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Biomedical subjects

M Nagel

Publications and source records attributed to M Nagel.

At least 19 recordsLinked to original sources

Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.

Adult↗

Photoelectron spectroscopic investigations of chemical bonding in organically stabilized PbS nanocrystals.

The surface structure of organically capped PbS nanocrystals using synchrotron radiation excited core-level photoelectron spectroscopy has been studied. The nanocrystallites prepared by methods of colloidal chemistry have average diameters of 3.1, 3.9, 4.6, and 7.6 nm with narrow size distributions and are stabilized either with oleic acid only or with a combination of trioctylphosphine and oleic acid as ligands. High resolution photoelectron spectroscopy measurements allowed the surface structure to be studied and in particular how the organic ligands bind to the surface of the PbS nanocrystals to be elucidated. The results indicate that the trioctylphosphine ligands passivate only the surface S sites while oleic acid ligands appear to bind mainly to Pb sites.

Journal Article↗

Asynchronous optical sampling for high-speed characterization of integrated resonant terahertz sensors.

Two femtosecond Ti:sapphire lasers with slightly different repetition rates near 1 GHz are coupled to implement high-speed asynchronous optical sampling. The application of this technique is successfully demonstrated in the field of terahertz time-domain spectroscopy (TDS). A time delay of 1 ns is scanned at a frequency of 5 kHz without moving mechanical parts. Compared with that of conventional TDS schemes based on lock-in detection and moving mirrors, the readout time of integrated resonant THz sensors is reduced by a factor of 20, opening the way for high-throughput THz sensing in marker-free DNA analysis.

Journal Article↗

Signs of rapidly progressive dementia in a case of intravascular lymphomatosis.

Intravascular lymphomatosis (IVL), a rare type of non-Hodgkin's lymphoma, is an uncommon cause of progressive dementia, usually followed by death within a few months of onset of clinical disease. Often this aggressive tumor is only diagnosed at autopsy, because of misleading clinical features mimicking a broad spectrum of syndromes and the absence of circulating lympoma cells in the blood, bone marrow or cerebrospinal fluid in many cases. Here we present IVL in a 78-year-old woman with findings leading to the clinical diagnosis of vascular dementia with sudden beginning and positive 14-3-3 protein in the CSF, commonly reported in Creutzfeldt-Jakob disease (CJD).

14-3-3 Proteins↗

A functionalized THz sensor for marker-free DNA analysis.

We report on a novel resonant THz sensor for the label-free analysis of DNA molecules. The sensor allows the direct detection of DNA-probe molecules at functionalized electrodes via hybridization. Subsequent time resolved photoconductive sampling of the THz transmission identifies the binding state between probe and target DNA. Integrating neighbouring sensors on a chip, this technique can be extended to a parallel analysis of multiple DNA sequences. A clearly readable sensor response is obtained with less then 40 fmol of 20-mer single-stranded DNA molecules, indicating at least a sevenfold sensitivity increase compared to previous approaches.

Biosensing Techniques↗

The effect of transcranial magnetic stimulation over the cerebellum on the synkinesis of coordinated eye and head movements.

We made a study of coordinated saccadic eye and head movements following random and predictable horizontal visual targets by applying transcranial magnetic stimulation (TMS) over the cerebellum before the start of the gaze movement. We have found three effects of TMS on eye/head movements under these conditions. SACCADIC LATENCY-EFFECT: When stimulation took place shortly before movements commenced, significantly shorter latencies were found between target presentation and commencement of saccades: For predictable, to a lesser extent for random targets and TMS up to 75 ms before start of the saccade, latencies were significantly decreased when compared with no application of TMS. Without stimulation, latencies to random targets were within a range of 120-200 ms. EYE-HEAD INTERACTION-EFFECT: Without TMS, for amplitudes greater than 25 degrees, head movements usually preceded eye movements, as expected, especially for predictive responses. With the application of TMS shortly after the target display, the number of eye movements which preceded head movements, was significantly increased (p<0.001), and the delay between eye and head movements was reduced or reversed (p<0.001), compared with gaze movements without the use of TMS. SACCADIC PEAK VELOCITY-EFFECT: Applying transcranial magnetic stimulation at 5-25 ms after the position change of the 60 degrees target, and 50-5 s before the start of eye movement, mean peak velocity of synkinetic saccades increased up to 600 degrees/s, compared with 350-400 degrees/s without the use of TMS. We conclude that transient functional cerebellar deficits caused by the application of TMS can change the central synkinesis of eye-head coordination.

Adult↗

Label-free probing of genes by time-domain terahertz sensing.

A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a freespace analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed.

Binding Sites↗

Temporary cardiac asystolia induced by intraoperative irritation of the eighth right sided anterior cervical nerve root.

BACKGROUND: The 60 year old women with no prior history of arrhythmia or other cardiac symptoms was operated on for a cervical disc herniation at the level C7/D1. The C8 nerve root was visualized via a posterior approach. FINDINGS: Removal of the sequestrum and irritation of the anterior root with surgical instruments triggered cardiac arrest. INTERPRETATION: We offer the opinion that irritation of the anterior root led to diminished activity of the supraspinal sympathetic control system and consecutive hyper-activation of the parasympathetic system.

Cervical Vertebrae↗

Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats.

There is compelling evidence that withdrawal of neurotrophins can lead to impaired neuronal function and even apoptotic death of neurons. Recent experimental evidence suggests that antidepressant drugs and electroconvulsive treatment might work by enhancing CNS levels of neurotrophins. In addition, Lithium (LI) has been shown to exert robust neuroprotective effects apart from its well known mood-stabilizing effects in humans. In this study we investigated the effects of subchronic (14 days) treatment with various doses of LI on the NGF content of several regions of the adult rat brain. LI treatment, which resulted in prophylactic LI serum concentrations (0.72 +/- 0.08 mMol l(-1)), induced a significant (P < 0.05) increase in NGF concentrations in the frontal cortex (+23.2%), hippocampus (+72%), amygdala (+74%) and limbic forebrain (+46.7%) compared to untreated controls, whereas no effects on NGF concentrations were observed in the striatum, the hypothalamus or the midbrain, even using various LI doses. Moreover, no significant change in NGF concentrations in the frontal cortex was observed after acute (1 day) treatment with LI. Our findings lend support to the notion that an enhancement of NGF production may be specifically involved in the mechanisms of action of antibipolar treatments.

Animals↗

Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families.

Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifetime risk in gene carriers for synchronous and for metachronous colorectal cancer and endometrial cancer in women, prophylactic and extended surgery are considered as options for gene carriers. A 54-year-old patient with a history of metachronous rectal cancer and a family history fulfilling the Amsterdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histological examination of the specimen showed three synchronous colon carcinomas. The 31-year-old son carrying the pathogenic mutation refused to be included in the HNPCC surveillance program. One year later he presented with symptoms of bowel obstruction, and a carcinoma of the descending colon was diagnosed. Intraoperatively, in addition to the colon cancer, a small bowel cancer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented with synchronous cancer of the ascending colon and the lower rectum at the age of 49 years. Proctocolectomy and prophylactic hysterectomy were performed, which revealed an additional colon cancer and endometrial cancer. We discuss approaches for individual decision making for surgery in HNPCC patients. Is a subtotal colectomy indicated in the case of first colon cancer in HNPCC patients, or if the first tumor occurs in the lower rectum, should a proctocolectomy or a restorative proctocolectomy be considered? The aim of prospective clinical studies should be to assess acceptability, survival rates, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophylactic surgery.

Adult↗

[Secondary high-grade MALT lymphoma of the stomach in a 69-year-old patient with gastrocolic fistula].

A 69-year-old man was referred to our department with an exorbitant foetor ex ore, dysphagia and dyspepsia. Upper endoscopy had been performed prior by an outpatient gastroenterologist and the patient had received an eradication therapy for a Helicobacter pylori-induced gastritis. At admission upper endoscopy showed a gastric ulcer which drained a stinking fluid. Endosonography, computed tomography and an upper gastrointestinal series with water soluble media revealed a gastrocolic fistula. Multiple biopsies showed a low-grade gastric MALT lymphoma. Therefore, a surgical reconstruction with Roux-en-Y esophagojejunostomy and transverso-descendostomy was performed. The histology of the completely removed stomach revealed a high-grade Non Hodgkin Lymphoma (NHL) with parts of a low-grade NHL. 3 weeks after surgery chemotherapy was started with the CHOP-regime which was well-tolerated by the patient.

Aged↗

[Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma]

Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma. HISTORY AND CLINICAL FINDINGS: A 39-year-old woman was admitted to our department of gastroenterology with recurrent epigastrical pain. Ten years previously the diagnosis of von Hippel-Lindau (VHL)-syndrome has been established. Two years before a germ line mutation in exon 3 of the VHL-tumour suppressor gene has been detected. The patient has a healthy son with a normal VHL-gene and four healthy siblings who had refused a genetic blood test. INVESTIGATIONS: At abdominal ultrasound at the head of the pancreas three 4 2 cm large cysts and in the region of the left adrenal gland a 2,9 2,7 cm large tumor were visible. MRI of the abdomen revealed in addition a 2,2 1,5 cm large tumour of the right adrenal gland. An asymptomatic biadrenal phaeochromocytoma was detected by elevated urine catecholamines and 123I-MIBG-scintigraphy. TREATMENT AND COURSE: The cysts of the pancreas were punctured under endosonographical control and analysis of the cyst fluid was not suspicious of a malignant cystic tumour. The patient had no further abdominal complaints. After oral treatment with the alpha-blocker phentolamine the biadrenal phaeochromocytoma was treated by retroperitoneal laparoscopic surgery in an organ-sparing fashion. Postoperatively ACTH-stimulating test revealed a normal cortisol response. CONCLUSION: Adrenocortical function can be preserved by la-paroscopic adrenal-sparing surgery in bilateral phaeochromocytoma.

Journal Article↗

Transcranial magnetic stimulation over the cerebellum delays predictive head movements in the coordination of gaze.

We investigated coordinated saccadic eye and head movements following predictive horizontal visual targets at +/- 30 degrees by applying transcranial magnetic stimulation (TMS) over the cerebellum before the start of the gaze movement in 10 young subjects. We found three effects of TMS on eye-head movements: 1. Saccadic latency effect. When stimulation took place shortly before movements commenced (75-25 ms before), significantly shorter latencies were found between predictive target presentation and initiation of saccades. Eye latencies were significantly decreased by 45 ms on average, but head latencies were not. 2. Gaze amplitude effect. Without TMS, for the 60 degrees target amplitudes, head movements usually preceded eye movements, as expected (predictive gaze type 3). With TMS 5-75 ms before the gaze movement, the number of eye movements preceding head movements by 20-50 ms was significantly increased (p < 0.001) and the delay between eye and head movements was reversed (p < 0.001), i.e. we found eye-predictive gaze type 1. 3. Saccadic peak velocity effect. For TMS 5-25 s before the start of head movement, mean peak velocity of synkinetic eye saccades increased by 20-30% up to 600 degrees/s, compared to 350-400 degrees/s without TMS. We conclude that transient functional cerebellar deficits exerted by means of TMS can change the central synkinesis of eye-head coordination, including the preprogramming of the saccadic pulse and step of a coordinated gaze movement.

Adult↗

Clinical, endocrinological and radiography features in a child with McCune-Albright syndrome and pituitary adenoma.

McCune-Albright syndrome is a rare syndrome presenting with polyostotic dysplasia, cafe-au-lait spots and multiple endocrinopathies that is very often combined with precocious puberty. We examined the clinical, endocrinological and radiological features in a boy with McCune-Albright syndrome and pituitary adenoma. X-rays, magnetic resonance (MRI) scan, whole body scintigraphy, single photon emission computer tomography (SPECT) and 3D-reconstruction from bone SPECT was performed to evaluate clinical improvement after treatment with sandostatin and pamidronic acid. After a six-month period of treatment with sandostatin and pamidronate, bone scintigraphy revealed significantly reduced activity. Treatment with bromocriptine and methimazole led to normalization of prolactin and thyroid hormone levels. Mobility of the patient improved. A significant improvement as a result of treatment with sandostatin and pamidronic acid was found in this patient with generalized fibrous dysplasia. So far, this condition has been treated with pamidronate only in adults, but severely affected children also benefit from this treatment regimen.

Adenoma↗

[Serous cystadenoma of the pancreas].

INTRODUCTION: Serous cystadenomas of the pancreas are rare tumors and thought to be almost always benign. METHODS: We report our experience in the diagnosis and surgical treatment of 12 patients with these tumors. RESULTS: Between October 1993 and December 1998, 41 patients with cystic tumors of the pancreas underwent surgical resection; in 12 cases (11 women, 1 man) a serous cystadenoma (10 micro-cystic, 2 oligo-microcystic) was found. Only 6 (50%) patients had symptoms. The mean tumor size was 4.8 (2.7-10) cm. Ultrasound, CT and MRT usually could detect the mass, but differentiation with other cystic lesions was not reliable. All tumors were resected: 4 Whipple procedures, 7 distal pancreatectomies and 1 segmental resection were performed. No patient died after surgery and none had to be reoperated on. CONCLUSIONS: Because of the difficulty in reliably differentiating benign and malignant lesions of the pancreas, we believe that cystic tumors of the pancreas should be resected.

Adult↗

[Laparoscopic cholecystectomy in isolated gallbladder metastasis of malignant melanoma].

Metastasized malignant melanomas can affect all organs of the human body. However, isolated metastatic spreading into the gallbladder is rare. We treated two asymptomatic patients who had undergone primary curative resection of a melanoma. Gallbladder structures suggesting the presence of tumors were noticed in the follow-up investigations. The two patients underwent laparoscopic cholecystectomy to clarify their pathological relevance. Histologically, the tumor was a metastasis of the malignant melanoma in each case. Surgery is indicated in stage IV in isolated metastatic spreading to the gallbladder in order to avoid symptoms or tumor complications. Since the vast majority of melanoma metastases of the gallbladder are located intraluminally and lymphadenectomy in the region of the hepatoduodenal ligament does not appear to be appropriate, the operation should be carried out laparoscopically. The value of postadjuvant chemoimmunotherapy after metastasis resection is being investigated in numerous studies at present.

Aged↗