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Biomedical subjects

G Mack

Publications and source records attributed to G Mack.

At least 19 recordsLinked to original sources

Corrections to universal fluctuations in correlated systems: the two-dimensional XY model.

Generalized universality, as recently proposed, postulates a universal non-Gaussian form of the probability density function (PDF) of certain global observables for a wide class of highly correlated systems of finite volume N. Studying the two-dimensional XY model, we link its validity to renormalization group properties. It would be valid if there were a single dimension 0 operator, but the actual existence of several such operators leads to T-dependent corrections. The PDF is the Fourier transform of the partition function Z(q) of an auxiliary theory which differs by a dimension 0 perturbation with a very small imaginary coefficient iq/N from a theory which is asymptotically free in the infrared. We compute the PDF from a systematic loop expansion of ln Z(q).

Journal Article↗

Quality assurance in stereotactic radiosurgery/radiotherapy according to DIN 6875-1.

The new DIN ('Deutsche Industrie-Norm') 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 +/- 0.0086, 0.9578 +/- 0.0057 and 0.8741 +/- 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 +/- 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.

Quality Control↗

Analyzing 3-tesla magnetic resonance imaging units for implementation in radiosurgery.

OBJECT: The limiting factor affecting accuracy during gamma knife surgery is image quality. The new generation of magnetic resonance (MR) imaging units with field strength up to 3 teslas promise superior image quality for anatomical resolution and contrast. There are, however, questions about chemical shifts or susceptibility effects, which are the subject of this paper. METHODS: The 3-tesla MR imaging unit (Siemens Trio) was analyzed and compared with a 1-tesla unit (Siemens Magnetom Expert) and to a 1.5-tesla unit (Philips Gyroscan). Evaluation of the magnitude of error was performed within transverse slices in two orientations (axial/coronal) by using a cylindrical phantom with an embedded grid. Deviations were determined for 21 targets in a slab phantom with known geometrical positions within the stereotactic frame. Distortions caused by chemical shift and/or susceptibility effects were analyzed in a head phantom. Inhouse software was used for data analyses. The mean deviation was less than 0.3 mm in axial and less than 0.4 mm in coronal orientations. For the known targets the maximum deviation was 1.16 mm. By optimizing these parameters in the protocol these inaccuracies could be reduced to less than 1.1 mm. Due to inhomogeneities a shift in the z direction of up to 1.5 mm was observed for a dataset, which was shown to be compressed by 1.2 mm. CONCLUSIONS: The 3-tesla imaging unit showed superior anatomical contrast and resolution in comparison with the established 1-tesla and 1.5-tesla units; however, due to the high field strength the field within the head coil is very sensitive to inhomogeneities and therefore 3-tesla imaging data will have be handled with care.

Equipment Design↗

[Multifocal electroretinogram for assessing sun damage following the solar eclipse of 11 August 1999].

Following the eclipse of 11 August 1999, the ophthalmological clinic of Strasbourg cared for 4 patients who suffered from sun damage. The multifocal electroretinogram (ERG) carried out on our first patient enabled us to not only confirm the existence of a residual maculopathy as shown by the static visual field, but also, and above all to quantify the foveolar deficit. Moreover, with the other 3 patients, the multifocal ERG enabled us to detect a foveolar deficit completely overlooked by the other usual tests. In light of our clinical study, we can assert that the multifocal ERG has yet to be equaled by any other test for analysis of macular function.

Adolescent↗

[Ocular toxicity of deferoxamine: description and analysis of three observations].

INTRODUCTION: Deferoxamine is a specific chelating agent of trivalent anions: iron ion and aluminum ion. The main prescriptions for this treatment are primary non-curable by blood letting hemochromatosis, secondary hemosiderosis, and aluminum intoxication associated with chronic kidney failure. Since the early 1980s, ocular toxicity has been documented in several publications. OBSERVATIONS: We recorded three clinical observations of patients presenting symptoms of an ocular toxicity caused by deferoxamine. The prescription of this treatment related to the presence of secondary hemosiderosis (a case of primitive myelofibrosis and a case of chronic myelomonocytic leukemia treated by blood transfusion) and an aluminum intoxication affecting a patient with chronic kidney failure. All three patients presented a gradual loss of visual acuity. The following were predominantly observed at the fundus examination which showed pigmentary anomalies near the macula such as mottling and dispersion affecting the electrophysiological studies. The termination of the treatment did not result in an improvement in the symptomatology. DISCUSSION: Considering the latest literature on the subject, the indications as well as the pharmaceutical properties of deferoxamine, the ophthalmological symptoms of this intoxication, the additional investigations and the anatomicopathological analyses are restated, together with the current pathogenical hypothesis. CONCLUSION: Deferoxamine can cause ocular toxicity resulting in severe and permanent lesions of the retinal pigment epithelium. The occurrence of disorders of the fundus and visual acuity requires, before and during the treatment, regular ophthalmological monitoring combined with electrophysiological explorations. This allows early treatment of the hematological or kidney disorder.

Aged↗

Isolated late-onset cone-rod dystrophy revealing a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome with the T8993G mitochondrial mutation.

PURPOSE: To report a late-onset cone-rod dystrophy that revealed a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome as a consequence of the T8993G mitochondrial mutation. METHODS: Observational case series. A 42-year-old female disclosed a late-onset retinal dystrophy. The family history revealed that her three sons, one of them deceased at the age of 4, had mental and neurologic impairment of variable severity. The retinal dystrophy of the mother was classified as a cone-rod dystrophy. Retinal dystrophy was subsequently diagnosed in the two surviving sons. Screening for mutation in the mitochondrial DNA (mtDNA) was performed because of the combination of neurologic involvement and retinal dystrophy in this family. RESULTS: Molecular analysis of the mtDNA revealed the ATPase-6 gene T8993G mutation in the mother and the two sons. CONCLUSION: This family illustrates the remarkably variable expression of retinal and systemic manifestations related to the T8993G mutation ranging from an isolated late-onset cone-rod dystrophy to a severe neurodegenerative process with a dramatic outcome. Genetic counseling for retinal dystrophies requires careful evaluation of the familial medical history.

Adenosine Triphosphatases↗

Thermal sensitivity in Tourette syndrome: preliminary report.

The effects of heat on tic symptoms were studied in a sample of 78 adults with Tourette syndrome. 62 men and 16 women completed a survey concerning the type, onset, and course of their tics. 10 adult male subjects also participated in a thermal challenge during which ambient temperature was raised from 22 degrees C to 35 degrees C following a control period. Of the 78, 24% or 19 reported increased tics upon exposure to heat. Compared to the remaining 59 subjects, there were no differences in sex distribution, current age, or overall course of illness. In the thermal challenge, there was general increase in tics that was correlated with sweat rate (r = .55, p = .001). This effect was prominent in 5 of 10 subjects (rs = .29 to .63). There were no mean differences in current age, age of onset, or current severity of symptoms between the five subjects of each group. Tic symptoms in a subgroup of patients with Tourette syndrome may be sensitive to heat. Abnormal heat regulation is not a likely explanation for the observed increase in tics. The increase may be due to normal heat-loss mechanisms through dopaminergic pathways.

Adult↗

Coarctation of the Aorta.

Balloon angioplasty or early surgical correction is recommended once coarctation of the aorta has been diagnosed. Medical management is not a long-term option. The rate of restenosis is higher in infants and children than in adults, but the incidence of residual or late hypertension increases with age at initial intervention. Current angioplasty and stent placement techniques have reduced the rate of aneurysm formation and expanded the types of complex anatomic configurations amenable to nonsurgical intervention. Patients require long-term follow-up for restenosis and late or residual hypertension. Coarctation treatment is straightforward in patients with simple isolated coarctation. In neonates with associated lesions and diffuse arch hypoplasia, aggressive (albeit higher-risk) arch-enlargement procedures can be done at the time of open-heart correction of intracardiac defects. Changes in aortic compliance, vascular reactivity, and vascular homeostasis mechanisms in patients who have late surgery are associated with a higher incidence of residual hypertension.

Journal Article↗

[A new mode of recording retinal activity: multifocal ERG].

Global ERG recordings are only modified in conditions with diffuse or extensive retinal involvement. The use, over the last 6 months, of a new functional testing device: VERIS (visual evoked response imaging system) allows accurate detection and quantification of localized retinal function defects. Our preliminary experience shows that a careful preparation of subjects, standardized testing protocols and a good understanding of the device technology, especially software parameters are mandatory. We report our results on a series of 28 normal volunteers, grouped by age and describe the various graphic presentation of data collected. This technology should allow accurate detection and quantification of retinal functional defects in patients with age related macular degeneration as well as evaluation of visual function in retinitis pigmentosa patients before and after photoreceptor transplantation.

Adult↗

2'-O-methyl-5-formylcytidine (f5Cm), a new modified nucleotide at the 'wobble' of two cytoplasmic tRNAs Leu (NAA) from bovine liver.

The nucleotide analysis of a cytoplasmic tRNA(Leu) isolated from bovine liver revealed the presence of an unknown modified nucleotide N. The corresponding N nucleoside was isolated by different enzymatic and chromatographic protocols from a partially purified preparation of this tRNA(Leu). Its chemical characterization was determined from its chromatographic properties, UV-absorption spectroscopy and mass spectrometric measurements, as well as from those of the borohydride reduced N nucleoside and its etheno-trimethylsilyl derivative. The structure of N was established as 2'-O-methyl-5-formylcytidine (f5CM), and its reduced derivative as 2'-O-methyl-5-hydroxy-methylcytidine (om5Cm). By sequencing the bovine liver tRNA(Leu), the structure of the anticodon was determined as f5CmAA. In addition, the nucleotide sequence showed two primary structures differing only by the nucleotide 47c which is either uridine or adenosine. The two slightly differing bovine liver tRNAs-Leu(f5CmAA) are the only tRNAs so far sequenced which contain f5Cm. The role of such a modified cytidine at the first position of the anticodon is discussed in terms of decoding properties for the UUG and UUA leucine codons. Recently, precise evidence was obtained for the presence of f5Cm at the same position in tRNAs(Leu)(NAA) isolated from rabbit and lamb liver. Therefore, the 2'-O-methyl-5-formyl modification of cytidine at position 34 could be a general feature of cytoplasmic tRNAs(Leu)(NAA) in mammals.

Animals↗

Interleukin 6 upregulates TNF-alpha-dependent C3-stimulating activity through enhancement of TNF-alpha specific binding on rat liver epithelial cells.

The authors investigated the role of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), two major pro-inflammatory cytokines, in the stimulation of the third component of complement (C3) production by rat liver epithelial cells. Though often considered as the most potent inflammatory cytokine, IL-6 alone displayed no activity, whereas TNF-alpha upregulated C3 production in a dose-dependent manner. However, IL-6 was shown to synergistically stimulate C3 production in the presence of TNF-alpha. To account for this interaction, it was postulated that IL-6 modulates the binding of TNF-alpha on liver target cells. That IL-6 increased the binding of TNF-alpha on the surface of the hepatic cells, whereas TNF-alpha alone downregulated its own specific binding capacity is reported. Furthermore, this upregulatory effect of IL-6 was mainly attributable to an increase in the number of plasma membrane TNF-alpha specific receptors, with little change in their affinity. These results suggest that the synergistic IL-6 activity on C3 production may occur, at least partially, through its capacity to upregulate the number of TNF-alpha receptors on the surface of the rat liver epithelial cells.

Animals↗

Baroreceptor modulation of cutaneous vasodilator and sudomotor responses to thermal stress in humans.

1. The influence of baroreceptor unloading on cutaneous vasodilatation was investigated in ten human subjects during dynamic supine cycle ergometer exercise at 28 degrees C. Increases in forearm skin blood flow (venous occlusion plethysmography) and arterial blood pressure (non-invasive) were measured and used to calculate forearm vascular conductance while local chest sweating rate was measured by dew-point hygrometry. Subjects performed two similar exercise protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e. either removed or applied) after 15 min while exercise continued for an additional 20 min. 2. During exercise without LBNP, the body core temperature threshold for vasodilatation (measured as oesophageal temperature, Tc) averaged 37.06 +/- 0.12 degrees C (+/- S.E.M.) and increased to 37.30 +/- 0.09 degrees C (P < 0.05) during exercise with LBNP. The rate of rise of forearm vascular conductance (FVC) per unit increase in Tc (an expression of thermal sensitivity) and peak FVC at 15 min was significantly attenuated during baroreceptor unloading. These effects were rapidly reversed when LBNP was turned off. 3. Baroreceptor unloading during the first 15 min of exercise attenuated the local chest sweating rate, which was also reversed when LBNP was removed. 4. The time course and quickness in which baroreceptor unloading modulated thermoregulatory control of skin blood flow and local chest sweat rate suggests that the interaction between these two homeostatic mechanisms is primarily neurally mediated. The ability of baroreceptor activity to modulate both control of skin blood flow and sweating suggests a common site of interaction, more proximal than the effector organs, and involving the active vasodilator system.

Adult↗

CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis.

Centromere protein-F (CENP-F) is mammalian kinetochore protein that was recently identified by an autoimmune serum (Rattner, J. B., A. Rao, M. J. Fritzler, D. W. Valencia, and T. J. Yen. Cell Motil. Cytoskeleton. 26:214-226). We report here the human cDNA sequence of CENP-F, along with its expression and localization patterns at different stages of the HeLa cell cycle. CENP-F is protein of the nuclear matrix that gradually accumulates during the cell cycle until it reaches peak levels in G2 and M phase cells and is rapidly degraded upon completion of mitosis. CENP-F is first detected at the prekinetochore complex during late G2, and is clearly detectable as paired foci that correspond to all the centromeres by prophase. During mitosis, CENP-F is associated with kinetochores from prometaphase until early anaphase and is then detected at the spindle midzone throughout the remainder of anaphase. By telophase, CENP-F is concentrated within the intracellular bridge at either side of the mid-body. The predicted structure of the 367-kD CENP-F protein consists of two 1,600-amino acid-long coil domains that flank a central flexible core. A putative P-loop nucleotide binding site (ADIPTGKT) is located within the globular carboxy terminus. The structural features deduced from our sequence studies and the spatial and temperal distribution of CENP-F revealed in our cytological and biochemical studies suggest that it may play a role in several mitotic events.

Amino Acid Sequence↗