Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.     

Azide function and polyaddition: reaction of 2-azido-2,4,4-trimethylpentane and monoazidopoly(2-methylpropene) with some dienophiles

The 1,3-dipolar addition of 2-azido-2,4,4-trimethylpentane ( 1 ) to acetylene and ethylene derivatives such as phenylacetylene (2), acrylonitrile, diphenyl fumarate ( 4 ) and N,N′-methylenebis(1,4-phenylene)dimaleimide ( 8 ) leads to the corresponding triazole and triazoline derivatives. This study demonstrates that tertiary azides are able to react with dienophiles, and the application of this reaction for the synthesis of block copolymers was investigated with monoazido-telechelic poly(2-methylpropene) (PMP). It was shown that the azido group is stable under the severe conditions of the polycondensation reaction without decomposition (170°C, 24 h), and the monoadduct PMP- 8 is produced with acceptable yield.     

Analyses and perspectives in cancer immunotherapy.

Since the last two decades, rapid progress has been made in the field of cancer immunotherapy relevant to manipulation of adaptative cytotoxic T lymphocytes (CTLs) and innate immunity natural killer (NK) cells as well as antibodies. Many possibilities are now offered for therapeutic purposes contributing to better approaches in treatment of cancer.     

Interstitial fluids associated with wound repair support proliferation but not differentiation of neonatal rat myoblasts in vitro.

The ability of wound fluids to support events required for skeletal muscle regeneration was examined. Wound fluids were obtained from polyvinyl alcohol sponges 1, 3, 5, 10, and 15 days after implantation. Neonatal rat L8 myoblasts were used to test the ability of early wound fluids to promote myoblast proliferation and late wound fluids to promote myoblast differentiation-two characteristics deemed critical for effective skeletal muscle regeneration. Early wound fluids (1- and 3-day) stimulated DNA replication by myoblasts, as judged by tritiated thymidine uptake, up to ninefold (p < 0.05). Later wound fluids (5-, 10-, and 15-day) displayed decreasing ability to stimulate proliferation, with 15-day wound fluid failing to significantly stimulate proliferation. In contrast, myoblast differentiation, as judged by myotube fusion and creatine kinase activity, was progressively reduced by wound fluids of increasing age. In fact, late wound fluids (5, 10, and 15 days) reduced myotube fusion by 88% to 100% and depressed creatine kinase activity by 60% to 75% (p < 0.05). Thus, wound fluids from a repair environment appear to support myoblast proliferation early but suppress myoblast differentiation later. These characteristics suggest that the wound repair environment cannot fully support skeletal muscle regeneration.     

Elevated NMDA receptors in parkinsonian striatum.

Dopamine-glutamate interactions contribute to normal striatal function and have been implicated in neurotoxicity at nigrostriatal dopamine (DA) terminals. The present study examined the striata of idiopathic Parkinson's disease (PD) patients and age-matched controls for regional differences in the DA transporter and binding to N-methyl-D-aspartate (NMDA) receptors. [3H]Mazindol labeling of the DA transporter was reduced by 70-80% in the caudate and putamen of PD patients, with reductions being more extensive dorsally than ventrally. In contrast, L-[3H]glutamate binding to NDMA-sensitive receptors was 20-40% higher in PD cases than in controls. These findings raise the possibility that modifications occur within corticostriatal glutamate synapses of PD patients, possibly as a consequence of reduced nigrostriatal DA activity.     

Intra-operative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injection (SACI)

Background and aims Insulinomas are rare endocrine disorders. Pre-operatively, conventional imaging techniques often fail to localise the tumor. In addition, due to the lack of quick insulin assays, intra-operative confirmation of complete resection was impossible until recently. Materials and methods Six patients with biochemical evidence of an insulinoma underwent pre-operative localisation studies and selective arterial calcium injection (SACI). In addition, insulin was measured before surgery and every 10–15 min after resection of the tumor using a quick insulin assay. Results Pre-operative localisation studies identified the tumor correctly as follows: endosonography: three of four, magnetic resonance imaging: two of four and SACI: six of six. Tumors in the head and body were enucleated while those in the tail were resected (n = 2, each). Those three patients, in whom magnetic resonance imaging and/or endosonography could localise the tumors pre-operatively, underwent laparoscopic surgery while the remaining three patients underwent open surgery. Intra-operatively, insulin dropped to normal levels within 20 min in all cases. After a follow-up of 0.8–3 years, all patients remained biochemically cured. Conclusions Pre-operatively, SACI appears to be a very sensitive localisation technique and may be most helpful in guiding the surgeon if conventional imaging techniques fail to localise the tumor. Complete removal of an insulinoma can be reliably predicted using a quick insulin assay. This paper was presented at the 2nd Biennial Meeting of the European Society of Endocrine Surgeons (ESES), May 18–20, 2006, Krakow, Poland.     

Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.