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Biomedical subjects

T Frieling

Publications and source records attributed to T Frieling.

At least 37 records · Page 2Linked to original sources
PubMed1999

Extraesophageal autonomic dysfunction in patients with achalasia.

A disagreement exists as to whether extraintestinal parasympathetic autonomic function is altered in patients with esophageal achalasia. Therefore, we assessed autonomic dysfunction in esophageal achalasia and considered the most relevant parameters of parasympathetic autonomic function in these patients. In a prospective study, heart rate variation and pupillary function were investigated in 15 patients with achalasia of the esophagus and in 15 controls by application of a battery of standardized autonomic function tests. Significant differences between patients and controls were detected for various parameters of heart rate variation and pupillometry. When compared to values obtained from large groups of healthy subjects, none of the controls but 11 patients had at least one abnormal parameter of parasympathetic autonomic function. It is suggested that in esophageal achalasia parasympathetic dysfunction that extends beyond the gastrointestinal tract can be frequently detected. This finding supports the view of a generalized alteration of the autonomic nervous system in achalasia.

Adult↗
PubMed1999

Cortical activation during oesophageal stimulation: a neuromagnetic study.

We investigated the neuromagnetic responses to mechanical stimulation of the oesophagus. In six healthy right-handed volunteers (mean age 31.6 years) the proximal and distal oesophagus were stimulated by electronically controlled pump-inflation of a silicone balloon once every 4.5-5.5 sec (dwell time 145 msec). The balloon volume was adjusted to induce different sensation levels (i) just above threshold of perception, (ii) strong sensation and (iii) painful sensation. Evoked magnetic brain responses were recorded time-locked to stimulus onset with a Neuromag-122TM whole-head neuromagnetometer and modelled as equivalent current diploe (ECD) sources. ECDs were superimposed on individual magnetic resonance imaging (MRI) scans. Magnetic brain responses following distal oesophageal stimulation were adequately explained by a time-varying 2-4 dipole model with unilateral or bilateral sources in second somatosensory cortex and later sources in the frontal cortex. With increasing stimulus intensities, latencies of the sources decreased and amplitudes increased. Proximal oesophageal stimulation led to activation of source areas spatially similar to those of distal oesophageal stimulation but with shorter response latencies. Both painful and nonpainful mechanical stimulation of the oesophagus activate the second somatosensory cortex (SII). Evidence for topographic organization of oesophageal afferents in SII is poor.

Adult↗
PubMed1999

Different cortical organization of visceral and somatic sensation in humans.

Sensory stimuli from the visceral domain exhibit perceptual characteristics different from stimuli applied to the body surface. Compared with somatosensation there is not much known about the cortical projection and functional organization of visceral sensation in humans. In this study, we determined the cortical areas activated by non-painful electrical stimulation of visceral afferents in the distal oesophagus, and somatosensory afferents in the median nerve and the lip in seven healthy volunteers using whole-head magnetoencephalography. Stimulation of somatosensory afferents elicited short-latency responses (approximately 20-60 ms) in the primary somatosensory cortex (SI) contralateral (median nerve) or bilateral (lip) to the stimulated side, and long-latency responses (approximately 60-160 ms) bilaterally in the second somatosensory cortex (SII). In contrast, stimulation of visceral oesophageal afferents did not evoke discernible responses in SI but well reproducible bilateral SII responses (approximately 70-190 ms) in close vicinity to long-latency SII responses following median nerve and lip stimuli. Psychophysically, temporal discrimination of successive stimuli became worse with increasing stimulus repetition rates (0.25 Hz, 0.5 Hz, 1 Hz, 2 Hz) only for visceral oesophageal, but not for somatosensory median nerve stimuli. Correspondingly, amplitudes of the first cortical response to oesophageal stimulation emerging in the SII cortex declined with increasing stimulus repetition rates whereas the earliest cortical response elicited by median nerve stimuli (20 ms SI response) remained unaffected by the stimulus frequency. Our results indicate that visceral afferents from the oesophagus primarily project to the SII cortex and, unlike somatosensory afferents, lack a significant SI representation. We propose that this cortical projection pattern forms the neurophysiological basis of the low temporal and spatial resolution of conscious visceral sensation.

Adult↗
PubMed1999

Cardiotoxicity of the antiproliferative compound fluorouracil.

The antimetabolite fluorouracil (5-FU) is frequently administered for chemotherapy of various malignant neoplasms. The drug is well known for its adverse effects involving bone marrow, skin, mucous membranes, intestinal tract and central nervous system, whereas its cardiotoxicity is less familiar to clinicians. The pathophysiology of fluorouracil-associated cardiac adverse events is controversial and conclusions are based on clinical studies and case reports more than on solid experimental evidence. While clinical and electrocardiographic features suggest myocardial ischaemia as a main aetiological factor, possibly induced by coronary vasospasm, histomorphological and biochemical studies indicate a more direct drug-mediated cytotoxic action. Estimates of the overall incidence of fluorouracil cardiotoxicity have varied widely from 1.2 to 18% of patients. Patients may present with angina-like chest pain, cardiac arrhythmias or myocardial infarction. There is no unequivocally effective prophylaxis or treatment in this syndrome. Once fluorouracil administration is discontinued symptoms are usually reversible, although fatal events have been described. The overall mortality rate has been estimated to be between 2.2 and 13.3%. There is a high risk of relapse when patients are re-exposed to this drug following previous cardiac incidents. From the present data it is concluded that cardiotoxicity is a relevant but underestimated problem in fluorouracil treatment. Since the mechanisms of fluorouracil-associated cardiotoxicity are not yet fully understood, all patients undergoing this chemotherapy have to be carefully evaluated and monitored for cardiac risk factors and complaints. After cardiotoxic events, fluorouracil should definitely be withdrawn and replaced by an alternative antiproliferative regimen.

Antimetabolites, Antineoplastic↗
PubMed1999

Fecal excretion of alpha 2-macroglobulin: a novel marker for disease activity in patients with inflammatory bowel disease.

BACKGROUND: Quantification of fecal alpha 1-antitrypsin (AAT) excretion is established for estimation of enteric protein loss and assessment of disease activity in inflammatory bowel disease (IBD). In contrast, little is known about prevalence, course, and clinical significance of intestinal leakage of larger-size serum antiproteinases in these disorders. SUBJECTS AND METHODS: Firstly, 23 IBD patients (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 6) were examined at 34 independent episodes (relapse, n = 16, remission, n = 18) for parallel serum and fecal alpha 2-macroglobulin (AMG) and AAT concentrations by standard immunonephelometry, and compared to 40 healthy controls. From these IBD patients, secondly, a random cohort of twelve individuals (9 CD, 3 UC) was prospectively followed for those parameters at about monthly intervals for 7-14 (median 10.5) months. RESULTS: The threshold of detection for fecal AMG concentration was about 0.06 mg per gram dry weight stool (mg/g dws) under the present analytical conditions. While in healthy subjects fecal AMG was demonstrated at very low levels only (< or = 0.07 mg/g dws), it was found in CD and UC patients at elevated concentrations of < 0.06-3.18 (median 0.17) and < 0.06-1.91 (median 0.40) mg/g dws, respectively. Fecal AMG contents were more increased in active IBD compared to quiescent disease (p = 0.03), and they correlated to Crohn's Disease Activity Index in CD patients (p = 0.05), while not to Clinical Activity Index in UC individuals (p = 0.46). Post hoc evaluation of follow-up data suggested two distinct groups of IBD patients either with or without consistently detectable fecal AMG excretion, with the first ones exhibiting a more active clinical course than the latter ones (p < or = 0.02). CONCLUSIONS: AMG is excreted in feces of healthy subjects in traces only, while its stool concentration is largely increased in IBD patients where it reflects clinical disease activity. This novel stool parameter may be of potential value in the diagnostic and prognostic management of these individuals.

Adolescent↗
PubMed1998

[How accurate is preoperative staging as a basis for treatment decisions in gastric carcinoma?].

The treatment of advanced gastric carcinoma by various neoadjuvant and adjuvant multimodal therapy regimes is under current investigation to improve the poor outcome of these patients. Therefore, pretherapeutic tumor staging according to the TNM classification is essential for the optimal application of various therapeutic modalities. According to recent studies, endoscopic ultrasonography (EUS) is the most sensitive technique in measuring tumor infiltration (T-staging). In addition, although less reliable compared to the T-staging, the sensitivity of EUS in assessing lymph node status (N-staging) is superior to computed tomography and conventional ultrasound. Pretherapeutic laparoscopic investigation may give additional important information about tumor stage. This overview describes the significance of various diagnostic techniques that can be applied in tumor staging investigations.

Adenocarcinoma↗
PubMed1998

Quantification of fecal alpha 1-antitrypsin excretion for assessment of inflammatory bowel diseases.

Determination of fecal excretion of the serum proteinase inhibitor alpha(1)-antitrypsin (AAT) is established for quantification of intestinal protein loss. It was demonstrated to be increased both in quiescent and in active inflammatory bowel diseases (IBD, Crohn's disease and ulcerative colitis). The (patho)physiological rationale for measuring fecal AAT excretion and its role in the diagnostic and prognostic assessment of these disorders will be critically reviewed. Experimental and clinical data were selected from computerized MEDLINE literature search, manual review of bibliographies, and personal experiences of the authors. In IBD patients, fecal AAT excretion corresponds to gross assessment of clinical disease activity, endoscopic degree of intestinal inflammation, and any response to treatment. It appears to be an early indicator of subclinical bowel disease and its imminent exacerbation. However, there is neither strict correlation to summarizing clinical disease activity indices, nor to extent or location of intestinal inflammation. Fecal AAT excretion was also found to be elevated in active pouchitis, and to correlate to its severity. In summary, estimation of fecal AAT excretion is a sensitive, but non-specific parameter reflecting enteric inflammation in IBD individuals. It proved to be an independent supplementary variable for monitoring their intestinal disease activity, with some predictive value for their forthcoming clinical course.

Feces↗
PubMed1998

Polarized enteric submucosal circuits involved in secretory responses of the guinea-pig proximal colon.

1. Neuronal retrograde tracing with the dye DiI (1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), in combination with immunohistochemical detection of choline acetyltransferase (ChAT) and vasoactive intestinal peptide (VIP), were used to identify the innervation of the mucosa of the guinea-pig proximal colon by submucosal neurones. Ussing chamber experiments were performed to measure changes in short circuit current (delta Isc) evoked by electrical stimulation of the oral or anal end of the preparation. 2. The tracing studies revealed that the mucosa was primarily innervated by descending neurones (78%); the vast majority of these were VIP positive (85%). The numerically smaller ascending pathway (13%) was predominantly ChAT positive (69%). A small population (9%) of DiI-labelled neurones projected circumferentially. 3. Ussing chamber experiments revealed that oral electrical stimulation induced a significantly larger delta Isc than anal stimulation. The VIP antagonist VIP(6-28) significantly reduced only orally induced delta Isc. Anally induced delta Isc were significantly more atropine sensitive that orally induced delta Isc. Tissue incubation with carbachol or VIP significantly potentiated delta Isc induced by VIP and carbachol, respectively, indicating cross-potentiation. 4. This study provides the first functional demonstration of polarized innervation patterns from submucosal neurones to enteric mucosa. The ascending ChAT and descending VIP pathways suggest the existence of reflexes resulting in preferential release of VIP or acetylcholine. The distinct pathways might favour the observed cross-potentiation of cholinergic and VIPergic mediated secretion.

Action Potentials↗
PubMed1998

Somatic and limbic cortex activation in esophageal distention: a functional magnetic resonance imaging study.

Little is known about the cerebral representations of visceral sensations in humans. Using functional magnetic resonance imaging (fMRI), we mapped the cortical areas of the human brain that were activated by mechanical stimulation of the esophagus in 5 healthy volunteers. Stimulation probes were placed into the distal part of the esophagus and inflated to produce a local distention. The cerebral activation pattern was related to the strength and quality of the stimulus. The weakest stimulus accompanied by a well-localized albeit weak retrosternal sensation activated only the parietal opercular cortices, probably including the secondary somatosensory cortex (SII). Additional activation of the primary sensorimotor cortex (SI) at the level of the face and mouth representation as well as of the right premotor cortex was found during repetitive distention of the esophagus at 0.5 Hz. Repetitive stimulation at 1 Hz additionally activated the insula bilaterally. The strongest distention stimulus, which caused a painful retrosternal sensation, resulted in an activation of the anterior cingulate cortex. Our findings demonstrate that SII is the primary cortical target of visceral afferents originating in the esophagus. Limbic structures become engaged when the visceral sensation is unpleasant or painful.

Adult↗
PubMed1998

Treatment of radiation proctitis with hyperbaric oxygen: what is the optimal number of HBO treatments?

AIM: Our objective was to investigate the effectiveness of hyperbaric oxygenation (HBO) in the treatment of radiation proctitis. The current literature was reviewed with regard to the necessary number of HBO treatments. PATIENTS AND METHODS: Two patients with proctitis after pelvic irradiation were treated with 40 and 38 HBO treatments, respectively. Hyperbaric oxygenation was delivered at 240 kPa over 90 min. RESULTS: In one patient, proctosigmoidoscopy showed a significant improvement after 40 HBO sessions. The other patient interrupted therapy after 38 HBO treatments without subjective change. The reported number of HBO sessions for a successful treatment of radiation proctitis ranges from 12 to 90. CONCLUSION: HBO should be considered before more invasive treatment modalities are performed for radiation proctitis.

Aged↗
PubMed1998

Post- and presynaptic effects of norepinephrine in guinea-pig colonic submucous plexus.

Intracellular recording techniques were used to investigate the effects of norepinephrine on submucous neurones in the guinea-pig distal colon. In 81% of the neurones, pressure microejection of norepinephrine produced a membrane hyperpolarization associated with a decrease in excitability and input resistance. Microejection of clonidine (1 microM) mimicked the norepinephrine-induced hyperpolarization, whereas both phentolamine (1 microM) and yohimbine (1 microM) reversibly suppressed it. Superfusion of norepinephrine (1 nM - 10 microM) hyperpolarized the cells in a concentration-dependent manner. Norepinephrine and clonidine (1 nM - 10 microM) caused a concentration-dependent presynaptic inhibition of stimulus-evoked cholinergic fast excitatory postsynaptic potential. Slow inhibitory post-synaptic potentials (sISPSs) were induced by focal electrical stimulation of the interganglionic fibre tracts in 43% of the neurones tested. Superfusion of both phentolamine (1 microM) and yohimbine (1 microM) reduced the sIPSPs while prazosin (1 microM) had no significant effect. We concluded that norepinephrine acted post- and presynaptically via alpha 2-adrenoreceptors to have an inhibitory effect on the guinea-pig colonic submucous. In addition, our study strongly supported the role of norepinephrine as a mediator of the sIPSPs. As a result, norepinephrine would primarily suppress information transfer within the neuronal circuits in guinea-pig colonic submucosal plexus.

Acetylcholine↗
PubMed1998

Discharge patterns of intramural mechanoreceptive afferents during selective distension of the cat's rectum.

The afferent input from the rectum to the central nervous system (CNS) has yet to be thoroughly characterized. The characteristics of mechanoreceptive rectal afferents have been studied in unanaesthetized decerebrate cats. Following lumbo-sacral laminectomy, single-unit activity (occasionally multi-unit activity) was recorded from centrally cut filaments of the sacral dorsal roots (predominantly S2), while a balloon was inflated in the rectum. Starting from their background activities (mean 15.1 imp sec-1, SD 7.6 imp sec-1), afferent discharge rate increased with increasing balloon pressure (mean threshold 6.3 mmHg, SD 3.6 mmHg). The dependence of firing rate on intrarectal pressure began to flatten out at 25 mmHg (mean; SD 10 mmHg). For 22 out of 29 units (76%) complete saturation occurred at 35 mmHg (mean; SD 15 mmHg) with a maximum discharge rate of 31 imp sec-1 (mean; SD 12.6 imp sec-1). In a number of recording sessions, cyclical rectal contractions were observed. In these cases, changes in firing of the units were closely related to changes in intrarectal pressure. Pressure-related afferent activity could be enhanced by parasympathomimetic drugs which augmented rectal contractions. We conclude that sacral dorsal roots contain afferents from low-threshold mechanoreceptors located in the rectal wall, and that these afferents monitor the filling state and contraction level of the rectum.

Animals↗
PubMed1998

Autonomic dysfunction in patients with achalasia of the oesophagus.

It has been suggested that achalasia is associated with extraoesophageal sympathetic and parasympathetic dysfunction. In a prospective study we applied conventional ultrasonography and duplex sonography to investigate basal and postprandial peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) of superior mesenteric artery and PSV of portal vein in nine patients with achalasia and 10 healthy controls (study I). In addition, in eight of these patients autonomic nervous function was investigated by pupillary function tests as well as cardiovascular reflex tests and compared with eight age- and sex-matched controls (study II). The results indicated that postprandial increase of PSV in the superior mesenteric artery was significantly lower, and postprandial decrease of PI and RI significantly higher in achalasia compared to healthy controls. In contrast, postprandial increase of PSV in the portal vein was not significantly different between both groups. Autonomic function tests revealed significant lower maximal pupillary contraction and redilatation velocities, significantly lower heart rate variation during orthostasis, deep respiration test and Valsalva manoeuvre in achalasia compared to controls. It is concluded that achalasia is associated with extraoesophageal autonomic nervous dysfunction that involves cardiovascular and pupillary function as well as regulation of mesenteric arterial blood flow.

Adult↗
PubMed1998

Transjugular intrahepatic portosystemic shunts: improved evaluation with echo-enhanced color Doppler sonography, power Doppler sonography, and spectral duplex sonography.

OBJECTIVE: We assessed the feasibility of contrast-enhanced color Doppler, power Doppler, and spectral duplex sonography for visualization and quantification of flow through transjugular intrahepatic portosystemic shunts (TIPS) in patients in whom the baseline sonographic evaluation was unsatisfactory. SUBJECTS AND METHODS: Thirty-three patients underwent color Doppler, power Doppler, and spectral duplex sonography after TIPS insertion or before TIPS revision (mean time interval +/- SD, 1 +/- 1 day). All sonograms were obtained before and after patients received echo-enhancing contrast material. Sonography was evaluated with regard to presence or absence of flow in the mid portion, portal segment, and hepatic segment of the shunt. The maximal peak velocity was measured in the mid portion of the shunt. For identifying and quantifying stenoses, the percentage of luminal diameter reduction was calculated at the tightest part of the shunt. Shunt angiography and measurements of portosystemic pressure gradients were independently evaluated and compared with the sonographic findings. RESULTS: Flow visualization on unenhanced color Doppler sonography was significantly improved through the use of power Doppler sonography and contrast-enhanced color Doppler and power Doppler sonography (p < .01). Between contrast-enhanced power Doppler and contrast-enhanced color Doppler sonography, a significant difference was found in the portal and hepatic segments (p < .05). All shunt stenoses (n = 8) and occlusions (n = 3) were revealed by power Doppler sonography, whereas color Doppler sonography failed to reveal six of eight stenoses. Compared with unenhanced sonography, the quality of spectral duplex sonography was improved in eight patients after contrast enhancement (p < .05). Maximal peak velocity ranged from 54 to 252 cm/sec (mean +/- SD, 132.7 +/- 52.1 cm/sec) in normal shunts and from 24.5 to 70.0 cm/sec (mean +/- SD, 45.0 +/- 18.9 cm/sec) in stenosed shunts. No correlation was found between maximal peak velocity and portosystemic pressure gradients (r = .28). CONCLUSION: Unenhanced power Doppler and contrast-enhanced color and power Doppler sonography can be helpful in the assessment of TIPS status in patients who previously underwent unsatisfactory sonography. These techniques may allow anatomic evaluation and quantification of shunt stenosis in most patients. Contrast enhancement may also considerably improve the quality of spectral duplex sonography.

Adult↗
PubMed1998

Postprandial changes of electrical activity of the stomach after different meals.

AIM: The aim of the study was to investigate the response of the electrical activity of the stomach (electrogastrogram, EGG) to meals, different with respect to consistency, nutrient and caloric composition. METHODS: EGG was recorded in ten healthy volunteers for 30 min before and 45 min after a meal. All subjects received three different meals: A standard 500 kcal solid, a 500 cc isocaloric liquid diet of identical composition (55% carbohydrates, 15% protein, 30% fat) or 500 cc water. Data were analyzed off-line for postprandial changes. RESULTS: Water as well as liquid diet induced a significant postprandial decrease, while solid food induced a slight initial decrease and a subsequent marked increase of the dominant frequency above the fasting level. The response to the solid meal was significantly different from both tap water and liquid diet, but there was no difference between liquid diet and water. All meals significantly increased the signal power with a more sustained effect over time for the liquid diet and water than the solid meal. CONCLUSION: EGG changes seem to be more dependent on the consistency than the caloric and nutrient composition. Because of the dissociation between the timing of EGG changes and the known emptying kinetics, EGG changes seem to reflect other gastric functions rather than being associated with gastric emptying.

Adult↗
PubMed1998

Neurogastroenterology--information processing from the viscera to the brain in humans.

With the many new investigational possibilities allowing access to the gut-brain axis in humans, new techniques, mainly from neurology, as well as interdisciplinary approaches, have produced insights into afferent information processing from the gut to the brain. They have become research tools in recent years, but will eventually become clinical tools for diagnostic purposes in the future. Gut-brain interactions may be seen at different levels: rather simple research models such as recordable perception and pain, on the one hand, can be contrasted and/or supplemented with neurological stimulation and imaging techniques, and clinical models such as spinal cord injury. All have contributed to the development of a new subspecialty in medicine, neurogastroenterology.

Brain↗