Effects of vacuum-assisted closure on central hemodynamics in a sternotomy wound model

Several authors have reported promising results with vacuum-assisted closure therapy in poststernotomy mediastinitis. The aim of this study was to investigate the hemodynamic outcome following the application of six negative pressures on an open sternotomy wound. Six 70-kg pigs underwent median sternotomy followed by vacuum-assisted closure therapy. Six negative pressures (-50, -75, -100, -125, -150, and -175mmHg) were applied to each pig for 30min each while hemodynamic parameters were measured. An increase in cardiac output was observed at -75mmHg when compared to the other five pressures: -50mmHg (P<0.05; CI 0.12-1.13l/min), -100mmHg (P<0.001; CI 0.34-1.32l/min), -125mmHg (P<0.001; CI 0.51-1.52l/min), -150mmHg (P<0.001; CI 0.50-1.47l/min), and -175mmHg (P<0.05; CI 0.13-1.17l/min). A decrease in systemic vascular resistance was observed at -75mmHg when compared to -125mmHg (P<0.01; CI 108-552dyn.s/cm(5)) and -150mmHg (P<0.01; CI 90-543dyn.s/cm(5)), but not compared to the other pressures. No change (P=ns) was observed in heart frequency, mean arterial pressure or central venous pressure. Our data demonstrates that vacuum-assisted closure therapy of -50 to -175mmHg does not impair the central hemodynamics in a porcine sternotomy model.     

Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in malays with malignant glioma

Recent advances in neuro-oncology have revealed different pathways of molecular oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal regions harboring tumor suppressor genes. In the present study, we performed polymerase chain reaction-loss of heterozygosity (PCR-LOH) analysis using microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%) cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma, three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one locus. Our findings showed that loss of heterozygosity on specific chromosomal regions contributes to the molecular pathway of glioma progression in Malay population. In addition, these data provide useful evidence of molecular genetic alterations of malignant glioma in South East Asian patients, particularly in the East Coast of Malaysia.     

Amphetamine enhances training-induced motor cortex plasticity

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.     

Long-term persistence of vaccination and HAART to human immunodeficiency virus (HIV)

The aim of this study was to monitor the immune responses in HIV-infected patients previously immunized with gp160 or DNA vaccines to analyze whether the introduction of highly active antiretroviral treatment (HAART) would affect the persistence of immunity. The immune responses were evaluated in patients who had participated in randomized trials of therapeutic vaccination. Immunization in conjunction with antiretroviral therapy was effective in inducing HIV-specific T-cell responses. Therapeutic immunizations with recombinant gp160 had a modest effect on CD4-cell counts, the treatment alone lead to a transient clinical benefit in the form of an improved survival after two years of immunization. Immunizations with HIV DNA during HAART treatment permitted persistence or development of innate (NK), CD4+ and/or CD8+ immune responses. HIV specific T-helper cell responses induced by immunization with gp160 were maintained at high levels up to 7 years after the last injection. Cells with HIV-specific interferon-gamma (IFN-gamma) production were retained or increased in long-term HAART treated patients. The impact of a single structured therapy interruption (STI) was analyzed in a small group of patients showing no obvious increase or decrease in the HIV-specific immune response during or after STI. The possibility to induce very long-term strong and persistent immune responses in HIV-infected individuals raises hopes that vaccination preceding therapy interruption might prolong the symptom-free period without HAART.     

Activity of hydrolytic enzymes in tumour cells is a determinant for anti-tumour efficacy of the melphalan containing prodrug J1

Recently, we presented a series of melphalan containing di- and tripeptides with high cytotoxic activity and J1 (l-melphalanyl-p-l-fluorophenylalanine ethyl ester) was identified as one of the most interesting compounds. It was speculated that the increased activity compared to melphalan itself, demonstrated both in vitro and in vivo, resided in increased transport over the tumour cell membrane and/or hydrolytic cleavage and liberation of melphalan inside the cells. Indeed, overexpression of hydrolytic enzymes like peptidases, esterases and proteases has been described in several types of human malignancies, thus providing a target for selective chemotherapy. In this work, the details of the increased activity was further investigated and potential tumour selectivity is discussed. The intracellular delivery of melphalan is investigated in detail using peptidase resistant dipeptide derivatives, by enzyme inhibitors and probes for enzymatic activity and by studying the time dependency of drug effect as well as intracellular drug concentrations (cellular pharmacokinetics). The results show that the activity of the dipeptide mustards is highly dependent on intracellular hydrolysis, which result in rapid intracellular release of the alkylating unit (i.e. free melphalan) in cells with high enzymatic activity. The maximum intracellular melphalan concentration following J1 exposure was reached already after 15 min, thereafter declining with a half-life of approximately 1 h. This rapid intracellular loading resulted in less reduction of activity for J1 than for melphalan and six other standard drugs when human tumour cell lines were exposed to the drugs for a limited time (simulating short half-life in vivo). Peptidase inhibitors inhibited the activity and intracellular release of melphalan, and dipeptide derivatives designed to resist the action of peptidases was less active than the corresponding normal dipeptide.     

Threshold vision in amblyopia: orientation and phase

PURPOSE: The visual deficit in amblyopia involves both elevated contrast thresholds and distorted suprathreshold percepts at high spatial frequencies. It is currently unclear whether these two anomalies are part of the same neural disturbance or whether they reflect different neural dysfunction. METHODS: The quality of the spatial percepts in amblyopia was assessed at detection threshold. The ability of amblyopes to discriminate the orientation and local spatial phase of well-localized spatial stimuli was measured at the detection threshold. Measurements were made as a function of spatial frequency. RESULTS: Performance seemed normal for orientation discrimination, even at high spatial frequencies, but, in some cases, it was disturbed in phase discrimination. CONCLUSIONS: A different explanation and neural basis is needed to encompass both threshold and suprathreshold spatial deficits in amblyopia.     

Adhesion of soluble fibronectin,vitronectin, and collagen type IV to intraocular lens materials

PURPOSE: To evaluate soluble fibronectin, vitronectin, and collagen type IV adhesion to poly(methyl methacrylate) (PMMA), fluorine-surface-modified PMMA, silicone, hydrophobic and hydrophilic acrylate, and hydrogel intraocular lenses (IOLs) and determine whether hydrophobic and hydrophilic acrylate materials have different fibronectin-adhesion properties. SETTING: Department of Medical Biochemistry, University of Oulu, Oulu, Finland. METHODS: One hundred fifty IOLs were incubated for 1 week at 37 degrees C with radioactive-iodine-labeled soluble fibronectin, vitronectin, or collagen type IV. Fifty IOLs were analyzed for each protein, 5 from each of 10 different IOL models (PMMA, Alcon MC60BM; fluorine-surface-modified PMMA, Chiron Fluorilens Centra-55F; silicone, Allergan Medical Optics SI-40NB and Pharmacia and Upjohn CeeOn 911A; hydrophobic soft acrylate, Alcon AcrySof MA60BM and SA30AL and AMO Sensar; hydrophilic soft acrylate, Ioltech Stabibag and Bausch and Lomb BL27; and hydrogel, Bausch and Lomb Hydroview. The amount of adherent protein was measured with a gamma counter at 1 and 7 days and expressed as counts per minute. RESULTS: At 1 week, significantly more fibronectin was bound to the hydrophobic acrylate IOLs than to the 2-hydroxyethyl methacrylate (HEMA) containing hydrophilic acrylate IOLs (P <.05 to.0001). Significantly more vitronectin was bound to the 2 silicone IOLs than to any other IOL (P <.01 to.0001) at 7 days. Collagen type IV adhered best to the hydrophilic acrylate IOLs, which were significantly different (P <.01 to.0001) than the other IOLs at 1 and 7 days. CONCLUSIONS: Each IOL material had a different affinity to each protein. Significant binding to 1 protein does not indicate that the IOL will bind significantly to all proteins; instead, each protein should be studied separately. Fibronectin bound significantly better to hydrophobic acrylate IOLs than to hydrophilic acrylate IOLs, suggesting that the HEMA-containing IOLs should be classified with the hydrogel IOL group.