Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex.

Recent studies put forward the idea that stimulus-evoked gamma-band oscillations (GBOs; 30-100 Hz) play a specific role in nociception. So far, evidence for the specificity of GBOs for nociception, their possible involvement in nociceptive sensory discriminatory abilities, and knowledge regarding their cortical sources is just starting to grow. To address these questions, we used electroencephalography (EEG) to record brain activity evoked by phasic nociceptive laser stimuli and tactile stimuli applied at different intensities to the right hand and foot of 12 healthy volunteers. The EEG was analyzed in the time domain to extract phase-locked event-related brain potentials (ERPs) and in three regions of interest in the time-frequency domain (delta/theta, 40-Hz gamma, 70-Hz gamma) to extract stimulus-evoked changes in the magnitude of non-phase-locked brain oscillations. Both nociceptive and tactile stimuli, matched with respect to subjective intensity, elicited phase locked ERPs of increasing amplitude with increasing stimulus intensity. In contrast, only nociceptive stimuli elicited a significant enhancement of GBOs (65-85 Hz, 150-230 ms after stimulus onset), whose magnitude encoded stimulus intensity, whereas tactile stimuli led to a GBO decrease. Following nociceptive hand stimulation, the topographical distribution of GBOs was maximal at contralateral electrode C3, whereas maximum activity following foot stimulation was recorded at the midline electrode Cz, compatible with generation of GBOs in the representations of the hand and foot of the primary sensorimotor cortex, respectively. The differential behavior of high-frequency GBOs and low-frequency 40-Hz GBOs is indicating different functional roles and regions in sensory processing.NEW & NOTEWORTHY Gamma-band oscillations show hand-foot somatotopy compatible with generation in primary sensorimotor cortex and are present following nociceptive but not tactile stimulation of the hand and foot in humans.

Interoceptive and multimodal functions of the operculo-insular cortex: tactile, nociceptive and vestibular representations.

The operculo-insular cortex has been termed the 'homeostatic control center' or 'general magnitude estimator' of the human mind. In this study, somatosensory, nociceptive and caloric vestibular stimuli were applied to reveal, whether there are mainly common, or possibly specific regions activated by one modality alone and whether lateralization effects, time pattern differences or influences of the aversive nature of the stimuli could be observed. Activation of the dorsal posterior insula was caused by all stimuli alike thus terming this area multimodal. Early phases of the noxious heat and caloric vestibular stimulation led to responses in the anterior insula. Using conjunction analyses we found that left- and right-sided tactile stimulation, but not nociceptive stimulation, caused a joint activation of the cytoarchitectonic area OP1 and nociceptive but not tactile stimulation of the anterior insula bilaterally. Tactile activation in the parietal operculum (SII, OP1) was distinct from nociceptive activation (OP3 and frontal operculum). The joint activation by all three stimuli located in the dorsal posterior insula argues for the presence of multisensory structures. The distinct activation of the anterior insula by aversive stimuli and the posterior insula by multisensory signals supports the concept of a partitioned insular cortex recently introduced based on connectivity studies and meta-analyses.

Pinprick-evoked brain potentials: a novel tool to assess central sensitization of nociceptive pathways in humans.

Although hyperalgesia to mechanical stimuli is a frequent sign in patients with inflammation or neuropathic pain, there is to date no objective electrophysiological measure for its evaluation in the clinical routine. Here we describe a technique for recording the electroencephalographic (EEG) responses elicited by mechanical stimulation with a flat-tip probe (diameter 0.25 mm, force 128 mN). Such probes activate Aδ nociceptors and are widely used to assess the presence of secondary hyperalgesia, a psychophysical correlate of sensitization in the nociceptive system. The corresponding pinprick-evoked potentials (PEPs) were recorded in 10 subjects during stimulation of the right and left hand dorsum before and after intradermal injection of capsaicin into the right hand and in 1 patient with a selective lesion of the right spinothalamic tract. PEPs in response to stimulation of normal skin were characterized by a vertex negative-positive (NP) complex, with N/P latencies and amplitudes of 111/245 ms and 3.5/11 µV, respectively. All subjects developed a robust capsaicin-induced increase in the pain elicited by pinprick stimulation of the secondary hyperalgesic area (+91.5%, P < 0.005). Such stimulation also resulted in a significant increase of the N-wave amplitude (+92.9%, P < 0.005), but not of the P wave (+6.6%, P = 0.61). In the patient, PEPs during stimulation of the hypoalgesic side were reduced. These results indicate that PEPs 1) reflect cortical activities triggered by somatosensory input transmitted in Aδ primary sensory afferents and spinothalamic projection neurons, 2) allow quantification of experimentally induced secondary mechanical hyperalgesia, and 3) have the potential to become a diagnostic tool to substantiate mechanical hyperalgesia in patients with presumed central sensitization.

[The artificial sphincter: therapy for faecal incontinence]. / Der künstliche Sphinkter zur Therapie der Stuhlinkontinenz.

INTRODUCTION: Faecal incontinence (FI) challenges a patient's professional, social and sexual life. Often the patient becomes depressive and socially isolated. If able to break open for therapy the patient should receive as first line a conservative treatment (like dietary measures, pelvic re-education, biofeedback, bulking agents, irrigation). DISCUSSION: When is the time to implant an artificial anal sphincter? If conservative therapy fails as well as surgical options (like a sphincteroplasty - if indicated a reconstruction of the pelvic floor if insufficient, or a sacral nerve stimulation) an ultimo surgical procedure should be offered to appropriate and compliant patients: an artificial anal sphincter. Worldwide, there are two established devices on the market: the artificial bowel sphincter® (ABS) from A. M. S. (Minnetonka, MN, USA) and the soft anal band® from A. M. I. (Feldkirch, Austria). How to implant the artificial anal sphincter? Both devices consist of a silicon cuff which can be filled with fluid. Under absolute aseptic conditions this cuff is placed in the lithotomy position by perianal incisions around the anal canal below the pelvic floor. A silicon tube connects the anal cuff with a reservoir (containing fluid) which is placed either behind the pubis bone in front of the bladder (ABS) or below the costal arch (anal band). With a pump placed in the scrotum/labia (ABS) or by pressing the balloon (anal band) in both types operated by the patient the fluid is shifted forth and back between the anal cuff and the reservoir closing or opening the anal canal. Both systems are placed completely subcutaneously. CONCLUSIONS: Both devices improve significantly the anal continence. Both systems have a high rate of reoperations. However, the causes for the redos are different. The ABS is associated with high infection and anal penetration rates of the cuff leading to an explantation rate to up to 60 % of the implants. This kind of complication seems to be much lower with the anal band. The major problem in the anal band is a defunctioning valve which occasionally has to be replaced. Despite these problems both types of artificial anal sphincters improve faecal incontinence significantly and, thus, quality of life of incontinent patients.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

[Nociceptive system : Nociceptors, fiber types, spinal pathways, and projection areas]. / Nozizeptives System : Nozizeptoren, Fasertypen, spinale Bahnen und Projektionsareale.

In order to transform a nociceptive stimulus into a painful perception, a highly specialized chain of structural and functional elements is necessary. This system comprises nociceptors in the periphery with specific molecular properties for differential coding of noxious submodalities, ascending and descending tracts that can control the input into the dorsal horn of the spinal cord as well as supraspinal processing that regulates the integration of nociceptive information with other sensory modalities and autonomic function. In this article, structures involved in nociceptive signal processing starting from the periphery up to spinal and cerebral structures are discussed in the order of their spatio-temporal activation sequence - as far as these are known. Already from the basis of the different receptor subtypes found on the thinly or unmyelinated nerve fibers in the periphery, the predominant principle of polymodality is demonstrated. Different input to the dorsal horn of the spinal cord by different nerve fiber populations to superficial and deep layers is explained, ascending tracts as well as descending systems capable of either facilitating or inhibiting the upstream flow of nociceptive information, together with their known transmitters. Finally, thalamic relay nuclei for sensory and nociceptive signals, as well as subcortical and cortical projection targets are discussed. To complete the current view of the nociceptive system, information from molecular biology and anatomic tracing studies as well as data from functional electrophysiologic cell recordings in animals and imaging studies in humans are assembled.

A cross-sectional investigation of discontinuation of self-injury and normalizing pain perception in patients with borderline personality disorder.

OBJECTIVE: Several studies have shown reduced pain perception in patients with borderline personality disorder (BPD) and current self-injurious behavior (SIB). The aim of the present study was to test whether pain perception in patients with current SIB is different from that of patients who had stopped SIB, and whether pain perception of the latter group differs from healthy controls (HC). METHOD: We investigated 24 borderline patients and 24 HC. Thirteen patients showed current SIB (BPD-SIB) and 11 patients did not exhibit SIB anymore (BPD-non-SIB). Pain thresholds were assessed using thermal stimuli and laser radiant heat pulses. RESULTS: We found significant linear trends for all pain measures. The BPD-SIB group was less sensitive than the BPD-non-SIB group and the latter were less sensitive than HC. The pain sensitivity negatively correlated with borderline symptom severity. CONCLUSION: The results suggest an association between the termination of SIB, decline of psychopathology and normalization of pain perception in borderline patients.

Combined EEG and MEG analysis of early somatosensory evoked activity in children and adolescents with focal epilepsies.

OBJECTIVE: The study aimed to evaluate differences between EEG and MEG analysis of early somatosensory evoked activity in patients with focal epilepsies in localizing eloquent areas of the somatosensory cortex. METHODS: Twenty-five patients (12 male, 13 female; age 4-25 years, mean 11.7 years) were included. Syndromes were classified as symptomatic in 17, idiopathic in 2 and cryptogenic in 6 cases. 10 patients presented with malformations of cortical development (MCD). 122 channel MEG and simultaneous 33-channel EEG were recorded during tactile stimulation of the thumb (sampling rate 769 Hz, band-pass 0.3-260 Hz). Forty-four hemispheres were analyzed. Hemispheres were classified as type I: normal (15), II: central structural lesion (16), III: no lesion, but central epileptic discharges (ED, 8), IV: lesion or ED outside the central region (5). Analysis of both sides including one normal and one type II or III hemisphere was possible in 15 patients. Recordings were repeated in 18 hemispheres overall. Averaged data segments were filtered (10-250 Hz) and analyzed off-line with BESA. Latencies and amplitudes of N20 and P30 were analyzed. A regional source was fitted for localizing S1 by MRI co-registration. Orientation of EEG N20 was calculated from a single dipole model. RESULTS: EEG and MEG lead to comparable good results in all normal hemispheres. Only EEG detected N20/P30 in 3 hemispheres of types II/III while MEG showed no signal. N20 dipoles had a more radial orientation in these cases. MEG added information in one hemisphere, when EEG source analysis of a clear N20 was not possible because of a low signal-to-noise ratio. Overall N20 dipoles had a more radial orientation in type II when compared to type I hemispheres (p=0.01). Further N20/P30 parameters (amplitudes, latencies, localization related to central sulcus) showed no significant differences between affected and normal hemispheres. Early somatosensory evoked activity was preserved within the visible lesion in 5 of the 10 patients with MCD. CONCLUSIONS: MEG should be combined with EEG when analyzing tactile evoked activities in hemispheres with a central structural lesion or ED focus. SIGNIFICANCE: At time, MEG analysis is frequently applied without simultaneous EEG. Our results clearly show that EEG may be superior under specific circumstances and combination is necessary when analyzing activity from anatomically altered cortex.

Hepatocyte proliferation and apoptosis in rat liver after liver injury.

BACKGROUND/AIMS: In this paper the early phase of proliferate response and apoptosis of hepatocytes after partial liver resection, during reperfusion after ischemia and during sepsis is demonstrated. METHODOLOGY: Experiments were conducted in a rat model with regeneration times of 0.5-24 hours after injury. Proliferation was analyzed by Ki-67 immunohistochemistry and confirmed by double staining with CK18 in FACS. Apoptosis was analyzed by TUNEL technique. RESULTS: Periportal hepatocytes enter the cell cycle already 0.5-2 hours after injury in all three models. This early proliferative response is predominant periportally localized. During reperfusion and during sepsis there was a strict pericentral apoptosis of hepatocytes found. CONCLUSIONS: An early periportal proliferation of hepatocytes is a common reaction of the liver to injury. This proliferation takes place much earlier then the main proliferative response 24-72 h after partial resection. This predominant periportal proliferation together with the pericentral apoptosis fit to the concept of the "streaming liver" in liver regeneration.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

OBJECTIVES: Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. METHODS: An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. RESULTS: LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 µV vs. 24.6 ± 1.7 µV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). CONCLUSION: The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors.

Cholestasis, metabolism and biliary lipid secretion during perfusion of rat liver with different bile salts.

The biological effects of bile acids depend largely upon their molecular structure. When bile acid uptake exceeds the maximal biliary secretory rate (SRm) cholestasis occurs. In order to characterize the influence of bile acid structure on its cholestatic potency we systematically studied SRm, maximal bile flow, maximal and cumulative phospholipid and cholesterol secretion with different taurine-conjugated tri-, di- and keto bile acids (Table I) in the isolated perfused rat liver. Bile acids with a high critical micellar concentration (CMC) promoted the greatest bile flow; a positive non-linear correlation between CMC and maximal bile flow was found. 3 alpha-Hydroxylated bile acids with a hydroxyl group in 6 alpha and/or 7 beta position and lacking a 12 alpha hydroxy group had a high SRm. SRm was not related to CMC or maximal bile flow, respectively. Phospholipids and cholesterol were secreted in a nearly fixed ratio of 12:1; a strong linear relationship could be observed. Cumulative phospholipid secretion over 48 min was significantly lower for non and poor micelle forming bile acids (TDHC and TUC) than for those with comparatively low CMC values (TUDC, TC, THC, THDC, TCDC) (70-140 vs. 210-450 nmol/g liver). At SRm all bile acids with good micelle forming properties showed a similar cumulative biliary lipid output. However, when biliary lipid output was related to 1 mumol bile acid secreted bile acids with a low SRm induced the highest lipid secretion (TCDC, TC). These data (1) demonstrate that a 6 alpha and/or a 7 beta hydroxy group on the steroid nucleus reduce cholestatic potency if the 12 alpha hydroxy group is absent, (2) suggest that in the case of micelle forming bile acids the total amount of phospholipids secreted in bile (depletion of cellular phospholipids) is associated with the occurrence of cholestasis whereby bile acids with a low SRm deplete the cellular phospholipid content at much lower bile acid concentrations than those with a higher SRm and (3) imply that bile acids with non and poor micelle forming properties (TDHC, TUC) presumably do not cause cholestasis (solely) by depletion of cellular phospholipids.

Colchicine inhibits taurodeoxycholate transport in pericentral but not in periportal hepatocytes.

Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.

Chemokines in human colorectal carcinoma.

BACKGROUND: Chemokines (CKs) may promote antitumor immunity in cancer, act as tumor growth factors, influence metastatic spreading or angiogenesis. The purpose of this study was to investigate whether CK expression is altered in colorectal carcinomas compared to normal mucosa and to elucidate its possible clinico-pathological implications. MATERIALS AND METHODS: The levels of CCL2 (MCP-1), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL 1 (GRO-alpha), CXCL 5 (ENA-78) and CXCL 8 (IL-8) were investigated in 10 colorectal carcinomas and their corresponding normal mucosa by the use of ELISA. RESULTS: All CK analyzed, with the exception of CCL5 (RANTES), were expressed at a significantly higher level in malignant tissue. CONCLUSION: Therapeutic studies in colon carcinomas should, therefore, focus more on the neutralization of CKs than on their application.

Effect of sleep deprivation on the electrophysiological signature of habituation to noxious laser stimuli.

BACKGROUND: Sleep deprivation induces hyperalgesia. However, this pro-nociceptive effect is not reflected at the electrophysiological level, since sleep restricted subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to explore the contribution of habituation to this paradoxical LEP amplitude decline. METHODS: We compared LEP's of 12 healthy students (23.2 ± 1.1 years) after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve repetitive laser stimulus blocks (each comprising twenty stimuli) were applied under three attention conditions ('focusing' - 'neutral' - 'distraction' condition). Stimulus blocks were split in part 1 (stimulus 1-10) and part 2 (stimulus 11-20). The contribution of habituation to the TSD-induced LEP amplitude decline was studied by calculating the percentage amplitude reduction of part 2 as compared to part 1. Individual sleepiness levels were correlated with (1) averaged LEP's and (2) the degree of habituation. RESULTS: TSD induced hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the attention condition, the P2 amplitude of the N2P2-complex was significantly reduced ('focusing': p = 0.004; 'neutral': p = 0.017; distraction: p = 0.71). Habituation of the P2 amplitude to radiant heat was increased after TSD ('focusing': p = 0.04; 'neutral': p < 0.001; distraction: p = 0.88). TSD had no significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of habituation (p = 0.14). CONCLUSION: TSD induces hyperalgesia and results in attention-dependent enhanced habituation of the P2 component. Increased habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude decline. For this article, a commentary is available at the Wiley Online Library.

Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

Abolished laser-evoked potentials and normal blink reflex in midlateral medullary infarction.

We investigated two patients presenting with the rare finding of almost isolated hemianalgesia with a sensory level on the contralateral side sparing the face. Clinical findings, electrophysiological studies (absent laser-evoked pain-related somatosensory potentials, normal electrically evoked somatosensory potentials, magnetically evoked potentials, and blink reflexes), and magnetic resonance imaging showed the ventrolateral medullar tegmentum containing the spinothalamic tract to be affected by lacunar infarction. The blink reflex R2 component was unimpaired in both patients.

The influence of ischemic bowel wall damage on translocation, inflammatory response, and clinical course.

BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.

The influence of portocaval shunting on inner ear structures.

In rats with a portocaval shunt the cells of the inner ear were examined in an ultrastructural study. In 15 rats a porto-caval shunt (PCS) was constructed. Control rats underwent identical procedures but no anastomosis was produced (SOP). The control rats were pair-feeded. PCS rats developed an increased urinary zinc excretion associated with weight loss, alopecia, lethargy and atrophy of the testes. The serum zinc concentration in PCS rats was significantly reduced. In the inner ear we found ultrastructurally an increasing number of lysosomes and a severe damage of the myelin sheath of the granular ganglion cells. The myelin sheath was split and filled with great myelin figures. In the outer hair cells resulted in an increasing number of lysosomes. In the stria vascularis and in Reissner's membrane a vacuolization of the tissue appeared. The results of this study show that rats with a porto-caval anastomosis serve as a pathophysiological model of zinc impoverishment like porto-caval shunting in patients with liver cirrhosis.

A stereological study of adrenocortical cells in spontaneously hypertensive rats (shr).

The ultrastructure of SHR (Spontaneously Hypertensive Rats) fasciculata cells was compared descriptively and quantitatively with that of nonstimulated fasciculata cells of Wistar rats using sterological methods. The volume and surface densities are expressed per cm3 of cytoplasm. The smooth endoplasmic reticulum in the SHR was significantly increased compared to the control animals (surface density : 28%, volume density: 35%). Mitochondria volume remained unchanged although the inner mitochondrial membranes were significantly reduced (37%). An attempt was made to draw up a relation between sterological and biochemical data of steroid synthesis within the fasciculata cell. A genetically determined enzymatic defect in the early steps of the transformation of cholesterol to pregnenolone may exist at the level of the inner mitochondrial membrane. Whether this altered steroid metabolism is important to the etiology of hypertension in the SHR requires further investigation.

Aminoterminal propeptide of type III procollagen: a marker of hepatic fibrosis after bile duct obstruction in the monkey.

BACKGROUND/AIMS: In an experimental study in monkeys, liver fibrosis development after segmental bile duct obstruction was investigated and correlated with the aminoterminal propeptide of type III procollagen (PIIINP). MATERIALS AND METHODS: Segmental bile duct obstruction was produced by ligation and section of the left hepatic bile duct in all monkeys. Fibrosis induction was examined by intravenous leukotriene C4 (LTC4, 5 nmol/kg) application, endogenous LT-production stimulated by endotoxin (LPS,salmonella abortus equi, 50 ng/kg), fibrosis inhibition by dexamethasone (1 mg/kg) intramuscularly and subsequent endogenous LT-production stimulation by LPS (50 ng/kg). Ligated and unligated liver lobe biopsies were taken 3, 7 and 12 weeks after ligation. All portal areas were measured morphometrically. PIIINP was measured by a specific radioimmunoassay each week and correlated with the morphometric results. RESULTS: Bile duct obstruction leads to secondary sclerosing cholangitis with bile duct vanishing and subsequent biliary cirrhosis combined with perivenous sclerosis and cavernous transformation of the terminal vein. The collagen concentration increased in the nonligated lobe from mean +/-SEM 1.05 +/- 0.03% to 1.53 +/- 0.19% only after LTC4 and with no difference in the other groups. In the ligated lobe collagen concentration increased significantly in all groups continuously from 1.05 +/- 0.03% up to: controls 6.1 +/- 0.9%, dexamethasone 5.9 +/- 0.8%, LPS 8.2 +/- 0.8%, LTC4 9.075 +/- 1.4%. PIIINP concentration rose within 6 weeks in the controls with hepatic bile duct obstruction from 34.43 +/- 15 ng/ml up to 57 +/- 13.27 ng/ml, after dexamethasone to 48.5 +/- 18.23 ng/ml, after LPS to 57 +/- 13.27 ng/ml, after LTC4 to 80.25 +/- 16.04 ng/ml. After 12 weeks, PIIINP decreased in the controls resp. after dexamethasone to 41.25 +/- 6.94 ng/ml resp. 33.5 +/- 7.72 ng/ml and increased after LPS resp. LTC4 up to 64.25 +/- 17.07 ng/ml resp.104 +/- 22.46 ng/ ml. The correlation of collagen deposition and PIIINP was in the controls r = 0.83, after dexamethasone r = 0.71, after LPS r = 0.83 after LTC4 r = 0.91. CONCLUSION: PIIINP determination after segmental bile duct obstruction correlates with collagen deposition and allows evaluation of hepatic fibrosis activity.