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Biomedical subjects

T Weiss

Publications and source records attributed to T Weiss.

At least 55 records · Page 3Linked to original sources

Decrease in phantom limb pain associated with prosthesis-induced increased use of an amputation stump in humans.

The experience of phantom limb pain, non-painful phantom limb sensation and telescoping was ascertained by questionnaire in a group of upper extremity amputees wearing a functionally effective Sauerbruch prosthesis which permits extensive use of the affected limb and in a group of patients wearing a cosmetic prosthesis that did little to increase the utilization of the amputation stump. The Sauerbruch prosthesis group exhibited a significant and large decrease in amount of phantom limb pain while the cosmetic prosthesis group showed no change. Neither group experienced a decrease in non-painful phantom limb sensation or telescoping. The amount of phantom limb pain has been found to be highly correlated with the amount of injury-related, afferent-decrease cortical reorganization. It is possible that the increased use of the amputation stump induced by wearing a Sauerbruch prosthesis produced a countervailing use-dependent, afferent-increase type of cortical reorganization that reversed the phantom limb pain. These preliminary results require replication. Their therapeutic implications are discussed.

Adult↗

Determination of urinary 2-thiazolidinethione-4-carboxylic acid after exposure to alkylene bisdithiocarbamates using gas chromatography-mass spectrometry.

This is a newly developed method which permits the quantitative determination of 2-thiazolidinethione-4-carboxylic acid (TTCA, an established biomarker of exposure to CS2) as a metabolite of alkylene bisdithiocarbamates (ABDCs) in human urine. After separation of TTCA from the urinary matrix using liquid-liquid extraction the analyte was converted into its diethyl derivative. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection in single ion monitoring mode. 4-(4-Chloro-2-methylphenoxy)butanoic acid (MCPBA) served as internal standard. The detection limit was 0.7 microg/l in urine. The relative standard deviation of the within-series imprecision was 4.3% at a concentration of 13 microg/l. The relative recovery was within the range of 86 to 98%. In order to determine the suitability of TTCA for biological monitoring after exposure to ABDCs, we analysed 87 24-h urine samples from occupationally exposed workers. The results were compared with the levels of TTCA excreted in urine by 50 control persons without known exposure to dithiocarbamates or CS2. This collective of unexposed persons also provided TTCA reference values for the general population. The urinary TTCA concentrations of the exposed persons were in the range from 0.8 microg/g creatinine to 515 microg/g creatinine. Unexposed persons excreted TTCA in concentrations from below the detection limit to 182 microg/g creatinine. The median concentration found in exposed persons (27 microg/g) was nearly 2.5 times higher than in non-exposed persons (11 microg/g). The difference between the exposed and unexposed collective was highly significant. Assessment of an individual's exposure by determining the level of TTCA in urine nevertheless was not possible. This was due to the relatively wide range of concentrations and because the ranges of both collectives overlapped.

Calibration↗

Power of theta waves in the EEG of human subjects increases during recall of haptic information.

Several studies have reported a functional relationship between spectral power within the theta-band of the EEG (theta-power) and memory load while processing visual or semantic information. We investigated theta power during the processing of different complex haptic stimuli using a delayed recall design. The haptic explorations consisted of palpating the structure of twelve sunken reliefs with closed eyes. Subjects had to reproduce each relief by drawing it 10 s after the end of the exploration. The relationship between mean theta power and mean exploration time was analysed using a regression model. A linear relationship was found between the exploration time and theta power over fronto-central regions (Fp1, Fp2, F3, F7, F8, Fz, C3) directly before the recall of the relief. This result is interpreted in favour of the hypothesis that fronto-central theta power of the EEG correlates with the load of working memory independent of stimulus modality.

Adolescent↗

Shorter turn-around-time and improved patient care in peripheral blood progenitor cell collection procedures.

The collection of peripheral blood progenitor cells (PBPC) requires the combined efforts of the Transfusion Medicine/Hemapheresis and Hematology/Oncology services and HLA/Progenitor Cell and Immunology laboratories. Coordination and communication among these different services and laboratories are key to attaining an optimal collection in a timely manner for the patient undergoing PBPC collection. In an effort to improve patient care by same-day decision to cease or continue collections avoiding unnecessary collections, needless patient trips to the hospital and ultimately increasing patient satisfaction, a flow chart was used to capture the sequence of events. The flow chart served as a powerful tracking tool that defined system process and steps to attain enumeration of CD34+ cells the same day of collection. It provided documentation of work flow from each of the independent operations involved in progenitor cell collection and enumeration turn-around-time including attending and staff time involvement. By using the flow chart, potential and actual problem areas were demonstrated and this allowed for creative thinking and problem solving by individual sections rather than recriminations. Finally, it focused all the staff involved in the common goal of a shorter turn-around-time for CD34+ cell enumeration the same day of collection. This allowed a prompt decision for subsequent leukapheresis as improved service to oncology patients and their physicians.

Adult↗

Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB.

Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications. NF-kappaB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.

Adult↗

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light.

Despite of the approval of Photofrin in various countries, chemically defined sensitizers for photodynamic therapy (PDT) are still needed for the absorption of light in the infrared spectrum, which provides a maximal penetration of light into tissue. Therefore, both the efficacy and the mechanism of action of the clinically approved dye indocyanine green (ICG) and laser irradiation were investigated in vitro. For the investigation of phototoxic effects, HT-29 cells were incubated 24 h prior to irradiation by using different concentrations of ICG (10-500 microM). In each experiment, cells were irradiated using a continuous wave (cw)-diode laser (lambda(ex) = 805 nm, 30 J cm(-2), 40 mW cm(-2)). After laser irradiation, cell viability of dark control and of cells incubated with 500 microM ICG was 1.27+/-0.11 or 0.28+/-0.05 respectively. Using 100 microM ICG and D2O, cell viability was further decreased from 0.46+/-0.03 (H2O) to 0.11+/-0.01 (D2O). Using D2O and 100 microM ICG, the concentration of malondialdehyde, a marker of lipid peroxidation, increased from 0.89+/-0.10 nmol 10(-6) cells to 11.14+/-0.11 nmol 10(-6) cells. Using 100 microM ICG and laser irradiation sodium azide or histidine (50 mM), quenchers of singlet oxygen reduced the cell killing significantly. In contrast, when using mannitol, a quencher of superoxide anion and hydroxyl radical, cell killing was not inhibited. According to the present results, photoactivated ICG seems to kill colonic cancer cells due to the generation of singlet oxygen and the subsequent formation of lipid peroxides. Therefore, ICG might present a promising photosensitizer for PDT; first clinical results confirm these findings.

Cell Death↗

Allatostatin modulates skeletal muscle performance in crustaceans through pre- and postsynaptic effects.

Allatostatins, originally identified in insects as peptide inhibitors of juvenile hormone biosynthesis, are regarded as potent inhibitory regulators of intestinal muscles in insects and crustaceans. However, accumulating data indicate that allatostatins might also be involved in modulation of skeletal neuromuscular events. We show that most ganglia of two isopod crustaceans (Idotea baltica and I. emarginata) contain pairs of large, allatostatin-immunoreactive motor neurons which supply several segmental muscles. Among them are the dorsal extensor muscles, of which some fibres receive immunoreactive, varicose innervation. We demonstrate, on identified muscle fibres, that allatostatin exerts a twofold inhibitory effect: it reduces contractions of single voltage-clamped fibres, and it decreases the amplitude of evoked excitatory junctional currents recorded from individual release boutons. No change in excitation-contraction threshold or in passive membrane parameters was observed. As the amplitude of miniature currents generated by spontaneously released single transmitter quanta was not changed, the inhibitory effect of the peptide on junctional currents must be of presynaptic origin. Supportive results were obtained on leg muscles of the crab Eriphia spinifrons, where allatostatin decreased evoked synaptic currents by reducing the mean number of transmitter quanta released by presynaptic depolarization without affecting the amplitudes of currents generated by single quanta. This effect of allatostatin was similar for two functionally different neurons, the slow and the fast closer excitor. The data show that allatostatin occurs in identified motor neurons of Idotea and exerts complementary pre- and postsynaptic modulatory effects which reduce muscle responses. Thus, allatostatin counteracts the effects of another neuropeptide, proctolin, which is also present in Idotea and causes potentiating effects on the same muscle fibres.

Animals↗

Capillary blood sampling: relation between lancet diameter, lancing pain and blood volume.

The relation between pain of capillary blood sampling and lancet diameter was studied in 52 healthy subjects. The tips of six fingers were pricked with a Softclix(R) II lancing device using lancets with identical facet geometry but needle diameters of 0.3, 0.4 and 0.8 mm. Two penetration depths (0.9 and 1.2 mm) were applied. Pain intensity and blood volume were recorded.At a puncture depth of 0.9 mm, pain did not differ between the three lancets. Pain increased with penetration depth, and at 1.2 mm the thicker lancets were somewhat more painful than the thinner ones. Blood volumes increased with lancet diameter and penetration depth. If the pain for punctures providing just enough blood for a glucose test (>/=10 µl) was compared, there was no difference between the lancets.It can be concluded that lancet diameter is of minor importance for the patient. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome. Clinical implications.

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.

Anthropometry↗

TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR-associated factor 2 and is specific for TNFR60.

Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show that this enhancement is TNFR60 selective, as neither TNF-related apoptosis-inducing ligand/Apo2 ligand-, Apo1/Fas-, ceramide-, nor daunorubicin-mediated cell death was affected by costimulation of TNFR80. We further demonstrate that TNFR-associated factor 2 (TRAF2) is critically involved in both negative and positive regulation of TNF-induced cell death. Overexpression of TRAF2 and of a TRAF2 mutant, deficient in nuclear factor-kappaB activation, selectively desensitized and enhanced, respectively, TNFR60-induced cell death in HeLa cells. However, upon costimulation of TNFR80, which mediates activation of nuclear factor-kappaB and the c-Jun amino-terminal kinase via TRAF2, TNF-induced cell death is drastically enhanced in parental and TRAF2-transfected, but not in TRAF2 (87-501)-transfected cells. These data point to a critical role of TRAF2 in the apoptotic TNFR cross talk, whereby the TNFR80-dependent enhancement of TNFR60-induced cell death is due to TNFR80-mediated negative regulation of TRAF2 function(s). An interference with TRAF2 function was confirmed independently by analysis of c-Jun amino-terminal kinase activation via TNFR60 upon prestimulation of TNFR80. We propose that the apoptotic TNFR cross talk is based on TNFR80-mediated abrogation of antiapoptotic TRAF2-dependent signaling pathways initiated by TNFR60, but not Apo1/Fas or the apoptotic TNF-related apoptosis-inducing ligand receptors.

Adjuvants, Immunologic↗

Determination of the minor whey protein bovine lactoferrin in cheese whey concentrates with capillary electrophoresis.

In our present work we present the determination of bovine lactoferrin in whey concentrates as they are typically produced by milk and cheese industry after production of cheese. Due to the high total protein content the analysis of whey concentrate samples is difficult and even not possible by using capillary zone electrophoresis with UV detection. To enhance the detection sensitivity we applied a more promising approach by using affinity interactions in combination with laser-induced fluorescence detection. By mixing fluoresceine isothiocyanate (FITC)-conjugated polyanionic lipopolysaccharide with the mostly positively charged lactoferrin we found a significant migration time shift which is clearly dependent on the concentration of the added protein. In the second approach we developed an immunoassay using FITC-conjugated specific antibody against bovine lactoferrin. The results of the immunoassay measurements were compared with data obtained by standard enzyme-linked immunosorbent assay analysis.

Animals↗

Reorganization of the somatosensory cortex after amputation of the index finger.

Cortical reorganization occurs within the primary somatosensory and the primary motor cortex after amputation of the arm or forearm. Here we report on a patient showing cortical reorganization after amputation of his right index finger. Our findings indicate that the neural networks within the area of the amputated finger in the somatosensory cortex (SI) were invaded by neighbouring structures, i.e. of neural cell assemblies that subserve the thumb and middle finger of his right hand.

Amputation, Traumatic↗

Dominant-negative FADD inhibits TNFR60-, Fas/Apo1- and TRAIL-R/Apo2-mediated cell death but not gene induction.

Fas/Apo1 and other cytotoxic receptors of the tumor necrosis factor receptor (TNFR) family contain a cytoplasmic death domain (DD) [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] that activates the apoptotic process by interacting with the DD-containing adaptor proteins TNFR-associated DD protein (TRADD) [12] [13] and Fas-associated DD protein (FADD/MORT1) [14] [15], leading to the activation of cysteine proteases of the caspase family [16]. Stimulation of Fas/Apo1 leads to the formation of a receptor-bound death-inducing signaling complex (DISC), consisting of FADD and two different forms of caspase-8 [17] [18] [19]. Transient expression of a dominant-negative mutant of FADD impairs TNFR60-mediated and Fas/Apo1-mediated apoptosis [13] [20], but has no effect on TNF-related apoptosis-inducing ligand (TRAIL/Apo2L)-induced cell death [7] [8] [9] [10] [21]. To study the function of FADD in DD-receptor signaling in more detail, we established HeLa cells that stably expressed a green fluorescent protein (GFP)-tagged dominant-negative mutant of FADD, GFP-DeltaFADD. Interestingly, expression of this mutant inhibited cell death induced by TNFR60, Fas/Apo1 and TRAIL-R/Apo2. In addition, GFP-DeltaFADD did not interfere with TNF-mediated gene induction or with activation of NF-kappaB or Jun N-terminal kinase (JNK), demonstrating that FADD is part of the TNFR60-initiated apoptotic pathway but does not play a role in TNFR60-mediated gene induction. Fas/Apo1-mediated activation of JNK was unaffected by the expression of GFP-DeltaFADD, suggesting that in Fas/Apo1 signaling the apoptotic pathway and the activation of JNK diverge at a level proximal to the receptor, upstream of or parallel to FADD.

Adaptor Proteins, Signal Transducing↗

Brain electrical correlates of pain processing.

Pain is the result of complex neuronal activities within the brain and not simply the result of peripheral activities of the nociceptive system. Pain results from an interaction of many neuronal modules located in different brain areas. This interaction is modified by anticipation, learning, and perception. Electrophysiological phenomena allow the characterization of the information processing associated with pain. This characterization is important for theoretical purposes and for the evaluation of different therapeutic strategies. Furthermore, electrophysiological phenomena support the investigation of functional plasticity in the brain as one of the consequences of chronic pain processing. It is expected that new methods of cortical source analysis will contribute considerably to our understanding of different aspects of pain processing and of the management of pain.

Animals↗

[Starling resister and stability of sleep ventilation].

The upper airway can be described as a collapsible segment (the pharynx) interposed between two rigid bony (the cavum) or cartilaginous (the trachea) segments. Due to this structure, the pharynx behaves as a collapsible tube, in which airflow does not depend on the downstream pressure, but is limited to a maximum value which depends only on the upstream pressure and on the pressure surrounding the collapsible segment; this behavior, known as a Starling resistor can be modeled by the waterfall effect. Thus, the upper airways can be in three different conditions: an occluded condition, in which no flow is possible, a patent condition, in which flow depends on the difference between upstream and downstream pressures (according to Poiseuille's law), and a situation in which flow is limited. The behavior of the upper airway is largely dependent on its anatomic structure, but functional factors play a critical role. Among these sleep state is both a determinant of the collapsibility of the pharynx, and determined by the simulation of upper airway mechanoreceptors whose activity depends on the activity of respiratory muscles. Thus the interplay of three factors: ventilatory drive, upper airway collapsibility, and arousal threshold can predict most of the situations of stable and unstable ventilatory behavior during sleep. The level of the arousal threshold governs the stability of the ventilatory pattern, as it determines whether a combination of slow, respiratory effort, and blood gases can be maintained or is interrupted by an arousal.

Airway Resistance↗

Acute effects of haemodialysis on cutaneous microcirculation in patients with peripheral arterial occlusive disease.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an increasing problem in patients on maintenance haemodialysis. Alterations in microvascular perfusion accompany and complicate arteriosclerosis of large vessels and might contribute to the disease process. The aim of the study was to investigate the acute effects of haemodialysis on the cutaneous microcirculation in 26 patients with and without intermittent claudication. METHODS: Cutaneous perfusion was assessed by measuring transcutaneous oxygen pressure (tcPO2) and skin temperature at the dorsum of the foot. After standardized cooling to 15 degrees C of a 2cm2 skin area, the time to reach baseline skin temperature was evaluated as an indirect parameter of reactive hyperaemia. RESULTS: During haemodialysis, tcPO2 dropped significantly in both groups. The decrease in tcPO2 was more pronounced in patients with PAOD (20% vs 15% n.s.). The reactive hyperaemia response was reduced significantly in patients with intermittent claudication indicated by a prolonged time to reach baseline skin temperature after cooling. Values of tcPO2 and reactive hyperaemia did not reach baseline values at the end of haemodialysis in either group. CONCLUSIONS: Nutritive skin perfusion is impaired during haemodialysis. These changes are more pronounced in patients with PAOD and persist after dialysis. These findings are relevant for the treatment of patients with vascular disease on maintenance haemodialysis.

Adult↗

Long-term effects of nerve blocks in chronic pain.

Regional blockade techniques have been of crucial importance for decades in chronic pain therapy, but in recent years some developments have made a new definition of the status of invasive procedures necessary. The realization of chronic pain as a multifactorial process led to the establishment of an interdisciplinary approach to pain therapy, leaving blockades as only one step in a multimodal therapy. The mainstay of local anaesthetic blocks now is diagnostic and prognostic, but correct interpretation of the results is limited by different factors, and controlled studies on the diagnostic value of local anaesthetic blockade are lacking. In cancer pain, invasive procedures are necessary in only a few cases. Some neuroablative techniques can offer long-term pain reduction. In non-cancer pain, neurodestructive procedures should be reserved for some special indications (e.g. lumbar sympathetic neurolytic blocks in ischaemic diseases). In a great number of chronic pain conditions the sympathetic nervous system is involved or even has a central status. In the acute stage of these diseases sympathetic blockades can be the therapy of choice. There is no disease in which different invasive procedures are performed so frequently and so uncritically as in chronic low back pain. Up to now, however, all controlled studies of invasive procedures only demonstrated short-term effects and failed to prove long-term efficacy. Therefore any invasive technique should only be performed in well-selected patients over a defined period and with a limited number of blockades.

Journal Article↗