Preimplantation retrograde pneumoplegia in clinical lung transplantation.

OBJECTIVE: Retrograde pneumoplegia seems to improve early graft function in experimental and clinical lung transplantation. We evaluated the role of retrograde flushing in addition to antegrade pneumoplegia in clinical lung transplantation. METHODS: Fourteen patients undergoing lung transplantation were randomized into 2 groups: in group I we performed antegrade pulmonary artery flushing with alprostadil (prostaglandin E1) and modified Euro-Collins solution at the time of retrieval. In group II additional retrograde flushing through the pulmonary veins was performed at the back table, before reimplantation. Hemodynamic variables, mean airway pressure, and blood gas analysis were monitored at different time points. Postoperative volumetric monitoring was performed to assess extravascular lung water. The reimplantation response was assessed by a radiographic score; extubation time and intensive care unit stay were recorded. RESULTS: During retrograde flushing, blood and clots coming out from the pulmonary artery were observed; 2 lungs harvested from a donor with multiple bone fractures had fat emboli in the retrograde perfusate. Hemodynamic monitoring did not demonstrate any difference between the 2 groups. The ratio of arterial oxygen tension to inspired oxygen fraction, extravascular lung water, duration of intubation, and length of stay in the intensive care unit were improved in group II, but the differences did not reach statistical significance. Intrapulmonary shunt fraction was significantly improved in group II at each time point ( P =.02), as well as indexed alveolar-arterial oxygen tension gradient (P =.04), mean airway pressure (P =.04), and chest x-ray score ( P =.03). CONCLUSIONS: Preimplantation retrograde flushing is not detrimental and helps to improve early graft function.     

Necrotizing fasciitis. A diagnostic and therapeutic challenge

A case of necrotizing fasciitis of the upper limb caused by group A streptococcal infection and a case with an abscess of the hand caused by staphylococcus aureus, are presented. The anatomo-pathological and clinical differences between the two different types of infection are underlined and stress is laid on the excruciating pain, the high temperature and the rapidly spreading inflammatory-necrotizing evolution of the first case. More than the anatomo-pathological findings of a necrotic area the authors consider more important, the rapidity and the severity of the infection, that can evolve into a toxic shock-like syndrome, and the microbiological isolation of the streptococcus type A. On the basis of personal experience and of an accurate review of the literature, a therapeutical protocol is proposed based on an aggressive surgical approach, prompt specific antibiotic treatment and daily control of the lesions.     

A study on the role of the family and other risk factors in HCV transmission

Background/aims: To understand the intrafamilial transmission and the existing risk factors related to HCV infection in subjects confirmed anti-HCV positive, their sexual partners and household contacts in Friuli, North-East Italy. Methods: We enrolled all the subjects that were consecutively identified as HCV positive during routine laboratory testing in six health districts and their household contacts. From each subject we obtained a blood sample, demographic data and a medical history including the existence of risk factors for HCV. Antibodies to HCV were detected employing a commercially available second-generation enzyme immunoassay (EIA); positive serum specimens were retested using a second-generation recombinant immunoblot assay (RIBA-2). Results: We recruited 743 subjects, 229 first subjects identified as HCV positive and 514 household contacts. There were no statistically significant differences in positivity among household contacts. Analysing intracouple transmission we found no significant differences by gender in couples both with and without parenteral risk factors. We found, both with univariate and multivariate analysis, as statistically significant risk factors in all the subjects: age older than 60, blood transfusions (particularly those performed before 1984), surgical procedures such as abortion and/or uterine curettage, history of HBV infection, intravenous drug use, and tattooing. Conclusions: Our results stress the low relevance of sexual transmission in the intrafamilial context, the importance of abortion and/or uterine curettage, the important role of blood transfusions in the past, a higher prevalence of HCV infection within a household of a HCV positive member compared to all other existing data in the area.     

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p=0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

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Sommario Al fine di analizzare il fenomeno della normalizzazione della pressione arteriosa dopo ictus cerebrale in pazienti prima ipertesi, abbiamo osservato 107 soggetti con primo ictus ischemico, che erano già precedentemente affetti da ipertensione arteriosa da almeno un anno. Degli 82 (77%) sopravvissuti a tre mesi di follow-up, 44 (54%) hanno mostrato una normalizzazione della pressione arteriosa. L'incidenza di fattori di rischio per malattia cerebrovascolare e disabilità grave non è risultata significativamente diversa nel gruppo degli ipertesi rispetto ai normotesi. Tuttavia la normalizzazione della pressione arteriosa è stata osservata in 34 dei 54 pazienti con ictus carotideo (63%) e solo in 10 dei 28 con ictus vertebrobasilare (36%) (p=0.035). Riteniamo che tali dati offrano uno spunto per ulteriori ricerche sulla genesi neurogena dell'ipertensione arteriosa essenziale.

     

Bispecific monoclonal antibodies directed to CD16 and to a tumor-associated antigen induce target-cell lysis by resting NK cells and by a subset of NK clones.

CD16 surface antigens represent activatory molecules in CD3-16+ NK cells. In order to target NK cells against relatively NK-resistant ovarian carcinomas, we used an anti-CD16 monoclonal antibody (MAb) (VD4), together with an anti-ovarian carcinoma-associated antigen (MOV19), to construct biMAbs. To this end, hybrid hybridomas were generated by fusing a TK-deficient VD4 hybridoma mutant with a HGPRT-deficient MOV19 hybrid. Supernatants from hybrid hybridomas that had been selected in HAT medium were screened for their ability to induce a CD3-16+ NK clone to lyse an MOV19+ ovarian carcinoma cell line in a 4-hr 51Cr-release assay. The NMB.45 hybrid hybridoma secreted a biMAb which triggered lysis of MOV19+ but not of MOV19- target cells. Some degree of target cell lysis was also observed with MOV19 MAb (due to ADCC mechanisms), while the VD4 MAb was ineffective. HPLC fractionation of MAbs secreted by the hybrid hybridoma made it possible to identify 4 different peaks, one of which appeared to contain functional biMAb molecules. HPLC-purified biMAb (100 ng/ml) induced resting PBL to lyse the "NK-resistant" IGROVI ovarian carcinoma cell line. Fresh MOV19+ tumor cells were also lysed, although with lower efficiency. When IL-2-activated lymphocytes were used as a source of effectors, biMAb caused only minor increases in the IL-2-induced cytolytic activity. Further analyses of the effect of biMAb were performed at the clonal level. Among CD3-16+ NK cell clones, a clear enhancing effect could be observed only in GL183+ but not in GL183- clones. In CD3+ cytotoxic clones a triggering effect could be detected in one out of 4 TCR gamma/delta+ clones but not in TCR alpha/beta+ clones.     

Negative interaction of aspirin and streptokinase in acute ischemic stroke: further analysis of the Multicenter Acute Stroke Trial-Italy

BACKGROUND: Thrombolytic therapy improves the functional outcome in acute ischemic stroke, but the risk of death and cerebral hemorrhage remains high. Aspirin given together with a thrombolytic agent may worsen the risk-to-benefit ratio. We performed a further Multicenter Acute Stroke Trial-Italy (MAST-I) which is the only randomized, controlled trial that has tested the effect of this combination to evaluate the risk of aspirin use plus streptokinase. Patients and METHODS: We made a post hoc analysis of the MAST-I results comparing streptokinase plus aspirin (156 patients) with streptokinase alone (157 patients). We evaluated the risk of death and cerebral hemorrhage. RESULTS: The combined regimen significantly increased early case fatality from day 3-10 (53 vs. 30; OR 2.1; CI 1.2-3.6). The death excess was solely due to treatments and was not explained by the main prognostic predictors (multifactorial analysis). The cause of death in the combination group was mainly cerebral (42 vs. 24; OR 2.0; CI 1.3-3.7) and associated with hemorrhagic transformation (22 vs. 11; OR 2.2; CI 1.0-5.0). The rate of stroke reoccurrence was not increased in patients treated with streptokinase alone (15 vs. 11; OR 1.4; CI 0.6-3.4). CONCLUSIONS: Stroke patients treated with streptokinase plus aspirin have an increased risk of early death, probably due to cerebral hemorrhagic complications. Whenever thrombolytics are chosen for acute stroke treatment, aspirin and other antiplatelet agents should be avoided.     

Differences between Four Skinfold Calipers in the Assessment of Adipose Tissue in Young Adult Healthy Population

Background: The aim of this study was to analyze the validity of four different skinfold calipers, as well as to establish the differences between them in a healthy young adult population. Methods: The present study followed a cross-sectional design, including 138 participants, with 69 males (21.46 ± 2.52 years) and 69 females (22.19 ± 2.85 years). The measurement protocol included basic measurements of body mass and stretch stature and eight skinfolds with a Harpenden, Holtain, Slim Guide, and Lipowise. The ∑6 and ∑8 skinfolds and fat mass were calculated. The order in which the skinfold calipers were used was randomized. Results: No significant differences were found in either the Σ6 and Σ8 skinfolds or masses and fat percentages calculated with the skinfolds obtained with the different calipers (p > 0.05), and the inclusion of the covariates of sex, BMI, and hydration status of the participants showed no effect on the differences. The Bland–Altman test showed significant differences between the calipers (p < 0.001). Conclusion: It has been observed that the analyzed calipers have shown validity for the assessment of adiposity-related variables in a male and female sample of non-overweight, young healthy adults, but they are not interchangeable with each other when the assessment is meant to be compared over time or with other samples.     

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.