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.     

Journal at the shelter

A Vietnamese social work and youth studies student describes her experiences and her feelings as a volunteer intern in an urban shelter program for children and youth in the United States.     

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.     

Fetal heart rate and umbilical artery flow velocity variability in intrauterine growth restriction: a matched controlled study.

OBJECTIVES: To study heart rate and umbilical artery blood flow velocity variability in growth-restricted fetuses and investigate the influence of the autonomic nervous system on these parameters. METHODS: Doppler velocity waveforms were collected from long-lasting umbilical artery recordings in 15 fetuses with growth restriction and 15 normal age-matched controls at 23-35 weeks of gestation. Absolute heart rate and umbilical artery blood flow velocity as well as the coefficient of variation were determined. Using power spectral analysis the low- and high-frequency bands of heart rate variability and blood flow velocity variability were calculated. The low-to-high (LH) ratio of heart rate variability and blood flow velocity variability were examined as a measure of sympathovagal balance. RESULTS: In growth-restricted fetuses umbilical artery velocities were significantly reduced. Heart rate variability was significantly reduced in the presence of growth restriction, but no significant difference was demonstrated for blood flow velocity variability. The LH ratio for heart rate variability was significantly decreased in growth restriction, but no difference in LH ratio was demonstrated for blood flow velocity variability. CONCLUSION: Flow velocity variability in growth restriction seems not to be predominantly influenced by the autonomic nervous system, whereas the decreased heart rate variability seems to be influenced by altered sympathetic-parasympathetic balance.     

Cardinal points and image–object magnification with an accommodative lens implant (1 CU)

A simple mathematical method for the determination of the cardinal points of pseudophakic eyes after implantation of an accommodative intraocular lens [posterior chamber intraocular lenses (PCIOL)] is presented. The purpose of this study was to explore the changes during pseudophakic accommodation (PAC) in (1). the positions of the cardinal points, (2). the distance of the object conjugate with the retina, and (3). the image-object magnification. These theoretical accommodation data are compared with clinical measurements. METHODS AND PATIENTS: Using biometrical measurements of the axial length, equivalent power of the cornea and the anterior chamber depth (ACD) in the non-accommodated state we used linear geometric optics for determination of the cardinal points and object distance as well as lateral magnification (the ratio of image to object size). With the measurement of ACD decrease (following pharmacological stimulation of the ciliary muscle with 2% pilocarpine eye drops) we determined the changes of the cardinal points and magnification to assess PAC amplitude from the shortening of the object distance. Calculated values of PAC amplitude were compared with the respective measured values derived from amplitude measures by accommodometer, defocusing and streak retinoscopy. We analysed the results of a prospective study on 35 eyes of 28 patients after cataract surgery (target refraction: -0.2 D) and accommodative PCIOL implantation (1 CU, Human Optics AG, Erlangen, Germany) 3 months after surgery. RESULTS: After pilocarpine eye drops, ACD (mean +/- S.D., range; median) decreased by 0.88 +/- 0.48 mm (0.51-1.91; 0.66). Distance of the in-focus object decreased from the non-accommodated state (-5.62 +/- 1.83 m, -25 to -1.1; -4.83 m) to the accommodated state (ACD decrease) (-0.81 +/- 0.21, -2.11 to -0.65; -0.79 m). For a theoretical ACD decrease of 1.0 mm (the intrinsic limitation of the PCIOL design) it was -0.59 +/- 0.28, -1.31 to -0.51; -0.63 m and resulted in an objective accommodative response of 1.49 +/- 0.16, 1.21-1.81; 1.46 D, depending on the actual geometry of the individual eye. On average, magnification as induced by PAC in contrast to that induced by adequate spectacle addition differed by only about 1%. Accommodation measured with defocusing and the accommodometer correlated significantly with the theoretical value based on IOLMaster measurement of ACD decrease (r = 0.752, p = 0.005 and r = 0.676, p = 0.02). Likewise, accommodation measured with streak retinoscopy correlated weakly with the theoretical value based on IOLMaster ACD decrease (r = 0.465, p = 0.05). CONCLUSIONS: Using geometrical optics, PAC can be derived from the biometric data of the eye and the measured ACD decrease. This approach may be an additional indicator for the accommodative response in pseudophakic patients and may allow a subdivision of the measured accommodation into true PAC and pseudoaccommodation, for example, because of increased depth of focus induced by pupillary constriction.