Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.

BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.     

Uniportal vs standard three-port VATS technique for spontaneous pneumothorax: comparison of post-operative pain and residual paraesthesia.

OBJECTIVE: VATS using the conventional three ports is currently the technique of choice for blebectomy/bullectomy for spontaneous pneumothorax. However, the procedure has recently been shown to have neurological complications related to the port sites. Uniportal VATS has recently been proposed as an alternative to conventional three-port VATS. It is anticipated that the single incision will predispose to a lower incidence of neurological complications. METHODS: We report our initial single surgeon experience of uniportal VATS (n = 16) and provide a comparison of post-operative pain and residual paraesthesia to conventional three-port procedures (n = 19) for the same pathology. RESULTS: In both groups, the pneumothorax pathology was principally primary. There was no difference between the groups in terms of age, spirometry, tissue resected, drainage time and inpatient stay. A difference was, however, noted in inpatient pain scores. The uniportal group had a lower median score of 0.4 (visual analogue range 0-4) while the three-port technique reported 0.8 (P = 0.06, Mann-Whitney test). The maximum score trend was similar (1.4 vs. 2.6, respectively, P < 0.001, Mann-Whitney test). Follow-up for uniportal and three-port VATS averaged 9.4+/-6.6 and 32.1+/-9.9 months, respectively. One patient in the three-port group had a pneumothorax recurrence. Three-port VATS also had a higher residual pain score (0.5) compared to uniportal VATS (0.3). Of clinical significance was the incidence of neurological complications. Eighty-six percent of uniportal patients reported no symptoms. The remaining experienced only mild 'numbness' or 'swelling'. However, in the three-port group, only 42% reported no symptoms. A similar number experienced 'numbness'. Two females described sexual dysfunction due to altered breast sensitivity. Seventeen percent (2/12) reported 'pins and needles'. CONCLUSIONS: Uniportal VATS appears to be tolerable, safe and efficient in treating spontaneous pneumothorax in our series. Moreover, post-operative pain and paraesthesia incidence was lower than three-port VATS. Prospective randomised trials are important to evaluate this technique.     

Reconstruction of a transmetatarsal amputation stump using a salvaged peroneal artery fasciocutaneous flap from the opposite leg: A case report

During lower extremity amputation, the objective is to provide a functional residual limb that permits maximum patient mobility and independence. Preservation of length of the fore part of the foot using salvageable tissue from the amputated part in young patients prevents equines deformity and revision of amputation to a higher level. This can be achieved using tissue available from the amputated part. The spare part concept in reconstructive surgery should be integrated into the trauma algorithm to avoid additional donor site morbidity. Reported here is a young adult patient with crush injuries to both feet, which resulted in amputations. A fasciocutaneous flap raised from one extremity was used to facilitate transmetatarsal amputation stump length preservation of the other extremity.     

Immunomodulation in mice by Bacillus megaterium and its dependence on culture conditions

Mice pretreated with Bacillus megaterium ATCC 33085 grown on TSA medium developed a significant increase in primary antibody response to SRBC. Conversely, pretreatment with a spore suspension harvested from nutrient Agar medium decreased this antibody response. A suspension of organisms grown on a defined, phosphorus-deficient medium (P-Medium) had no effect. Otherwise, only the spore suspension was able to enhance the contact sensitivity to dinitrofluorobenzene. Peritoneal leucocyte numbers were increased by inoculation with both TSA-cultured bacteria and the spore suspension, but not by P-Medium-cultured bacteria. Administration of both the spore suspension and P-Medium-cultured bacteria decreased the in vitro phagocytosis by peritoneal adherent cells. These immunomodulator properties are discussed in relation to characteristics of the strain tested.     

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.