Laparoscopic versus open appendectomy in the management of acute appendicitis in children: a multicenter retrospective study.

AIM: Acute appendicitis is one of the most common indications for emergency surgery in children. Open appendectomy (OA) has been the gold standard treatment for over 100 years. In the last three decades, the introduction of minimally invasive techniques, such as laparoscopic appendectomy (LA) and transumbilical laparoscopically assisted appendectomy (TULAA), has changed the approach to the disease. However, there is still no agreement with benefits of these new therapeutic options, especially in children. The aim of this retrospective study is comparing the outcomes of OA, LA and TULAA in the paediatric patient. METHODS: Children suffering from acute appendicitis were treated with LA or TULAA in the Department of Paediatric Surgery and with OA in the Department of General Surgery. Data were abstracted from database of both centers' archives. Operator, operating time, length of hospitalization (LOH), intra- and postoperative complications and histological finding were analyzed. RESULTS: We recruited 196 patients: 46 treated with LA, 62 with TULAA and 88 with OA. Operative time was significantly shorter in OA. The three techniques had the same incidence of intraoperative and postoperative complications. The incidence of wound infection was higher with the TULAA approach. LOH was significantly shorter in the TULAA group. There was no correlation between LOH and histological finding. CONCLUSION: We demonstrated that LA, TULAA and OA are similar in most respects and are equally safe modalities in paediatric patients. Further randomized controlled studies are necessary.

Advance treatment directive: a tool for dialogue or self-protection in the physician-patient relation?

The authors intend to assess the efficacy of the advance treatment directive as a tool for involving patients into the decision-making process and the actual implementation of the physician-patient communication. It seems particularly appropriate to distinguish between "generic" advance directive, happening outside of the physician-patient relation, and documents drafted with the assistance of care providers, in the context of such an information and communication process. That is, in order to guarantee the awareness of patients and the pertinence of the disclosed indication to the current situation with reference to the subject-matter of advance treatment directive. In addition, considering the different ways for the will of a patient to be conveyed--written statements, unexpressed will reported by witnesses, expressed will in an intelligible way by patients with severe verbal communication deficit--it is deemed important to identify the formal requirements for the validity of the above expressions of will. From an ethical standpoint, if we transcend a merely contract-centred and defensive vision of the physician/patient relation, the positive meaning of autonomy lays in its effective enforcement in the decision-making and care processes, with regard to the defined circumstances and the specific objects it refers to. Physician/patient communication means, for the purposes of this discussion, a preferential tool to balance the substantially asymmetrical relation between a physician and a patient: the process is based on a path of mutual recognition where the formal protection of each other's scopes of competency and right to self-determination stand for an essential requisite, though only preliminarily, to the actual accomplishment of consent in its cognitive and practical features.

Selective outgrowth and differential tropism of amacrine and photoreceptor axons to cell targets during early development in vitro.

The axonal guidance and outgrowth in retinal neurons were investigated in cultures of pure retinal neurons (control) or in cocultures with heterologous BC3H-1 cells. Under control conditions, only about 10% of retinal neurons developed axons; coculturing with BC3H-1 cells induced early axonal outgrowth and guidance to BC3H-1 cells in most amacrine neurons. Both mechanisms were dependent on laminin and neural cell-adhesion molecules (N-CAMs) released by BC3H-1 cells, because they were prevented by antibodies directed against these molecules. The protein kinase C (PKC) inhibitor, staurosporine, reduced the effect of laminin on amacrine axonal outgrowth, suggesting that this effect was mediated by PKC. The occurrence of structures resembling synaptic boutons and the expression of synaptophysin at the amacrine axon ends of heterologous connections suggested that amacrine axons establish true synaptic contacts rather than simply overlapping with the BC3H-1 cells. In contrast to the heterologous contacts with BC3H-1 cells, the amacrine-amacrine axonal contacts observed in the cocultures were independent of laminin and N-CAM. Axonal outgrowth occurred in about 10% of the photoreceptors and was not affected by BC3H-1 cells or by substratum pretreatment with laminin or N-CAM. These results show that different mechanisms affect axonal outgrowth and guidance in amacrine and photoreceptor neurons in vitro, and they suggest that similar mechanisms could contribute to the development of the scaffold of axon pathways in the retina in vivo.

Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer.

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T. In the present study we adopted a treatment schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60 mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T (30 mg/day). We obtained a 13% response rate with a median duration of response of 8 months (range 4-16 m). All the responses occurred in pts whose disease progressed after an initial response to T. Stabilisation of disease was observed in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN-beta in the treatment of breast cancer remains investigational and the optimal scheduling still undetermined.

Synthesis and inhibitory activities on platelet aggregation of some flavonoid analogues.

A series of 26 benzodioxan and benzodioxol derivatives of flavone have been prepared. The activity of the compounds on washed human platelet aggregation induced by adenosine diphosphate (ADP, 5 mumol/l), collagen (10 micrograms/ml) and calcimycin (20 mumol/l) was evaluated. The alkoxycarbonyl side chain derivatives inhibited all three types of aggregation inducers. Among the tested compounds Ia is the most potent inhibitor of collagen-induced aggregation but possesses a weak activity against the other two used inducers. The esters IIIb and in particular, IIIc are active against all the three used inducers. These results suggest that ethoxycarbonyl group is a potent substituent to provide the antiplatelet action in this series of flavonoids.

Thrombin induces S-D-lactoylglutathione accumulation by enhancing platelet glycolytic pathway.

1. Thrombin addition to human platelets stimulates L(+)lactate formation and S-D-lactoylglutathione (SDL) accumulation. 2. Monoiodoacetamide decreases lactate formation and potentiates SDL accumulation through a significant increase of dihydroxyacetone phosphate and fructose1,6bisphosphate intracellular levels both in resting and in activated platelets. 3. A similar effect is produced by exogenous methylglyoxal on L(+)lactate formation and SDL accumulation. 4. Resting platelets completely transform (1 hr at 37 degrees C) the ketoaldehyde into D(-)lactate: 5. When platelets are incubated in the presence of thrombin only 60% of the ketoaldehyde is found as D(-)lactate and the accumulated S-D-lactoylglutathione represents about the 0.7% of the initial substrate. 6. During platelet stimulation with thrombin the hemithioacetal adduct, formed as a by-product of glycolytic pathway, can be rapidly removed for important steps of cellular activation.

S-D-lactoylglutathione accumulation in activated human platelets.

1. S-D-Lactoylglutathione accumulates in human platelets activated by agonists. Among the tested inducers thrombin is the most active. 2. The effect is dose and time-dependent. S-D-Lactoylglutathione, corresponding to depleted pool of reduced glutathione, can also be detected in platelets incubated with exogenous methylglyoxal. 3. A further significant increase was observed in platelets stimulated with thrombin in the presence of methylglyoxal. 4. No change in glyoxalase activities upon platelet stimulation with thrombin was shown.

Mode of action of 2-(diethylamino)-7-ethoxychromone on human platelets.

The in vitro effect of 2-(diethylamino)-7-ethoxychromone (RC39XVIII) on human platelet aggregation induced by several agonists and on thromboxane B2 formation, granule release and intracellular cAMP elevation has been studied. The chromosome-derivative exerts a dose-dependent inhibitory effect on aggregation produced by U46619, arachidonic acid, thrombin, collagen and ADP. RC39XVIII inhibits aggregation, TxB2 formation and granule release in parallel. Moreover the drug potentiates cAMP accumulation induced by iloprost and forskolin. The drug also inhibits soluble cAMP phosphodiesterase in a dose-dependent manner. No effect on adenylate cyclase activity measured in platelet membranes was evident.

Antiplatelet effect of 2-(diethylamino)-7-hydroxychromone.

In this study the in vitro influence of 2-(diethylamino)-7-hydroxychromone (RC39II) on platelet aggregating responses, thromboxane A2 (TxA2) production, release reaction and intraplatelet cyclic AMP (cAMP) content has been investigated. The drug exerts a dose-dependent inhibitory effect on aggregating response to arachidonic acid, U46619, thrombin, collagen and calcium ionophore A23187. Inhibiting concentrations of RC39II also prevent platelet release reaction and TxA2 formation. RC39II potentiates platelet cAMP accumulation by Iloprost. Several studies, carried out on soluble cAMP phosphodiesterase (PDE) have shown that the drug inhibits phosphodiesterase in a dose-dependent manner. No effect was shown on adenylate cyclase activity from platelet membranes.

Platelets of patients affected with essential thrombocythemia are abnormal in plasma membrane and adenine nucleotide content.

The adenine nucleotides present in distinct cellular compartments of platelets of 27 patients affected with essential thrombocythemia have been measured. In order to quantify granule-bound nucleotides and adenylic cytoplasmic pool, platelets have been stimulated with thrombin or treated with increasing digitonin concentrations, respectively. Among patients, we have identified two groups: 12 patients (Group 1) had normal platelet level of ATP and ADP both in dense granules as well as in cytoplasmic pool. The other patients (Group 2) had granule ATP and ADP significantly lower and ATP/ADP ratio significantly higher than controls. In these patients an increase in hypoxanthine level, derived from metabolic ATP degradation occurring during stimulation, was observed. In addition, in the latter patients an increased resistance of plasma membrane to digitonin was shown, suggesting that membrane fluidity should be reduced owing to a modified cholesterol/phospholipid ratio.

Protein composition in resting and activated platelets of type I diabetic patients.

Protein composition of platelets of eleven type I diabetic patients and thirteen control subjects were analyzed by SDS polyacrylamide gel electrophoresis. Bands have been scanned and quantified. No significant difference was shown between controls and patients in any of the bands identified in electrophoretic patterns of whole platelet, membrane fraction, resting, activated and aggregated cytoskeleton. Data suggest that alterations observed in platelet function of diabetic patients cannot be connected to the changes in protein composition.

Inhibition of the glycolytic pathway by methylglyoxal in human platelets.

The incubation of human platelets with methylglyoxal and glucose produces a rapid transformation of the ketoaldehyde to D-lactate by the glyoxalase system and a partial reduction in GSH. Glucose utilization is affected at the level of the glycolytic pathway. No effect of the ketoaldehyde on glycogenolysis and glucose oxidation through the hexose monophosphate shunt was demonstrated. Phosphofructokinase, fructose 1,6 diphosphate (F1, 6DP) aldolase, glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate mutase were mostly inhibited by methylglyoxal. A decrease in lactate and pyruvate formation and an accumulation of some glycolytic intermediates (fructose 1,6 diphosphate, dihydroxyacetone phosphate, 3-phosphoglycerate) was observed. Moreover methylglyoxal induced a fall in the metabolic ATP concentration. Since methylglyoxal is an intermediate of the glycolytic bypass system from dihydroxyacetone phosphate to D-lactate, it may be assumed that ketoaldehyde exerts a regulating effect on triose metabolism.

Alkaline extraction and reverse-phase high-performance liquid chromatography of adenine and pyridine nucleotides in human platelets.

The levels of adenine (ATP, ADP, AMP) and pyridine (NAD, NADH) nucleotides in human platelets have been measured by a simple and reproducible method. A rapid alkaline extraction allows a complete recovery of the compounds concerned. The metabolic ATP and ADP in the cytosolic fraction, the amount released upon thrombin stimulation, and the ADP bound to F-actin have also been evaluated. Analysis was performed by reverse-phase, isocratic high-performance liquid chromatography on a 5-microns Lichrosorb RP-18 column with uv detection at 254 nm.

Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide.

The effect of some short-chain fatty acids (SCFA) produced by anaerobic bacteria, namely acetic, propionic, isobutyric, butyric, isovaleric and succinic acids, on production of light and release of lysozyme by human neutrophils exposed to chemotactic peptide fMet-Leu-Phe was investigated. A short period of incubation of neutrophils with SCFA led to marked inhibition of both granulocytic chemiluminescence and degranulation (P less than 0.001). Ultrastructural studies of neutrophils, incubated with concentrations of SCFA inhibiting the chemotactic response, chemiluminescence and release of lysozyme (30 mmol/l), effected alterations in cellular morphology with formation of protrusions of varying shape. The data reported indicate that SCFA might be regarded as important pathogenicity factors. The observed effect on neutrophils could also partially explain the ability of anaerobes to inhibit their own phagocytosis and killing as well as that of the aerobic species present in mixed infections.