a good recovery. All five patients treated between 1998 and 2001 had a favourable outcome. The mean time from onset of the symptoms of haemorrhage to reaching the operation room was 129 min between 1989 and 1998 and 24 min between 1998 and 2001. Standardised emergency treatment and intensive care with early resuscitation, minimal radiological exploration before rapid surgery improved the outcome. A short time between the onset of the symptoms of haemorrhage and evacuation of the haematoma may be the most important factor for a favourable outcome.

Adult↗
PubMed2002

Neurological and neuropsychological outcome after SAH.

The fact that neurological status and physical integrity alone do not sufficiently assess the overall state of patients after aneurysmal subarachnoid hemorrhage (SAH) gives rise to the necessity for complementary neuropsychological investigation. Neuropsychological work-up should also cover an emotional state, psychosocial adjustment and competence in everyday life of the patients. In our prospective study we investigated 82 patients three months and one year after SAH and early clipping of the aneurysm. For the evaluation of postoperative neurological functions the Glasgow Outcome Scale (GOS) was used. For the neuropsychological assessment we used standardized measures of verbal and figural learning and memory, verbal and figural fluency, speed of information processing, visuospacial abilities and affective function. One year after SAH 95.6% of patients with Hunt&Hess Grade 1 and 2 on admission showed good neurological results (GOS 4 and 5). However, only 30.1% (18 of 63 patients with a favourable neurological outcome--GOS 4 and 5) did not show any neuropsychological deficit. Localization of the ruptured aneurysm significantly correlated with cognitive measures. The best cognitive outcome was shown in patients with aneurysms on the anterior communicating artery (ACoA) followed by posterior communicating artery (PCoA) and those located on the internal carotid artery (ICA) on the right side.

Aneurysm, Ruptured↗
PubMed2002

New methods for monitoring cerebral oxygenation and hemodynamics in patients with subarachnoid hemorrhage.

Radiographic cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) do not reflect cerebral hemodynamics and oxygenation and may occur in the absence of clinical deficit and vice-versa. This report is to describe preliminary findings in further development of a non invasive method to estimate regional cerebral oxygenation and perfusion. Measurements were performed with a technique combining near infrared spectroscopy (NIRS) and indocyaningreen (ICG) dye dilution. Successful data analysis has been performed based on the decomposition in pulsatile and non-pulsatile components of NIRS absorption data collected before and during the passage of ICG through the vascular bed under the NIRS-detector. First measurements in patients with CVS suggest that the technique could become a powerful tool in the detection and treatment of CVS. This non invasive technique can be done at the bedside, it seems to be safe, easy to perform and less time-consuming compared to conventional techniques. The influence of extracerebral bone and surface tissue on cerebral NIRS signal has not been clarified yet. Therefore a new subdural NIRS probe has been developed, which gives the opportunity to measure directly the concentration of the chromophores in the brain without the influence of extracerebral contamination. In future comparative measurements with conventional NIRS probes on the scalp will allow to quantify and eliminate extracerebral contamination from the NIRS signal.

Adult↗
PubMed2002

Perfusion and molecular diffusion-weighted MR imaging of the brain: in vivo assessment of tissue alteration in cerebral ischemia.

The combined use of perfusion imaging (PI) and diffusion-weighted imaging (DWI) is opening a new window into the processes that occur during the first hours of ischemia. DWI detects changes in molecular diffusion associated with cytotoxic edema. PI characterizes the degree of regional hypoperfusion. Regions showing mismatches between DWI and PI, i.e. hypoperfused areas with normal diffusion behavior are considered potentially salvageable. We present results of 11 patients with an occlusion of the middle cerebral artery stem and spontaneous stroke evolution. Whereas the infarct was clearly visible on initial DWI and PI, surrounding tissue at risk of infarction was marked in all patients by an increased blood volume and transit time, but only in a subgroup (n = 3) where alteration were more pronounced this tissue at risk was progressively infarcted. These human DWI and PI data show alterations in the area of tissue at risk which correlates with infarct progression.

Adolescent↗
PubMed2002

Clinical and epidemiological study of traumatic root fractures.

The aim of this work was to study the prevalence and clinical presentation of root fractures in a series of patients with dental trauma. Treatment strategies were classified and outcomes after a 6-month period presented. The study population comprised 76 patients (between the ages of 2 and 55 years) with 93 root fractures in their teeth (18 primary, 75 permanent). Data were collected following the taking of a detailed clinical history, objective clinical examination and photographic and radiological investigation. Since most of the primary teeth were extracted, only cases with root fracture of permanent teeth were followed-up: in all, 24 patients with 31 teeth with root fractures. The prevalence of root fractures in permanent teeth was 7.7% of all injuries, while in primary teeth it was 3.8%. The most frequently involved teeth were the maxillary incisors with a percentage of 75% in permanent teeth. Moreover, 40% of root fractures in permanent teeth were associated with fracture of the alveolar bone and of the soft tissues and in 45% of cases, the adjacent teeth were also injured. The results of this study reaffirm the necessity for scrupulous diagnosis of teeth after a traumatic injury. Adjacent teeth and those in the opposing arch should not be ignored. Treatment is multidisciplinary, requiring surgical, orthodontic, operative and prosthetic compliance. Periodic check-up is essential.

Adolescent↗
PubMed2002

[1H-MR Spectroscopy of brain tumors in the course of radiation therapy: Use of fast spectroscopic imaging and single-voxel spectroscopy for diagnosing recurrence].

PURPOSE: To improve differential diagnosis of residual or recurrent tumor vs. tissue necrosis in the course of radiation therapy of neurosurgically-treated brain tumors by application of fast (1)H-MR spectroscopic imaging in combination with single-voxel spectroscopy (SVS). METHODS: 54 patients after with malignant brain tumor (44 cases of glioblastoma, 10 other high-grade gliomas) were examined post-surgically in a total of 140 proton MRS examinations in the course of radiotherapy and in follow-up controls. Fast SI acquisition was performed as single-slice or double-slice TSI sequence with 32 x 32 phase encodings within 11 or 15 minutes, respectively. SVS with TR/TE 2000/272 ms yielded relative metabolite ratios, and in 15 patients the time courses of the absolute concentrations of brain metabolites were also determined. RESULTS: In the group of 44 patients that could be tracked by MRS until therapy completion, TSI localized in 23 patients a persistent or newly arisen distinct choline accumulation indicating residual or recurrent tumor after radiation therapy. In all these cases MRS diagnosis was confirmed histologically or by short-term follow-up. However, in 6 of 15 patients showing a normal choline pattern in the TSI acquisition, tumor recurrence appeared within three months. SVS provided early recognition of recurrent tumor when detecting characteristic alterations of metabolite concentrations oin therapy follow-up. CONCLUSION: TSI and SVS represent complementary MRS techniques and are able to diagnose tumor recurrence early and unambiguously in cases where focal choline accumulation is detected.

Adult↗
PubMed2002

Three-dimensional magnetic resonance cholangiopancreatography with respiratory triggering in the diagnosis of primary sclerosing cholangitis: comparison with endoscopic retrograde cholangiography.

BACKGROUND AND STUDY AIMS: The purpose of this study was to evaluate the accuracy of respiratory-triggered three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) for the detection of primary sclerosing cholangitis (PSC) and to compare the specific findings of magnetic resonance cholangiography and endoscopic retrograde cholangiography in patients with PSC. PATIENTS AND METHODS: The MRCP findings were evaluated in 150 patients with clinical symptoms (progressive fatigue, pruritus followed by icterus) and/or elevated values for alkaline phosphatase and serum aspartate transaminase, and occasionally an elevated serum concentration of bilirubin as a sign of cholestasis, who were consecutively referred for magnetic resonance imaging. Two observers independently classified bile duct abnormalities and established the MRCP diagnosis in a consensus reading. The results of MRCP were compared with the definitive diagnosis, which was based on the clinical history and laboratory and histological data, as well as on endoscopic retrograde cholangio-pancreatography (ERCP) findings. In a second step, the observers compared the delineation of the biliary system and morphological findings using MRCP and ERCP in patients with confirmed PSC. RESULTS: Diagnostic examinations were obtained in 146 of the 150 MRCPs (97 %). The diagnosis of PSC was confirmed by clinical data and ERCP in 34 of these 150 patients (23 %). The sensitivity and specificity of MRCP for diagnosing PSC were 88 % (29 of 33) and 99 % (108 of 109), respectively. MRCP and ERCP yielded similar scores for the delineation of the biliary system (P = 0.2) in patients with PSC. However, different bile duct abnormalities leading to the diagnosis of PSC were depicted by MRCP and ERCP; more bile duct stenoses and pruning were seen with ERCP and more skip dilatation with MRCP (P < 10(-4)). CONCLUSION: In patients with PSC, MRCP is a highly sensitive method and its diagnostic accuracy is comparable to that of ERCP.

Adolescent↗
PubMed2002

Short-term growth response to GH treatment and considerations upon the limits of short-term growth predictions.

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.

Anthropometry↗