Subcortical neural synchrony and absolute thresholds predict frequency discrimination independently.

The neural mechanisms of pitch coding have been debated for more than a century. The two main mechanisms are coding based on the profiles of neural firing rates across auditory nerve fibers with different characteristic frequencies (place-rate coding), and coding based on the phase-locked temporal pattern of neural firing (temporal coding). Phase locking precision can be partly assessed by recording the frequency-following response (FFR), a scalp-recorded electrophysiological response that reflects synchronous activity in subcortical neurons. Although features of the FFR have been widely used as indices of pitch coding acuity, only a handful of studies have directly investigated the relation between the FFR and behavioral pitch judgments. Furthermore, the contribution of degraded neural synchrony (as indexed by the FFR) to the pitch perception impairments of older listeners and those with hearing loss is not well known. Here, the relation between the FFR and pure-tone frequency discrimination was investigated in listeners with a wide range of ages and absolute thresholds, to assess the respective contributions of subcortical neural synchrony and other age-related and hearing loss-related mechanisms to frequency discrimination performance. FFR measures of neural synchrony and absolute thresholds independently contributed to frequency discrimination performance. Age alone, i.e., once the effect of subcortical neural synchrony measures or absolute thresholds had been partialed out, did not contribute to frequency discrimination. Overall, the results suggest that frequency discrimination of pure tones may depend both on phase locking precision and on separate mechanisms affected in hearing loss.

Mechanism- and experience-based strategies to optimize treatment response to the capsaicin 8% cutaneous patch in patients with localized neuropathic pain.

The capsaicin 8% cutaneous patch is an emergent new treatment option for patients with peripheral neuropathic pain. In randomized controlled clinical studies relevant pain relief for 12 weeks was achieved in about one third of patients following a single application. The first part of this paper is a review of the pathophysiology, pharmacology, and published clinical trials with the capsaicin 8% cutaneous patch. The second part reports on outcomes of an interdisciplinary expert workshop, where new treatment results of three major German pain centers were presented and reviewed with the objectives of obtaining responder rates for different pain syndromes, assessing maintenance of effect under real-life conditions, and giving recommendations for practical care. The 12 week responder rates with pain relief of ≥ 30% were comparable in patients with mononeuropathies (37.9%) and postherpetic neuralgia (38.8%). Similar responder rates were seen in a subgroup of patients with cervical spine radiculopathy and back pain (46.7%). In HIV-associated neuropathy the responder rates were high (47.8%) but lower in patients with other polyneuropathies (17.6%). Response rates were nearly identical after 1 week (46.6%) and 4 weeks (43.3) and dropped only slightly at 12 weeks (37.4%). In a subgroup of 54 patients who underwent a second treatment, efficacy was maintained. Response rates in patients with or without lidocaine pretreatment were comparable. Treatment with the capsaicin 8% cutaneous patch was generally safe and well tolerated. The workshop panel recommended further investigation of opportunities to improve the application procedure and to perform studies on the skin penetration and distribution of capsaicin. A modified quantitative sensory testing (QST) should be developed for clinical practice in order to better understand the correlation of sensory profiles and response to capsaicin treatment.

Etiopathological aspects of achalasia: lessons learned with Hirschsprung's disease.

The etiology of primary esophageal achalasia is largely unknown. There is increasing evidence that genetic alterations might play an important but underestimated role. Current knowledge of the genetic base of Hirschsprung's disease in contrast is far more detailed. The two enteric neuropathies have several clinical features in common. This association may also exist on a cellular and molecular level. The aim of this review is to enlighten those etiopathogenetic concepts of Hirschsprung's disease that seem to be useful in uncovering the pathological processes causing achalasia. Three aspects are looked at: (i) the genetic base of Hirschsprung's disease, particularly its major susceptibility gene rearranged during transfection and its potential reference to achalasia; (ii) the altered motor functions in both conditions with loss of inhibitory innervation and interstitial cell pathology; and (iii) the involvement of these motility disorders in genetic syndromes.

[Achalasia in a patient with HIV/HCV coinfection: detection of HCV in the esophageal tissue]. / Achalasie bei HIV/HCV-Koinfektion : HCV-Nachweis im Ösophagusgewebe.

Esophageal involvement in the context of opportunistic infections in human immunodeficiency virus (HIV) positive patients is a frequent phenomenon. However, worldwide esophageal achalasia has been described only twice in HIV-infected patients.We report the case of a 44-year-old Caucasian patient with HIV and Hepatitis C virus (HIV/HCV) coinfection who, within 2.5 years, displayed a progressive symptomatology with dysphagia, retrosternal pain, regurgitation as well as a considerable loss of weight before achalasia was finally diagnosed. Treatment was performed primarily surgically by means of laparoscopic Heller myotomy with an anterior 180° semifundoplication according to Dor.Histopathology of the specimens taken from the lower esophageal sphincter high-pressure zone proved alterations with abundant connective tissue and only scarce parts of the smooth muscular system without inflammatory infiltrations. In addition, the ganglia cells of the myenteric plexus as well as the interstitial cells of Cajal were significantly reduced. Interestingly, specific gene sequences of the hepatitis C virus could be detected in the esophageal tissue specimen. In contrast, analysis of specific HIV-gene sequences in the same tissue revealed a negative result.The possible but previously unknown relationship between esophageal achalasia and coinfection with HIV and HCV, also described as neurotropic viruses, will be discussed.

[Success of treatment in higher stages of pain chronification as well? An evaluation of the Mainz pain staging system based on the QUAST-analysis sample]. / Behandlungserfolg auch bei höherer Schmerzchronifizierung? Eine Auswertung des Mainzer Stadienmodells auf Basis der QUAST-Analysestichprobe.

BACKGROUND: More than 10 years ago Gerbershagen gave a pessimistic prognosis for treatment success in patients with higher stages of pain chronification. To date only few studies concerning this statement exist and the results are inconsistent. The objective of this study was to evaluate the prognostic validity of the Mainz pain staging system (MPSS) in a large multicenter sample. It was assessed whether effects of treatment in patients with higher stages of pain chronification are less than those in other patients. Of further interest was whether treatment success is related to different outcome measures. METHODS: A total of 1,461 patients with the pain syndromes headache, neuropathic pain, back pain or algiomuscular pain and arthralgia were enrolled in the analysis. They were selected from the QUAST analysis sample which includes patients from 19 cooperating pain clinics. All patients had completed the German pain questionnaire prior to pain treatment and these data were compared with the last available questionnaire during the course of treatment. Outcome measures were pain intensity, psychological disability scores and patient global impression of success (PGIS). RESULTS: Analysis showed a significant improvement of all outcome measures in every MPSS stage. The greatest improvement was noted for pain intensity whereas outcome variables regarding mental health revealed the lowest improvement. Compared with patients with low pain chronification, changes in pain intensity were smaller for patients with the highest MPSS stage III but even in these patients the strength of effect was more than 0.80. About 50% of all patients showed a reduction of pain intensity of 2 or more points on an 11 point numerical rating scale and 46.6% of patients with a MPSS stage III showed this improvement. Importantly, PGIS was independent of the stage of chronification. Nearly 45% of all patients evaluated the treatment success as good or very good. CONCLUSIONS: According to the view of the patients, treatment in specialized pain centres is successful even in the highest stage of pain chronification. This notwithstanding, success of treatment must not be confounded with the efficacy of an intervention. It has to be noted that the results of the current study do not allow conclusions regarding efficacy of treatment.

[Characterization of chronic pain patients in German pain centers : core data from more than 10,000 patients]. / Patientenkollektiv deutscher schmerztherapeutischer Einrichtungen : Kerndaten von mehr als 10.000 Patienten.

BACKGROUND: In 1998 the board of the DGSS introduced a computerized documentation system named QUAST (quality assurance in pain therapy) building the foundation for a large, anonymous database that served as a data source for the statistical characterization of clinically relevant profiles of patients in German pain clinics. METHODS: A total of 10,054 data files collected between 1998 and 2004, including socio-demographic as well as psychometric and pain parameters were analyzed. RESULTS: The main pain diagnoses found in the database sample were back pain (37%), neuropathic pain (21.4%), soft tissue or arthralgia pain (19.5%) and headache (10.6%). The average duration of illness upon presentation at pain clinics was 7 years, nearly 20% contacted it within the first year. Of the sample, 43.8% of the patients were in the second chronicity stage and 39.0% in the third stage of the Mainz Pain Staging System (MPSS). Psychological measurements concerning despression, pain disability and quality of life indicated a great amount of psychological distress. Pronounced differences between main diagnostic groups were observed not only for psychological factors but also for direct pain parameters. CONCLUSIONS: The documented data differ from other population-based data collections. In contrast to common belief there are a considerable number of patients who find access to specialized pain therapy institutions at an early stage of their illness. The hitherto regular use of generic, syndrome-overlapping diagnosis and treatment tools should be reconsidered taking into account the differences found between the main pain diagnosis groups. Lastly, this analysis provides current data on the psychological state of chronic pain patients showing a high degree of psychological distress and underlying the need of psychotherapeutic interventions in the treatment of chronic pain patients.

Spontaneous splenic rupture, in tertian malaria.

We report a case of tertian malaria in a 36-year-old Caucasian male complicated by spontaneous splenic rupture 2 months after returning from Kenya. The ruptured and enlarged spleen displaying multiple subcapsular hemorrhages was surgically resected. Histological examination revealed a marked enlargement of the red pulp and a reduced white pulp in addition to hyperemia of the spleen. Tertian malaria was diagnosed by peripheral blood smear and elevated antibody titer against Plasmodium vivax. The patient underwent antimalarial therapy with chloroquine and primaquine and the further course was uneventful. Etiopathology, differential diagnosis and therapy of this rare complication in malaria are discussed.

Stable remission after administration of rituximab in a patient with primary hepatic marginal zone B-cell lymphoma.

We describe a case of primary hepatic marginal zone B-cell lymphoma in a 36-year-old Caucasian male with a history of chronic hepatitis B infection. Immunohistochemically, extensive infiltration by a CD20-positive, CD5- negative and CD10-negative lymphoid cell population displaying a follicular arrangement was detected. Molecular analysis of immunoglobulin heavy chain gene rearrangements confirmed the clonal expansion of lymphoma cells. Fourteen months after surgical treatment, the tumour recurred in close proximity to the liver hilus, hampering further surgery. Therefore, we implemented a therapy using the monoclonal anti-CD20-antibody rituximab in a dose of 375 mg/m(2), administered four times once a week. Six, 10, 18, and 26 months later the recurrent lymphoma could no longer be detected as shown by abdominal ultrasonography and CT. This case report demonstrates the difficulties of treating this extremely rare liver disease and shows its response to rituximab therapy.

[Validation of the German Mainz Pain Staging System in different pain syndromes]. / Validität des Mainzer Stadienmodells der Schmerzchronifizierung bei unterschiedlichen Schmerzdiagnosen.

OBJECTIVE: Our study was carried out to clarify whether differences in pain intensity,pain-related disability,depression and quality of life change with respect to the stage of chronicity of the Mainz Pain Staging Study (MPSS) in different pain syndromes. Keywords. METHODS: All patients with an initial pain clinic consultation from July 2000 to July 2001 and suffering from four major pain syndromes ("headache", "neuropathic pain", "back pain" or "muscle and joint pain") were included. Indicators of validity were several self-rating scales from the German pain questionnaire of the German Chapter of the International Association for the Study of Pain (DGSS). Patient data were collected using QUAST, a database environment specifically developed for documentation and quality assurance in pain therapy. An assessment was made for each of the four major diagnoses to determine whether patients in the three chronicity stages differed in their psychometric test results. In addition,the four diagnosis groups were tested for differences from one another. RESULTS: A total of 862 patient charts with documented pain syndromes and MPSS were extracted and analyzed. The extent of the subjective psychosocial stress and disability increased in all diagnosis groups and was correlated with the chronicity stage. The proportion of patients with an indication of clinically relevant depression (ADS score >23) increased with chronicity regardless of the pain diagnosis. The four main diagnosis groups differed with respect to the chronicity stage according to MPSS (P<0.001), with headache patients being classified predominantly as stage I. Patients with an additional pain diagnosis had a higher chronicity stage (P<0.001). CONCLUSION: Our results underline the validity of the MPSS for the four diagnosis groups examined; however, pain diagnosis must be controlled in all studies using chronicity stage as an independent variable, e.g., therapy studies. For optimal results physicians must closely follow the test instructions of the MPSS.

Signet-ring cell carcinoma of unknown primary location. Metastatic to lower back musculature - remission following FU/FA chemotherapy.

The detection of gastrointestinal signet-ring cell carcinoma by endoscopy can be a diagnostic challenge. The main clinical features include atypical metastasis and a poor prognosis. We present a case of a metastasizing signet-ring cell carcinoma with unknown primary location arising in 71-year-old female. Following 6 cycles of a routine intravenous FU/FA chemotherapy, an almost complete remission could be observed. After 2 years of follow up, metastatic recurrence was detected to the lower back musculature. This case report emphasizes the difficulties in diagnosing signet-ring cell carcinoma by endoscopy and demonstrates an unusual clinical course.

Costs of opioid therapy for chronic nonmalignant pain in Germany: an economic model comparing transdermal fentanyl (Durogesic) with controlled-release morphine.

The fentanyl transdermal therapeutic system (fentanyl-TTS;Durogesic) has a distinct route of administration and safety profile compared with other opioids used in the treatment of moderate to severe pain.These aspects are likely to have an impact on patient acceptance and functioning as well as efficacy. We compared the cost-utility of fentanyl-TTS and controlled-release morphine (cr-morphine) in the treatment of moderate to severe nonmalignant pain in outpatients in Germany. A 1-year, three-phased decisionanalytic model was constructed, incorporating estimates of a variety of aspects of pain control.Use of fentanyl-TTS was predicted to incur higher costs than cr-morphine over 1 year of treatment (DM 6950 vs.DM 6186, respectively) but was associated with a higher number of quality-adjusted life days (234 vs. 216, respectively), thus achieving an incremental cost-utility ratio of DM 15,960 per quality-adjusted life-year gained.The results of the decision-analytic model support the use of fentanyl-TTS as a favorable cost-effective option for the treatment of moderate to severe nonmalignant pain.

Influence of rate of change of frequency on the overall pitch of frequency-modulated tones.

The mechanism(s) determining pitch may assign less weight to portions of a sound where the frequency is changing rapidly. The present experiments explored the possible effect of this on the overall pitch of frequency-modulated sounds. Pitch matches were obtained between an adjustable unmodulated sinusoid and a sinusoidal carrier that was frequency modulated using a highly asymmetric function with the form of a repeating U or inverted U shaped function. The amplitude was constant during the 400-ms presentation time of each stimulus, except for 10-ms raised-cosine onset and offset ramps. In experiment 1, the carrier level was 50 dB SPL and the geometric mean of the instantaneous frequency of the modulated carrier, fc, was either 0.5, 1, 2, or 8 kHz. The modulation rate (fm) was 5, 10, or 20 Hz. The overall depth (maximum to minimum) of the FM was 8% of fc. For all carrier frequencies, the matched frequency was shifted away from the mean carrier frequency, downwards for the U shaped function stimuli and upwards for the repeated inverted U shaped function stimuli. The shift was typically slightly greater than 1% of fc, and did not vary markedly with fc. The effect of fm was small, but there was a trend for the shifts to decrease with increasing fm for fc = 0.5 kHz and to increase with increasing fm for fc = 2 kHz. In experiment 2, the carrier level was reduced to 20 dB SL and matches were obtained only for fc = 2 kHz. Shifts in matched frequency of about 1% were still observed, but the trend for the shifts to increase with increasing fm no longer occurred. In experiment 3, matches were obtained for a 4-kHz carrier at 50 dB SPL. Shifts of about 1% again occurred, which did not vary markedly with fm. The shifts in matched frequency observed in all three experiments are not predicted by models based on the amplitude- or intensity-weighted average of instantaneous frequency (EWAIF or IWAIF). The shifts (and the pitch shifts observed earlier for two-tone complexes and for stimuli with simultaneous AM and FM) are consistent with a model based on the assumption that the overall pitch of a frequency-modulated sound is determined from a weighted average of period estimates, with the weight attached to a given estimate being inversely related to the short-term rate of change of period and directly related to a compressive function of the amplitude.

Frequency modulation detection interference produced by asynchronous and nonsimultaneous interferers.

The effect of asynchronous and nonsimultaneous interferers on detection of sinusoidal frequency modulation (FM) was compared with the effect of a synchronous interferer. In a two-interval, two-alternative forced-choice (2I-2AFC) adaptive procedure, listeners had to detect FM with a modulation frequency of 15 Hz, imposed on a 1-kHz sinusoidal carrier (the target). The 200-ms target was presented either alone (baseline condition), or with an interferer whose timing relative to the target was varied. The interferer was a 2.3-kHz sinusoidal carrier which was also frequency modulated at a rate of 15 Hz. Experiment one showed that thresholds for detection of FM increased significantly, both with a synchronous FM interferer, and also with asynchronous interferers (starting 200 ms before and stopping 200 ms after the target). Moreover, "gapped" interferers that were turned off during presentation of the target (presented for 200 ms before and for 200 ms after the target but not simultaneously) produced the same significant increase in thresholds as an asynchronous interferer that was not interrupted. In contrast, thresholds were not affected by the presence of a gapped unmodulated sinusoidal interferer. Experiment two showed that increasing the duration of the silent gap (centered on presentation of the target) between FM interferers from 200 to 600 ms did not abolish the interference. Thus nonsimultaneous FM interferers produced frequency modulation detection interference (FMDI) even when the silent gap between the interferers and target clearly led to the interferers and target being perceived as separate auditory objects. A possible explanation for the findings is the existence of an asymmetry in perception of steady and modulated sounds, as recently proposed by Cusack and Carlyon [Br. J. Audiol. 34.2, 112 (2000)]. Alternative explanations in terms of ringing in a hypothetical modulation filter bank and adaptation seem unlikely.

In vitro dentinal surface reaction of 9.5% buffered hydrofluoric acid in repair of ceramic restorations: a scanning electron microscopic investigation.

STATEMENT OF PROBLEM: Fracture of porcelain is a relatively common clinical misfortune. Recent research has indicated that strong bonds can be formed between composite and dental porcelain. Porcelain surfaces are etched with hydrofluoric acid and treated with silane coupling agents before composite application. The question is how exposed dentin may react to etching with hydrofluoric acid. PURPOSE: This investigation examined the effect of 9.5% buffered hydrofluoric acid, of 36% o-phosphoric acid alone and in combination on the surface structure of cut human dentin. MATERIAL AND METHODS: Human molar teeth were sectioned in approximately 0.8-mm thick slices and treated with different acids or their combinations. Application periods were 10, 60, and 180 seconds. Specimens were processed for SEM and for energy-dispersive x-ray (EDX) microanalysis. RESULTS: The smear layer on the surface of sectioned dentin was not completely removed by hydrofluoric acid alone and that a dense amorphous precipitate was formed on the peritubular zone. Starlike structures in dentinal tubules were visible. EDX analysis revealed different fluoride content on the treated surface, dependent on the etchant used. CONCLUSION: Topical application of hydrofluoric acid appeared to provide a dentinal surface with an amorphous precipitate of fluoride. This layer may be important both for resistance of dental caries in dentin and for bonding reactions.

[Computer-assisted tool (QUAST) for documentation and quality assurance in pain treatment]. / QUAST Auswertungsorientiertes EDV-System zur Dokumentation und Qualitätssicherung in der Schmerztherapie.

BACKGROUND: In chronic pain patient's diagnostic and therapy planning many complex information must be evaluated and analysed. The variety of data cannot be mastered without assistance of a database tool adapted to these special need. DATABASE ENVIRONMENT: On the base of FileMaker Pro 5.0, a user-friendly and analysis-oriented database environment for documentation and quality assurance in pain therapy (QUAST) has been developed. QUAST has been tested for 2 years by 23 pain clinics in Germany including data of more than 14.000 patients. Among patients'demographic and clinical data all 335 fields of the validated German pain questionnaire are included in QUAST together with psychometric test procedures (CES, SES, PDI, SF-36). We developed a outcome questionnaire for the evaluation of treatment - related changes of outcome variables (103 fields), a daily questionnaire (11 fields) and a protocol to assess the effects of neural and other blockades (144 fields). All data of therapy and outcome can be documented (total number of the fields: 2661). The test results (e. g. in the form of total or compound scores) can be analysed and printed. For pain related diagnoses, procedures, blockades, drugs, expected and unexpected events hierarchical coding systems (altogether 72,157 data records) have been developed. These can be assigned automatically to coding systems like ICD-10 or ICP-M. CONCLUSION: Due to its ability of export into other databases and already enclosed routines QUAST permits an internal assurance of quality of process and outcome in pain management. It also can be an instrument of an external quality assurance. QUAST is at present the only computer system available in Germany, to fulfil the required prerequisites for adequate quality control.

Context dependence of fundamental-frequency discrimination: lateralized temporal fringes.

In a two-interval, two-alternative, forced-choice (2I-2AFC) adaptive procedure, listeners discriminated between the fundamental frequencies (F0s) of two 100-ms harmonic target complexes. This ability can be impaired substantially by the presence of another complex (the "fringe") immediately before and after each target complex. It has been shown that for the impairment to occur (i) target and fringes have to be in the same frequency region; (ii) if all harmonics of target and fringes are unresolved then they may differ in F0; otherwise, they have to be similar [C. Micheyl and R. P. Carlyon, J. Acoust. Soc. Am. 104, 3006-3018 (1998)]. These findings have been discussed in terms of information about the fringe's F0 being included in the estimate of the F0 of the target, and in terms of auditory streaming. The present study investigated the role of perceived location and ipsilateral versus contralateral presentation of the fringes on F0 discrimination of the target. Experiment 1 used interaural level differences (ILDs), and experiment 2 used interaural time differences (ITDs) to create a range of lateralized perceptions of the 200-ms harmonic fringes. Difference limens for the F0 of the monaural target complex were measured in the presence and absence of the fringes. The nominal F0 was 88 or 250 Hz and could be the same or different for target and fringes. Stimuli were bandpass filtered between 125-625, 1375-1875, or 3900-5400 Hz. In both experiments, the effect of the fringes was reduced when their subjective location differed from that of the target. This reduction depended on the resolvability of both the fringes and the target. The effect of the fringes was reduced most (but still present), when fringes were presented purely contralaterally to the target. The results are consistent with the idea that the fringes produce interference when the listeners have difficulty segregating the target from the fringes, and that a difference in perceived location enhances segregation of the sequentially presented stimuli.

Effects of ear of entry and perceived location of synchronous and asynchronous components on mistuning detection.

Listeners were required to detect mistuning imposed on the center ("target") component of a 200-ms complex consisting of the first seven harmonics of a 500-Hz fundamental. In the standard interval of each 2IFC trial, all components were frequency modulated in-phase by a 5-Hz sinusoid. In the signal interval the frequency modulation of the target component was inverted in-phase, thereby introducing a mistuning proportional to the depth of FM. In a similar experiment, using monaural presentation, Carlyon [J. Acoust. Soc. Am. 95, 2622-2630 (1994)] reported a substantial elevation of thresholds in the presence of an unmodulated asynchronous interferer with frequency identical to the mean frequency of the target. This was attributed to the interferer, causing the target component to be perceptually segregated from the remainder of the complex, thereby impairing across-frequency comparisons. Experiment 1 of the present study showed that an interferer presented contralaterally for 200 ms before and 100 ms after the signal complex (no simultaneous presentation) also impaired performance, but to a lesser extent than an ipsilaterally presented one. Experiment 2 showed that an interferer which was presented dichotically with an interaural level difference (ILD) of 10 dB, so that it was perceived contralaterally, had the same (large) effect as if it were presented ipsilaterally. Experiment 3 showed that, in the absence of any interferer, performance was impaired when the nontarget components were presented contralaterally to the target component. However, performance was not impaired when the nontarget components were presented dichotically with an ILD of 20 dB, so that they were perceived contralaterally to the target component. It is concluded that the level of performance in the mistuning task is determined by whether the target is presented to the same ear as the rest of the complex, rather than by its perceived location.

Human intestinal epithelial cells down-regulate IL-8 expression in human intestinal microvascular endothelial cells; role of transforming growth factor-beta 1 (TGF-beta1).

Cytokines produced from intestinal epithelial cells may function as signals to neighbouring immune cells. In the present study we analysed the effects of colonic epithelial cell lines (HT-29, Caco-2, HCT-116, Colo-320) and freshly isolated intestinal epithelial cells on IL-8 expression in the SV-40T transfected human microvascular endothelial cell line (HMEC-1). Epithelial cell-conditioned media and transwells preventing physical contact between epithelial and endothelial cells were used. TGF-beta1 and IL-8 levels were determined by ELISA and Northern blot analysis. Increasing concentrations of IL-1beta led to increasing production of IL-8. The addition of epithelial cell-conditioned medium or epithelial cells to HMEC-1 cells in a two-compartment co-culture system resulted in a strong decrease in IL-8 at the protein and mRNA level. Decrease of IL-8 was markedly stronger when epithelial cells were co-cultured in contact with HMEC-1 cells, indicating that not only soluble factor(s) play a role in the induction of IL-8 suppression in HMEC-1 cells. MoAbs against TGF-beta1 partially inhibited down-regulation of endothelial IL-8 expression. In further studies, IL-8 expression in freshly isolated human intestinal microvascular endothelial cells (HIMEC) was also down-regulated by intestinal epithelial cells. Our results demonstrate that intestinal epithelial cells down-regulate IL-8 expression in HMEC-1 cells. TGF-beta1 is a candidate factor of epithelial-endothelial communication in the colonic mucosa.