γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

Summary Recently we described a cutaneous T-cell lymphoma expressing the / T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating / T-lymphoma cells we established T-cell clones bearing the / T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these / T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of / T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-,since it was detectable in high amounts in the SN of these / T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN- antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-, which is secreted in high amounts from / T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.Abbreviations TCR T-cell receptor - IFN- interferon- - SN supernatant - placenta CM placenta conditioned medium - BM bone marrow - CFU-GM myeloid/monocyte colony formation - NK cells natural killer cells - Ab antibody M. Wilhelm was supported by theDeutsche Forschungsgemeinschaft (DFG Wi 728-2)     

A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 m thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08±1.10 m, 3.95±1.02 m, 5.04±1.56 m, and 6.11±2.23 m, the circumferences of those vessels seen as complete circles were 43.11±12.78 m, 43.71±12.87 m, 95.21±39.32 m, and 126.77±54.65 m; the lengths between vessel bifurcations were 13.28±3.08 m, 13.47±4.58 m, 24.91±9.66 m, and 41.82±28.08 m in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.     

Suppression of interleukin-1β- and tumor necrosis factor-·-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis

Background To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we investigated the alterations in the cytokine responses of peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in ulcerative colitis (UC) patients.Methods Twelve patients with UC who did not respond to steroid therapy were enrolled. Nine patients responded to LCAP therapy, but 3 patients did not show clinical improvement. PBMCs were isolated from peripheral venous blood obtained within 5min before and after the first and second session of LCAP treatment. Cells were stimulated with interleukin (IL)-1 and tumor necrosis factor (TNF)- for 24h, and the levels of secreted IL-8 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA).Results LCAP induced a significant decrease in peripheral lymphocyte, monocyte, and platelet counts. IL-1- and TNF--induced IL-8 and IL-6 secretion was significantly decreased after the first and second LCAP treatments. These responses were associated with inhibitory effects on nuclear factor (NF)-B DNA-binding activity.Conclusions LCAP downregulates the IL-1- and TNF--induced inflammatory responses in PBMCs isolated from UC patients. The induction of hyporesponsiveness to proinflammatory cytokines may be an important factor mediating the clinical effects of LCAP in UC patients.     

Inactivation of HIV in plasma derivatives by β-propiolactone and UV irradiation

Summary The inactivation of HIV in human plasma and plasma derivatives by combined treatment with -propiolactone and UV-irradiation was investigated. -propiolactone inactivated 3.5 log₁₀ and UV 2.8 log₁₀ HIV in plasma and -propiolactone 3.5 log₁₀ in cryoprecipitate and UV irradiation 4.5 log₁₀ in factor VIII concentrate.

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Inaktivierung von HIV in Plasmaderivaten durch -Propiolacton in Kombination mit UV-Bestrahlung

Zusammenfassung Untersucht wurde die Inaktivierung von HIV in humanem Plasma und Plasmaderivaten durch die kombinierte Behandlung mit -Propiolacton und UV-Bestrahlung. HIV wurde durch -Propiolacton um 3,5 log₁₀ und UV um 2,8 log₁₀ in Plasma und durch -Propiolacton um 3,5 log₁₀ in Kryopräzipitat bzw. durch UV um 4,5 log₁₀ in Faktor VIII-Konzentrat inaktiviert.

     

Bildgebung der Atemwege

Zusammenfassung Die Erkrankungen der Atemwege umfassen das gesamte sog. Leitungssystem, das vom Alveolarraum als sog. Austauschsystem unterschieden wird. Das Leitungssystem gliedert sich in die verschiedenen Abschnitte der oberen Atemwege inklusive Nasenhöhle, Pharynx und Larynx, die Trachea mit den zentralen Bronchien und den Bronchialbaum bis hin zu den Bronchiolen. Als Krankheitsursachen kommen extra- und intraluminale Prozesse in Frage, die kongenital, inflammatorisch, traumatisch, neoplastisch oder idiopathisch bedingt sein können. Je nach Lokalisation der Atemwegserkrankungen beeinflussen sie den Luftstrom bei In- und Exspiration. Der Befall der gesamten Strecke des Leitungssystems bis hin zu den small airways ist möglich. Daher sind auch die Veränderungen bei Asthma, Bronchiolitis, chronisch-obstruktiven und interstitiellen Lungenerkrankungen zu beachten. Die bildgebende Diagnostik umfasst Sonographie, Thoraxaufnahmen (Th) in 2 Ebenen, hoch auflösende (high resolution) Computertomographie (HRCT) mit Mehrzeilentechnik, im weiteren Sinne auch PET und MRT. Die Th in 2 Ebenen ist nach wie vor wegen ihrer ubiquitären Verfügbarkeit die bildgebende Basisuntersuchung, für eine exakte nichtinvasive Untersuchung des Thorax ist die HRCT heutzutage aber unerlässlich.     

Pyruvate carboxylase deficiencies: Complementation studies between “French” and “American” phenotypes in cultured fibroblasts

Pyruvate carboxylase (PC) deficiencies (McKusick 26615) are heterogeneous clinically and biochemically. We performed a complementation study with fibroblast strains from seven patients, (four patients with French phenotype, two patients with American phenotype, one patient with biotin responsive multiple carboxylase deficiency, MCD). The six isolated pyruvate carboxylase mutants (two cross-reacting material CRM –ve and four CRM +ve) failed to complement each other, but did complement a form of biotin responsive MCD.     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.     

Zur Epidemiologie und Ätiologie des Oesophaguscarcinoms in China

Ohne Zusammenfassung

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The epidemiology and etiology of esophageal cancer in China

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Stipendiaten der Alexander von Humboldt-Stiftung aus der Volksrepublik China

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The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangsloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

The treatment of hypertension: New lamps for old?

Summary Meta-analysis of clinical trials does not help the clinician to treat individual patients. A general conclusion that the reduction of high blood pressure is beneficial has to be matched by specific information about the level of blood pressure that is acceptable and about the effect of particular doses of specific drugs. Results obtained from trials of old-fashioned antihypertensive drugs cannot confidently be extrapolated to modern agents. Sufficient data do not exist to encourage universal drug treatment for patients with mild hypertension.     

Flexibility of erythrocytes in juvenile diabetes mellitus

Summary The rheological properties of erythrocytes of 47 diabetic children and adolescents were studied. Deformability of red cells of 32 patients under poor metabolic control was markedly decreased while the deformability of red cells of patients (15 individuals) under good control was normal. This diminished flexibility of erythrocytes of patients under poor control can be explained partly by an increased concentration of free fatty acids in plasma. Moreover we found a decreased fluidity of the intracellular hemoglobin caused possibly by a decreased concentration of 2, 3-diphosphoglycerate in the cells.Supported by Deutsche Forschungsgemeinschaft     

Detection of β-ureidopropionase deficiency with HPLC–electrospray tandem mass spectrometry and confirmation of the defect at the enzyme level

The pyrimidine bases uracil and thymine are degraded via the consecutive action of three enzymes to -alanine and -aminoisobutyric acid, respectively. To date, a number of patients have been described with a deficiency of dihydropyrimidine dehydrogenase and dihydropyrimidinase, the first two enzymes of the pyrimidine degradation pathway. In this study, we demonstrate that the first patient presenting with N-carbamyl--amino aciduria, due to a deficiency of -ureidopropionase, was easily diagnosed at the metabolite level using HPLC–tandem mass spectrometry. Urinary analysis showed strongly elevated levels of N-carbamyl--alanine and N-carbamyl--aminoisobutyric acid, with normal or moderately increased levels of the pyrimidine bases and the dihydropyrimidines, respectively. The deficiency of -ureidopropionase was confirmed by measuring all three enzymes of the pyrimidine degradation pathway. No activity of -ureidopropionase could be detected in a liver biopsy of the patient, while a normal activity of dihydropyrimidine dehydrogenase and dihydropyrimidinase was present. Thus, HPLC–tandem mass specrometry proved to be a powerful tool for the initial diagnosis of patients with deficiency of -ureidopropionase.     

Immunoglobulin production and secretion in bence jones protein myeloma and “nonsecretory” myeloma

Summary Using our electron microscopic method for polysome analysis and an immunofluorescent technique we studied Ig production and secretion by tumor cells in seven BJP myeloma patients and seven nonsecretory myeloma patients.In BJP myeloma Ig production and secretion is of three types: Type 1, only L-chains are synthesized and secreted; Type 2, the myeloma cells show fluorescence for H-chains, but upon polysome analysis there is no peak at polysomes corresponding to H-chain production; Type 3, the myeloma cells show fluorescence for H-chains, and polysome analysis shows two peaks corresponding to L- and H-chain production.Polysome analysis of nonsecretory myelomas show the presence of only very few membrane-bound polysomes and their distribution curves are entirely different from those of ordinary myeloma. Furthermore, the distribution patterns vary among seven cases. Results obtained by polysome analysis and immunofluorescent technique suggest that the nonsecretory myeloma could be divided into several subtypes.Supported in part by grants-in-aid for scientific Research (748103, 867050, 167092, 267108, 777124) from the Ministry of Education, Science and Culture of Japan     

Uptake and metabolism of radiolabelled GM1-ganglioside in skin fibroblasts from controls and patients with GM1-gangliosidosis

Summary The uptake and metabolism of [3-³H-sphingosine]GM1-ganglioside was measured in cultured skin fibroblasts from controls and patients with infantile, juvenile and adult GM1-gangliosidosis. When dissolved in medium with phosphatidylserine, GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A linear increase in GM1-ganglioside endocytosis was shown with phosphatidylserine concentrations of up to 40m/ml. A pulse-chase study revealed that [³H]GM1-ganglioside was metabolized to GM2-ganglioside, GM3-ganglioside, ceramide dihexoside, ceramide monohexoside, ceramide and sphingosine. Sphingosine was recycled to sphingomyelin. In a 20-h pulse study, cell lines from patients with GM1-gangliosidosis of infantile, juvenile and adult types hydrolysed 2–5%, 20–44% and 54–58% of the total endocytosed GM1-ganglioside respectively. These values were lower than in control cells (64.17 ± 5.43% (n=10)). The hydrolysis rates of exogenous [³H]GM1-ganglioside in cultured fibroblasts from patients with various types of GM1-gangliosidosis closely reflected the clinical severity.Abbreviations GM1 Gal13GalNAc14(NeuAc23)Gal14Galc-1-ceramide - GM2 GalNAc14(NeuAc23)Gal14Glc-1-ceramide - GM3 NeuAc23Gal14Glc-1-ceramide - CDH Gal14Glc-1-ceramide     

Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas

The production of the cytokines interferon (IFN ), interleukin-1 (IL-1 ) and tumor necrosis factor (TNF ) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significancy lower levels of IFN (P0.001), IL-2 (P0.001) and TNF (P0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN (P0.01), IL-2 (P0.001) and IL-1 (P0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN- levels, which was related to tumor burden.Abbreviations PHA phytohemagglutinin - PWM pokeweed mitogen - ELISA enzyme-linked immunoassay - IL interleukin - IFN interferon - TNF tumor necrosis factor, mAb, monoclonal antibody     

Comparing a high-dose dipyridamole SPECT imaging protocol with dobutamine and exercise stress testing protocols. Part III: Using dobutamine to determine lung-to-heart ratios, left ventricular dysfunction, and a potential viability marker

Determination of the severity of coronary artery disease (CAD) by single photon emission computed tomography (SPECT) imaging has previously been shown to have greater sensitivity, specificity, and accuracy when performed with pharmacologic stress using dobutamine than by standard dose dipyridamole (SDD) or exercise stress testing (EST) prior to SPECT imaging. The use of lung to heart (L:H) ratios has been shown to be valuable in determining the presence or absence of left main (LM) or triple vessel (3V) CAD. No such work has been previously reported for dobutamine. Twenty-one patients were studied using dobutamine (n=7) or EST (n=14). These results were compared with results from Part II of this series of studies using high-dose dipyridamole (HDD) pharmacologic stress. In this study, patients underwent L:H ratio analysis following injection of 3 mCi of Tl-201, this provides sufficient time for thallium clearance from the blood pool. Results of the L:H ratios were compared with the results of coronary arteriographic (CA) evaluation. Patients who were stressed via EST demonstrated statistically greater (p0.001) L:H ratios in patients with LM/3V CAD when compared with patients who had 0–2 significantly stenosed coronary arteries. Patients stressed with dobutamine demonstrated lower L:H ratios (p=NS) in patients with LM/3V CAD than was seen for patients with 0–2 V CAD. Patients stressed with dobutamine had statistically (p0.05) lower L:H ratios than did similar patients stressed with EST. Increased L:H ratios following EST and HDD, as shown previously in Part II of this series, provide excellent markers for LM/3V CAD following Tl-201 injection. The presence of normal L:H ratios in patients with LM/3V CAD following dobutamine stress may suggest the presence of stunned or hibernating myocardium. The presence of decreased L:H ratios following dobutamine after HDD or EST has already shown an increased L:H ratio, might suggest a marker for myocardial viability that deserves further investigation.Presented in part at the 39th Annual World Congress International College of Angiology, Istanbul, Turkey, June 1997.     

Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

The Role of Pleural Fluid-Serum Gradient of Tumor Necrosis Factor-α Concentration in Discrimination Between Complicated and Uncomplicated Parapneumonic Effusion

In a previous preliminary study an excess of tumor necrosis factor- (TNF) was found in pleural fluid of patients with complicated parapneumonic effusion (CPPE), and its levels in pleural fluid of these patients were shown to be significantly higher than those in patients with uncomplicated parapneumonic effusion (UCPPE). This larger population study was undertaken to investigate, for the first time, the role of pleural fluid-serum gradient of TNF (TNFgradient) in discrimination between UCPPE and CPPE. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in serum and pleural fluid of 51 patients with UCPPE and 30 patients with nonempyemic CPPE. The mean±SEM values of serum TNF (TNFserum), pleural fluid TNF (TNFpf), and TNFgradient in the UCPPE group were 6.65±0.48 pg/mL, 10.85±0.74 pg/mL, and 4.2±0.38 pg/mL respectively, and in the CPPE group they were 7.59±0.87 pg/mL, 54.02±5.43 pg/mL, and 46.43±5.34 pg/mL, respectively. While no significant difference was found between the two groups regarding levels of TNFserum (p=0.31), a highly significant difference between these two groups was found regarding levels of TNFpf and TNFgradient (p < 0.0001 for both variables). A significant correlation was found between levels of TNFserum and levels of TNFpf in the UCPPE group (r=0.89, p < 0.0001), but not in the CPPE group (r=0.18, p < 0.33). TNFgradient at an optimal cut-off level of 9.0 pg/mL was found to be a good marker for discrimination between UCPPE and CPPE (sensitivity, 96.7%, specificity, 98%, accuracy, 97.5%, and p < 0.0001). In conclusion, levels of TNFpf but not TNFserum are significantly higher in CPPEs than those in UCPPEs where TNFgradient at an optimal cut-off level of 9.0 pg/mL is a good marker for discrimination between UCPPE and CPPE.     

Coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomas

We attempted to examine the correlation between matrilysin and laminin-5 2 chain expression with reference to the number of dedifferentiation units along the entire invasive front (tumor budding). Immunostaining for hMMP-7 and laminin-5 2 chain was performed in 50 T1 colorectal carcinomas, and immunoreactivity was evaluated at the invasive front of the tumor. On hematoxylin–eosin sections, the number of tumor budding was counted. The localization of matrilysin tended to be widespread compared with that of laminin-5 2 chain. Matrilysin and laminin-5 2 chain expression were positive in 28 (56%) and 15 (30%) tumors respectively. There was a significant correlation between matrilysin and laminin-5 2 chain expression (P = 0.02). Matrilysin(+)/laminin-5 2 chain(+) tumors had a significantly greater amount of tumor budding than matrilysin(–)/laminin-5 2 chain(–) tumors (P = 0.003) or matrilysin(+)/laminin-5 2 chain(–) tumors (P = 0.03). In conclusions, coexpression of matrilysin and laminin-5 2 chain may contribute to tumor cell migration in colorectal carcinomas.     

Down-regulated β-adrenoceptors in severely failing human ventricles: Uniform regional distribution,but no increased internalization

Summary In chronic heart failure cardiac -adrenoceptors are decreased. In this study we investigated whether a) in severely failing human ventricles -adrenoceptors are uniformly decreased or regional variations exist, and b) the -adrenoceptor decrease is caused by increased internalization or is a real loss in -adrenoceptors. For this purpose we assessed -adrenoceptor number and subtype distribution in a particulate fraction (mainly sarcolemmal plasma membranes) and a light vesicle fraction of right and left ventricular segments (obtained by cutting transversal, rings of 2 cm from the midventricular regions) of explanted hearts from 2 patients with end-stage congestive dilated cardiomyopathy (DCM) and one patient with end-stage ischemic cardiomyopathy (ICM). In all three hearts ventricular -adrenoceptor number was very low (7.5–10 and 21–26 fmol/mg protein in DCM, 15–22 fmol/mg protein in ICM compared to 68–74 fmol/mg protein in non-failing ventricles). -Adrenoceptors were uniformly decreased over the whole ventricular region and no considerable regional variations existed. The same held true for ₁- and ₂-adrenoceptors. In ICM decrease in -adrenoceptors was due to a concomitant reduction in ₁- and ₂-adrenoceptors, in DCM it was mainly caused by ₁-adrenoceptor down-regulation. In all ventricular segments investigated light vesicle -adrenoceptors amounted to about 5–7% of total ventricular -adrenoceptors and this was not significantly different from non-failing left ventricles. We conclude that a) in severely failing human ventricles -adrenoceptors are evenly down-regulated and no regional variations exist and b) the decrease in -adrenoceptors is not due to enhanced internalization but is a real loss of -adrenoceptors.Abbreviations DCM dillted cardiomyopathy - ICM ischemic cardiomyopathy - ICI 118,551 erythro-(±)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydrochloride - CGP 12177 (±)-4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole-2-on hydrochloride - ICYP (–) [¹²⁵I]-Iodocyanopindolol     

The flow-function relationship in patients with chronic coronary artery disease and reduced regional function: a Doppler transesophageal and bidimensional transthoracic echocardiography study

Background: Infra-low dose dipyridamole allows one to selectively explore myocardial viability. Transesophageal echocardiography Doppler measurement of left anterior descending coronary artery flow at baseline and following dipyridamole is an efficient tool to assess coronary flow response. Aim of this study was to determine the flow-function relationship during coronary vasodilatory stress in patients with coronary artery disease and baseline dysfunction. Methods and results: Twelve patients with resting dyssynergies and 6 controls underwent assessment of regional function and of left anterior descending blood flow velocity. Flow and function were evaluated at rest and following infra-low dose dipyridamole (0.28mg/Kg over 4min). Controls showed a normal function at rest and after dipyridamole. Six patients (Responders) with resting dyssynergies showed an improvement in segments of left anterior descending artery territory, whereas the other six ones (Non-responders) showed no functional change. Controls and Responders had similar values of resting peak diastolic left anterior descending artery flow velocity both at rest and after dipyridamole, whereas Non-responders showed a blunted flow response to dipyridamole. Conclusion: Myocardial segments with a resting dysfunction and a contractile reserve more often exhibit a residual flow response, whereas segments with fixed pattern show a flat flow response during coronary vasodilator stress.