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Biomedical subjects

S Wolf

Publications and source records attributed to S Wolf.

At least 37 records · Page 2Linked to original sources

[Eye globe reconstruction after severe injury of the posterior segment].

Severe injuries of the posterior eye segment mostly occur during perforation or rupture of the globe. The first treatment includes primary surgical repair of the ocular wound and prophylactic scleral buckling in case of involvement of the posterior segment. Thereafter, a vitrectomy should be performed to remove vitreous hemorrhage and intraocular foreign bodies and to achieve a stable attachment of the retina. Therefore, temporary perfluorocarbon and permanent silicone oil tamponade are used. A predictor of poor visual outcome is the presence of retinal and choroidal injury. In our patients, the most important prognostic factor was the initial visual acuity after the injury. Vitrectomy can significantly reduce the incidence of enucleation. Currently, better visual outcome is achieved by advances in surgical techniques.

Eye Injuries, Penetrating↗

Lipofundin-induced intracranial pressure rise after severe traumatic brain injury--a case report.

Early nutrition is a recognized component of neurosurgical intensive care treatment. The authors present the case of a patient suffering from severe traumatic brain injury who responded with reproducible intracranial pressure (ICP) crisis to infusion of Lipofundin, a fatty soybean oil-based emulsion for parenteral nutrition. During the described ICP rise, the patient remained hemodynamically stable, therefore an anaphylactic reaction seems to be unlikely. An increase of brain tissue oxygenation parallel to the ICP rise in this case is suggestive for increased cerebral blood flow as a cause of ICP elevation after application of Lipofundin. Without multimodal monitoring and data storage, the described side effect of Lipofundin in our patient would have been difficult to identify.

Accidental Falls↗

Conversion of biarticular to monoarticular muscles as a component of multilevel surgery in spastic diplegia.

We treated 20 children (40 limbs) with diplegic cerebral palsy who could walk by multilevel soft tissue operative procedures including conversion of the biarticular semitendinosus and gastrocnemius to monoarticular muscles. The mean age at surgery was 11.5 years (5.6 to 17.0). All patients underwent clinical and radiological examination and three-dimensional instrumented gait analysis before and at a mean of 3.1 years (2.0 to 4.5) after surgery. The passive range of movement at the ankle, knee and hip showed improvement at follow-up. Kinematic parameters indicated a reduced pelvic range of movement and improvement of extension of the knee in single stance after operation (p < 0.0001). However, post-operative back-kneeing was detected in five of the 40 limbs. The kinetic studies showed that the power of the hamstrings and plantar flexors of the ankle was maintained while the maximum knee extensor moment during stance was reduced. The elimination of knee flexor activity of semitendinosus and gastrocnemius combined with transfer of distal rectus femoris led to an improvement in gait as confirmed by gait analysis.

Adolescent↗

A mouse model for cystinuria type I.

Cystinuria, one of the most common inborn errors of metabolism in humans, accounts for 1-2% of all cases of renal lithiasis. It is caused by defects in the heterodimeric transporter system rBAT/b0,+AT, which lead to reduced reabsorption of cystine and dibasic amino acids through the epithelial cells of the renal tubules and the intestine. In an N-ethyl-N-nitrosourea mutagenesis screen for recessive mutations we identified a mutant mouse with elevated concentrations of lysine, arginine and ornithine in urine, displaying the clinical syndrome of urolithiasis and its complications. Positional cloning of the causative mutation identified a missense mutation in the solute carrier family 3 member 1 gene (Slc3a1) leading to an amino acid exchange D140G in the extracellular domain of the rBAT protein. The mouse model mimics the aetiology and clinical manifestations of human cystinuria type I, and is suitable for the study of its pathophysiology as well as the evaluation of therapeutic and metaphylactic approaches.

Amino Acid Sequence↗

Clinical findings in macular hole surgery with indocyanine green-assisted peeling of the internal limiting membrane.

PURPOSE: Indocyanine green (ICG) staining of the internal limiting membrane has facilitated ILM peeling in macular hole surgery. However, it has been reported that ICG-assisted peeling of the ILM may result in retinal damage and unfavorable functional outcome. Therefore, we analyzed our visual and anatomical results of ICG assisted macular hole surgery. METHODS: In a retrospective study the records of a consecutive series of 37 patients with full-thickness idiopathic macular holes operated with ICG-assisted ILM peeling by a single surgeon were analyzed. All patients underwent a standard three-port vitrectomy with surgically induced posterior vitreous detachment, staining of the ILM with ICG, peeling of the ILM in a circular manner around the fovea, and SF6 20% endotamponade. RESULTS: A total of 37 patients (37 eyes) were included in the study. The mean age was 69+/-7 years (range 52-81 years), and there were 26 women and 11 men. The follow-up ranged from 6 to 30 months (mean 18+/-6 months). At baseline visual acuity ranged from 20/400 to 20/40. Anatomically, 13 eyes had stage 2 holes, 21 eyes (57%) stage 3 holes, and three eyes stage 4 holes. At the postoperative visit (8-12 weeks after surgery) anatomical closure of the macular hole was achieved in 36 eyes. Visual acuity ranged between 20/400 and 20/20. At the last follow-up after initial surgery the macular hole was closed in all eyes. Visual acuity ranged from 20/200 to 20/20. CONCLUSION: In our retrospective series anatomical and functional results of macular hole surgery with ICG-assisted peeling of the ILM are satisfactory. Primary hole closure was achieved in 97% of eyes and visual acuity increased in 62% of eyes in our series.

Aged↗

[Growth of sporadic vestibular schwannomas correlates with Ki-67 proliferation index].

BACKGROUND: Sporadic vestibular schwannoma show a wide variability of their growth rate. Some tumors might remain quiescent for a long time without symptoms and other tumors might suddenly enlarge. Sometimes during surgical removal of tumors, it is useful to have a parameter for the prediction of the further growth potential of the schwannoma, especially if tumor resection results in functional impairment of the facial nerve. An often used histological parameter for growth rate of tumor cells is the proliferation index. METHODS AND PATIENTS: In our study we observed a series of 50 patients with neurinoma of the vestibular nerve by "wait and scan". After the first magnetic resonance imaging (MRI) all patients were controlled by a second MRI. The time between the MRIs ranged between 3 and 26 months (median 9). In 45 of 50 patients a surgical removal of the tumor by transtemporal approach followed. RESULTS: The proliferation index (Ki-67) was identified in the histological tumor specimens. The next step was the correlation of proliferation index and "tumor doubling time" (TDT). The volume of the tumors was provided by measuring three diameters of the tumors in MRI and calculating the volume with a formula. The volume of the tumors were used to calculate tumor growth and TDT. 10 patients showed no tumor growth during follow up. The average TDT in 40 cases was 22 months (SD 16). In 33 cases we were able to determine a proliferation index, which showed an average score of 1.99 %. Statistical analysis showed a correlation between proliferation index and TDT with a coefficient of - 0.42 (s: 0.014). In two cases with relevant clinical tumor growth (TDT: 12 months), the MIB-1 index was nearly 0 % in different areas of the tumor specimen. May be in these cases, the cell proliferation declined just before operation. On the other hand we found one patient with a high proliferation index of 3.3 % and a rather long TDT of 19 months. CONCLUSIONS: The determination of proliferation can serve as a further decision guidance during surgery of vestibular schwannoma.

Cell Division↗

Surgery and outcome for aneurysmal subarachnoid hemorrhage in elderly patients.

OBJECTIVE: The goal was to report treatment results of elderly patients (over 70 years) who underwent clipping of aneurysms after subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: From 1994 to 2000 41/284 (14%) patients older than 70 years were operated on aneurysmal SAH in our department. Localization of ruptured aneurysm was anterior communicating artery (n = 14), middle cerebral artery (n = 14), internal carotid artery (n = 6), anterior cerebral artery (n = 2), pericallosal artery (n = 1) and multiple in 4 patients. We used the Hunt and Hess classification for initial grading and the Glasgow Outcome Score at day 30 after surgery. RESULTS: Patients with HH 1-3 had a low mortality (1/18, 6%), whereas 9 of 23 patients (39%) with HH 4-5 decreased within 30 days after surgery. Overall mortality was 24.5% (10/41) at 30 days after surgery. Most patients (n = 32) underwent early surgery (within 72 hours). Shunt dependent hydrocephalus developed in 15 patients (37%). The outcome was better in patients graded HH 1-3, in those without serious atherosclerotic changes in angiography, and in AcoA and ICA localization compared to MCA. CONCLUSION: Advanced age does not preclude successful surgery for ruptured aneurysm. Most important factor for outcome was a good initial clinical status, though the majority of our patients presented with poor grades. Early surgical clipping and postoperative intensive care can attain a favorable outcome in a significant percentage of elderly patients.

Age Factors↗

The safety of the open lung approach in neurosurgical patients.

A recent randomized controlled trial in patients with ARDS showed the beneficial effect of mechanical ventilation according to the so called Open Lung Approach, consisting of low tidal volumes and elevated PEEP settings after performing recruiting maneuvers. However, neurosurgical patients were excluded from this and other ARDS trials due to concerns of intracranial deterioration. In this report, we present the clinical data of eleven patients with known intracranial pathology and concomitant ARDS which was treated according to the Open Lung concept. The mean oxygenation index (paO2/FiO2) increased from 132 +/- 88 to 325 +/- 64 measured 24 hours after initiation of Open Lung ventilation (p < 0.001). Mean PEEP level after the first recruiting maneuver was 14.9 +/- 3.2 mmHg. Comparison of mean and peak ICP values over 24 hours of time before and after the first recruitment maneuver revealed a non-significant decline in ICP despite a moderate increase in mean paCO2. Although two patients needed additional ICP treatment, no patient had to be withdrawn from Open Lung ventilation. In our series, Open Lung ventilation in neurosurgical patients with ARDS was a safe method to improve oxygenation. Careful ICP monitoring provided, there is no reason to withhold this modern ARDS treatment in the neurosurgical intensive care unit.

Brain Injuries↗

[Immunonutritive enteral feeding in the critically ill].

Since imbalances in the immune system of the critically ill patient have been demonstrated, the role of the gastrointestinal tract for the pathogenesis of multiple organ failure has been a focus of research in intensive care medicine. Particularly, the integrity of the intestinal barrier function has been studied experimentally and clinically. The enormous number of gram-negative bacteria up to 10(11)/ml intestinal liquid inducing the release of significant amounts of endotoxin, is considered to be a vital threat to the intensive care unit (ICU) patient. Acute failure of the intestinal barrier following various types of severe shock or following parenteral nutrition inducing atrophy of intestinal mucosa may lead to multiple organ dysfunction. Maintenance of hemodynamic stability is a mainstay of therapy of the critically ill. In addition, the intestinal integrity can be preserved by the early onset of enteral nutrition. Moreover, recent concepts of enteral nutrition using immunomodulating nutrients like omega-3-fatty acids, glutamine, arginine, and nucleotides are under clinical evaluation.

Critical Illness↗

M-cone opsin gene number does not correlate with variation in L/M-cone sensitivity.

Molecular genetic studies demonstrate that the human cone opsin gene array on the q-arm of the X-chromosome typically consists of one long-wave-sensitive (L) cone opsin gene and from one to several middle-wave-sensitive (M) cone opsin genes. Although the presence of the single L-cone opsin gene and at least one M-cone opsin gene is essential for normal red-green colour discrimination, the function of the additional M-cone opsin genes is still unclear. To investigate whether any variations in phenotype correlate with differences in the number of M-cone opsin genes, we selected 13 normal trichromat males, for whom four independent molecular techniques have exactly determined their number of M-cone opsin genes, ranging from one to four. Their phenotype was characterized by estimating their foveal L- to M-cone ratio from heterochromatic flicker photometric (HFP) thresholds, by measuring the wavelength corresponding to their 'unique yellow', and by determining their L- and M-cone modulation thresholds (CMTs). No correlation was found between these psychophysical measures and the number of M-cone opsin genes. Although, we found a reasonably good correlation between the L/M-cone ratios based on HFP and on CMT, we did not find any correlation between the estimated L/M-cone ratios and the settings of 'unique yellow'. Our results accord with previous molecular genetic studies that suggest that only the first two genes in the X-linked opsin gene array are expressed.

Color Perception↗

Do angiographic data support a detailed classification of hypertensive fundus changes?

The eye is a target organ as well as an established prognostic indicator of arterial hypertension. Based on the ophthalmoscopically visible alterations, several classifications, the majority of them grading hypertensive fundus changes into four stages, have been suggested. Moreover, assessment of hypertensive alterations of the perivoveal microcirculation has become possible by means of fluorescein angiography. However, it has not yet been evaluated whether an angiographic equivalent for the ophthalmoscopic classifications exists. We therefore compared the perifoveal microcirculation of hypertensive patients who were staged according to the classification of Neubauer, a modification of the classification of Keith and Wagener, among each other and with that of normal subjects. According to Neubauer, who distinguishes between fundus hypertonicus (stages I-II) and hypertensive retinopathy (stages III-IV), we divided the patients (n = 143) into four groups: stage I (n = 49), stage II (n = 72), stage III (n = 16), and stage IV (n = 6). All patients underwent fluorescein angiography performed with a scanning laser ophthalmoscope. By means of digital image analysis we quantified the following parameters: (1) perifoveal intercapillary area (PIA), (2) the area of the foveal avascular zone (FAZ), and (3) capillary blood velocity (CBV). All patients with arterial hypertension demonstrated a rarefaction of the perifoveal capillary bed and a decrease of capillary blood velocity as compared with normal subjects. Significant changes of PIA (P < 0.05) and CBV (P < 0.05) were seen between mild (I-II) and severe stages (III-IV) of hypertensive retinopathy, but neither between stages I and II nor between stages III and IV. Our findings indicate significant angiographic differences between mild and severe form of hypertensive retinopathy, however, unlike in ophthalmoscopy, a differentiated division into four stages is not possible.

Adult↗

[A modular method for automated evaluation of gait analysis data].

A modular methodology for automated gait data evaluation: The aim of Instrumented Gait Analysis is to measure data such as joint kinematics or kinetics during gait in a quantitative way. The data evaluation for clinical purposes is often performed by experienced physicians (diagnosis of specific motion dysfunction, planning and validation of therapy). Due to subjective evaluation and complexity of the pathologies, there exists no objective, standardized data analysis method for these tasks. This article covers the development of a modular, computer-based methodology to quantify the degree of pathological gait in comparison to normal behavior, as well as to automatically search for interpretable gait abnormalities and to visualize the results. The outcomes are demonstrated with two different patient groups.

Biomechanical Phenomena↗

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury.

OBJECTIVE: To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomised, controlled study. METHODS: Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). CONCLUSION: In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.

Analysis of Variance↗

Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues.

At least five distinct carrier proteins form the family of mammalian cationic amino acid transporters (CATs). We have cloned a cDNA containing the complete coding region of human CAT-3. hCAT-3 is glycosylated and localized to the plasma membrane. Transport studies in Xenopus laevis oocytes revealed that hCAT-3 is selective for cationic L-amino acids and exhibits a maximal transport activity similar to other CAT proteins. The apparent substrate affinity and sensitivity to trans-stimulation of hCAT-3 resembles most closely hCAT-2B. This is in contrast to rat and murine CAT-3 proteins that have been reported to display a very low activity and to be inhibited by neutral and anionic L-amino acids as well as D-arginine (Hosokawa, H., et al. (1997) J. Biol. Chem. 272, 8717-8722; Ito, K., and Groudine, M. (1997) J. Biol. Chem. 272, 26780-26786). Also, in adult rat and mouse, CAT-3 has been found exclusively in central neurons. Human CAT-3 expression is not restricted to the brain, in fact, by far the highest expression was found in thymus. Also in other peripheral tissues, hCAT-3 expression was equal to or higher than in most brain regions, suggesting that hCAT-3 is not a neuron-specific transporter.

Amino Acid Sequence↗

B-cell neoplasia associated gene with multiple splicing (BCMS): the candidate B-CLL gene on 13q14 comprises more than 560 kb covering all critical regions.

Deletions in chromosomal band 13q14.3 occur in >50% of B-cell chronic lymphocytic leukemias (B-CLL) and mantle cell lymphoma, indicating the localization of a tumor suppressor gene involved in the pathomechanism of these diseases. Within a 400 kb recurrently deleted segment at least two minimally deleted subregions had been reported. For the two genes residing in the proximal subregion, initially named LEU1 and LEU2, a pathogenic role has not yet been established. We report here that LEU1 is only a small portion of a large gene, which spans all previously reported critical subregions including the distal subregion. This gene, designated B-cell neoplasia-associated gene with multiple splicing (BCMS), is composed of at least 50 exons spanning >or=560 kb of genomic DNA and is expressed in more than 20 RNA splicing variants. While tissue-specific expression of RNA variants was observed, there was no evidence for the expression of a variant specific for B-CLL. Sequence analysis of the RNA variants suggests that BCMS transcripts belong to the group of non-coding RNAs. The alignment of the gene with all critical subregions provides a strong argument for BCMS being the most likely candidate for the tumor suppressor gene in 13q14 involved in the leukemogenesis of B-CLL. Due to the limited understanding of functional RNAs, however, it remains difficult to prove the pathogenic role of BCMS.

Alternative Splicing↗

A light, nontoxic interleukin 12 protocol inhibits HER-2/neu mammary carcinogenesis in BALB/c transgenic mice with established hyperplasia.

With a slight asynchronous but consistent progression, all of the mammary glands of female BALB/c mice transgenic for the transforming rat HER-2/neu oncogene progress to atypical hyperplasia and to invasive carcinoma. Previous studies have shown that chronic administration of interleukin (IL) 12 started at the 2nd week of age hampers this progression because of its ability to inhibit tumor angiogenesis and activate a nonspecific immune response. Here we show that a similar inhibition is achieved when 7-week-old mice with fully blown atypical hyperplasia receive a weekly injection of 100 ng IL-12 for 16 times. This lower-dose and later IL-12 administration induces high and sustained levels of serum IFN-gamma equivalent to those elicited by more frequent administrations. A lower-dose and less toxic treatment may thus be envisaged as a possible option in the management of preneoplastic mammary lesions.

Animals↗