A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia-reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery.

Reparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemia-reperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann-Whitney U- and Fisher's exact tests. Thirty- and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45-57 versus 58%, IQR = 53-66, P = 0·035], end (71%, IQR = 67-76 versus 79%, IQR = 71-83, P = 0·023) and 1 h after CPB (73%, IQR = 71-75 versus 77%, IQR = 72-80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027-3080 versus 3200 ml, IQR = 2928-3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023-4288 versus 4200 ml, IQR = 2313-8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 µg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood.

Management of microanastomosis in patients affected by vessel diseases.

OBJECTIVE: In the last 10 years with the advances in microsurgery of techniques and materials the indications for free tissue transfer have considerably been increased. But, there are still some limitations and drawbacks. Among risk factors associated with flap failure, atherosclerosis can affect both the flap and the recipient vessels of free microvascular tissue transfers. The purpose of this paper is to discuss about the pathogenesis of Monckeberg's sclerosis, and the topics that must be taken into consideration when performing microsurgery in these patients. METHODS: PubMed database was searched using Mesh. The following terms was added to the search builder: Monckeberg's sclerosis, free flap. The Boolean operator "AND" was selected. All the selectable Mesh headings for "Monckeberg's sclerosis" and "free flap" were included. RESULTS: Almost all the literature works about microsurgery in Monckeberg's sclerosis patient show the importance of an accurate preoperative and postoperative evaluation and of a proper surgical technique. CONCLUSIONS: When adequate preoperative evaluation, surgical technique and postoperative monitoring are performed, even severe atherosclerosis should not be considered an absolute contraindication for microvascular surgery.

Reduced expression of CDKN2a/P16INK4a in mycosis fungoides.

Alterations in the CDKN2a gene have been demonstrated in a wide range of human tumors including hematopoietic malignancies. To verify whether altered CDKN2a expression is involved in the pathogenesis of mycosis fungoides (MF), we examined mRNA expression in 20 patients with MF by RT-PCR and dot blot hybridization. CDKN2a mRNA expression was undetectable in 5 of the 20 patients (25%), intermediate in 13 (65%) and high in 2 (10%). Immunohistochemical studies, which were performed in ten patients, revealed that in the four patients showing no mRNA, p16INK4a was expressed in <1% of neoplastic lymphocytes whereas in the four patients with an intermediate mRNA level, specific nuclear staining was present in 1-25% of tumor cells. In the two patients with high levels of CDKN2a mRNA, >25% of neoplastic lymphocytes stained positively. No direct correlation between clinicopathological and molecular findings was evident in our patients. DNA mutational analysis revealed no alterations in a total of six patients examined. Our results indicate that the lack of CDKN2a expression, as found in 25% of the patients, may have a pathogenetic role in MF even though the absence of CDKN2a mRNA was not associated with point mutations or minor gene deletions.

Induction of functional empty class I major histocompatibility complex glycoproteins by photoactivated 8-methoxypsoralen.

CD8+ cytotoxic T lymphocytes (CTLs) bind to and selectively lyse tumor cells via T-cell receptor recognition of distinctive peptide antigens presented in the context of surface major histocompatibility complex class I (MHC class I) glycoproteins. Several human and experimental animal tumors express distinctive MHC class I-associated peptides, which can be selectively targeted by specific CD8+ CTLs. Malignant cells expressing low quantities of these peptides are poor inducers of CTL responses. Therefore, we have developed a method of externally loading increased amounts of antigenic peptides onto MHC class I molecules. In order to induce "empty" fillable MHC class I molecules capable of binding antigenic peptides, we exposed transformed murine T cells (RMA) to low dose (3 joules/cm2) ultraviolet A energy and 8-methoxypsoralen (100 ng per ml). Presence of "empty" class I molecules was ascertained by "meltdown" or loss of the thermodynamically unstable cold-induced "empty" molecules as identified by cytofluorography at 37 degrees C. Retained function of "empty" molecules was determined by their stabilization through addition of peptides of the correct size and sequence motif, prior to exposure to physiologic temperature.

Nutritional state and exercise tolerance in patients with COPD.

We hypothesized that in patients with COPD, poor nutritional status adversely influences exercise tolerance by limiting aerobic capacity of exercising muscles. In 28 patients with stable COPD, we correlated nutritional status with gas exchange indexes obtained during maximal incremental cycle ergometer exercise and with respiratory function parameters. On the basis of percent of ideal body weight (%IBW), patients were divided into three groups (GP): GP1 (n = 8, %IBW < 90); GP2 (n = 13, %IBW > or = 90 < 110); and GP3 (n = 7, %IBW > or = 110). When compared with normally nourished individuals (GPs 2 and 3), malnourished GP1 patients showed greater reduction in maximal workload and in peak O2 uptake (VO2 peak), with earlier onset of metabolic acidosis (anaerobic threshold [AT]); in addition, indexes reflecting O2 cost of ventilation were higher in GP1. Nutritional status could be correlated with exercise tolerance (VO2 peak, r = 0.82, p < 0.0001), with onset of metabolic acidosis (AT, r = 0.69, p < 0.0001) and with dead space/tidal volume ratio (VD/VT, r = -0.59, p < 0.001). Body weight was inversely correlated with indexes that are likely to reflect the increase in O2 cost of ventilation. We conclude that in patients with stable COPD, (1) malnutrition significantly affects muscle aerobic capacity and exercise tolerance, and (2) high wasted ventilation and O2 cost of ventilation may be responsible for the weight loss.

Endocrine changes and clinical outcome after laparoscopic ovarian resection in women with polycystic ovaries.

Ovarian laparoscopic resection was applied to 23 sterile patients affected with polycystic ovarian disease (PCOD) resistant to different pharmacological treatments, in order to induce ovulation. After resection, 56% of the patients had spontaneous ovulatory cycles and 13 pregnancies arose. Ten of the pregnancies were spontaneous and three followed treatment with clomiphene. Hormone changes were assessed in 15 patients, including five with spontaneous menstruation but without ovulation and five with persistent amenorrhoea for 3 months after resection. A significant decrease in both androstenedione and testosterone levels occurred in all patients. These decreases were not related to the clinical results of resection. Luteinizing hormone (LH) did not vary greatly in any group after resection. Mean values and mean pulsatility of follicle stimulating hormone (FSH) increased significantly only in pregnant patients or those with spontaneous ovulatory cycles. The results of gonadotrophin-releasing hormone (GnRH) assays did not change after resection. The mechanisms involved in the resumption of cyclic function of the hypophyseal-ovarian axis after resection are discussed briefly.

Incidence of acid-base and electrolyte disturbances in a general hospital: a study of 110 consecutive admissions.

To establish the overall frequency distribution and combination of acid-base and electrolyte disturbances as they occur in a general population requiring hospital care, we studied arterial blood gases and plasma electrolytes (sodium, potassium and chloride) in 110 consecutive patients (age = 68 +/- 8 SE; 64 M, 46 F) at the time of admission to a general medical ward. Disturbances were defined on the basis of the standard pH/pCO2 plot and the normal (mean +/- 2 SD) electrolyte range for our laboratory. Sixty-two patients (56%) showed a disturbance in acid base equilibrium: acidosis: respiratory 16, metabolic 6; alkalosis: respiratory 26, metabolic 10; in 4/62 the acid base disturbance was mixed. In 47 of the 62 patients, the acid base imbalance were associated with electrolyte derangements (low PNa+, 12; high PNa+, 1; low PK+, 10; high pK+, 7; increased anion gap, 17). Electrolyte disturbances with a normal acid base status were detected in only 2 patients. Of significance, in 7 of the 58 individuals considered to have a "pure" acid base disturbance on the basis of the pH/pCO2 plot (5 respiratory alkalosis; 1 respiratory acidosis; 1 metabolic alkalosis), a widened anion gap revealed that the acid-base change was mixed, i.e. there was a concomitant component of metabolic acidosis. Thus, the total number of mixed acid base equilibrium disorders were eleven. This study emphasizes the frequent incidence of acid base and electrolyte disorders, very often in combination, among unselected adult patients admitted to a general medical ward. In addition it reinforces that a high prevalence of hidden cases of mixed acid base disturbances can be recognized by concomitant analysis of acid base and electrolyte parameters, including anion gap calculation.

Jaw muscle silent periods before and after rapid palatal expansion.

1. The electromyographic silent period was observed in jaw-closing muscles during a maximal clench following a tap to the mandibular symphysis in eight subjects before and after rapid palatal expansion. 2. No differences in mean silent period duration were observed among the three jaw-closing muscles examined. 3. A large (r = 0.96) and statistically significant (p less than 0.01) correlation coefficient between two sets of silent period durations at one session indicates that these measurements are repeatable and reliable. 4. The mean silent period duration for the eight patients with malocclusions was 33.5 msec. prior to rapid palatal expansion and 51.2 msec. after the completion of palatal expansion. The difference was statistically significant (p less than 0.01) and represents a 61 percent increase. 5. Patients with symptoms of TMJ dysfunction are not the only group showing a prolonged silent period duration.