Patterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsis.

Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

Patterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsis

Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

Typical and atypical enteropathogenic Escherichia coli bacterial translocation associated with tissue hypoperfusion in rats.

Although enteropathogenic Escherichia coli (EPEC) are well-recognized diarrheal agents, their ability to translocate and cause extraintestinal alterations is not known. We investigated whether a typical EPEC (tEPEC) and an atypical EPEC (aEPEC) strain translocate and cause microcirculation injury under conditions of intestinal bacterial overgrowth. Bacterial translocation (BT) was induced in female Wistar-EPM rats (200-250 g) by oroduodenal catheterization and inoculation of 10 mL 10(10) colony forming unit (CFU)/mL, with the bacteria being confined between the duodenum and ileum with ligatures. After 2 h, mesenteric lymph nodes (MLN), liver and spleen were cultured for translocated bacteria and BT-related microcirculation changes were monitored in mesenteric and abdominal organs by intravital microscopy and laser Doppler flow, respectively. tEPEC (N = 11) and aEPEC (N = 11) were recovered from MLN (100%), spleen (36.4 and 45.5%), and liver (45.5 and 72.7%) of the animals, respectively. Recovery of the positive control E. coli R-6 (N = 6) was 100% for all compartments. Bacteria were not recovered from extraintestinal sites of controls inoculated with non-pathogenic E. coli strains HB101 (N = 6) and HS (N = 10), or saline. Mesenteric microcirculation injuries were detected with both EPEC strains, but only aEPEC was similar to E. coli R-6 with regard to systemic tissue hypoperfusion. In conclusion, overgrowth of certain aEPEC strains may lead to BT and impairment of the microcirculation in systemic organs.

Typical and atypical enteropathogenic Escherichia coli bacterial translocation associated with tissue hypoperfusion in rats

Although enteropathogenic Escherichia coli (EPEC) are well-recognized diarrheal agents, their ability to translocate and cause extraintestinal alterations is not known. We investigated whether a typical EPEC (tEPEC) and an atypical EPEC (aEPEC) strain translocate and cause microcirculation injury under conditions of intestinal bacterial overgrowth. Bacterial translocation (BT) was induced in female Wistar-EPM rats (200-250 g) by oroduodenal catheterization and inoculation of 10 mL 10(10) colony forming unit (CFU)/mL, with the bacteria being confined between the duodenum and ileum with ligatures. After 2 h, mesenteric lymph nodes (MLN), liver and spleen were cultured for translocated bacteria and BT-related microcirculation changes were monitored in mesenteric and abdominal organs by intravital microscopy and laser Doppler flow, respectively. tEPEC (N = 11) and aEPEC (N = 11) were recovered from MLN (100 percent), spleen (36.4 and 45.5 percent), and liver (45.5 and 72.7 percent) of the animals, respectively. Recovery of the positive control E. coli R-6 (N = 6) was 100 percent for all compartments. Bacteria were not recovered from extraintestinal sites of controls inoculated with non-pathogenic E. coli strains HB101 (N = 6) and HS (N = 10), or saline. Mesenteric microcirculation injuries were detected with both EPEC strains, but only aEPEC was similar to E. coli R-6 with regard to systemic tissue hypoperfusion. In conclusion, overgrowth of certain aEPEC strains may lead to BT and impairment of the microcirculation in systemic organs.

Bacterial translocation, microcirculation injury and sepsis.

Sepsis is the result from a complex bacterial-host interaction, which is an often-fatal response when host protective molecular mechanisms designed to fight invading bacteria surpass the beneficial intensity to the point of causing injury to the host. Increasing evidences have implicated the bacterial translocation (BT) as the main source for the induction of sepsis, although the beneficial effect of BT process has been related to the development of the intestinal immune response by physiological interaction between bacteria and host. In this article, we examined evolving concepts concerning to BT and discussed about its potential role in the promotion of microcirculation injury, moreover, its possible participation in the sepsis induction. According to our data obtained from in-vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic determinants seem to be major predisposing factors for the induction of BT. Besides, translocation of luminal bacteria through the lymphatic via elicits the activation of the GALT inflammatory response contributing to microcirculation injuries, and the haematological via of BT was responsible to the systemic bacterial spread. On other hand, the combination of BT process to the pre-existing host systemic infection played a crucial role in the worsening of the clinical outcome. In our understanding, studies concerning to intestinal immune response and the pathophysiology of bacterial-host interaction, under normal and disease conditions, seems to be the key elements to the development of therapeutic approaches towards sepsis.

Reparation of a severe case of aplasia cutis congenita with engineered skin.

Aplasia cutis congenita (ACC) is an uncommon congenital malformation. It is characterized by defects of the skin that occur most frequently on the scalp along the midline, but can also be localized on the trunk, face and limbs, usually with a symmetrical distribution. When it is localized in the skull it can extend to the dura mater, leaving only the thin pia mater to protect the brain. The most common complications related to this disorder are infection, hemorrhage, and, in defects localized on the vertex, meningitis and bleeding from the sagittal sinus can occur with dramatic consequences. In those cases some authors suggest the use of local flaps even if this implies a surgical procedure. In this case a 2.540-kg baby was delivered at 40 weeks of gestation by eutocic delivery, and good adaptation to extrauterine life. At birth the baby showed a large cutaneous and osseous defect at the vertex measuring 68 cm(2), equal to almost one third of the calvarial surface, and extended to the dura mater through which it was possible to see the sagittal sinus and the brain surface with its vessels. Skull X-rays showed loss of normal radioopacity of the cranial vault with lack of ossification especially at the parietal level. In our patient we therefore decided to use a composite graft of cultured autologous fibroblasts and keratinocytes to provide coverage, avoiding any surgical procedure and patient morbidity. This technique consists first in an autograft of cultured fibroblasts which has proved to promote the production of type IV collagen, fibronectin and laminin whereby creating an ideal bed for the taking of the graft of cultured keratinocytes, to be put in place a week later. The use of a composite graft with both the derma-like and epithelial components has been also suggested to diminish scarring. Two months after the last graft area was completely closed.

A case of non-immune hydrops fetalis with congenital cystic adenomatoid malformation of the left lung in a twin.

Hydrops fetalis is a rare condition that occurs in one out of every 1,400-4,000 pregnancies. There are two types, immune and non-immune. It can be caused by a maternal-fetal incompatibility due to the Rh factor or, more rarely, the Kell factor or due to other antigens to red corpuscles. Non-immune types of hydrops have a complex multiform pathogenesis and in 50% of the cases they are of idiopathic nature. The causes that could determine non-immune hydrops are manifold and in 50% of the cases they are of an idiopathic nature. Independently of the clinical condition, the presented case could be classified in those forms of pathogenesis in which there is the presence of a congenital cystic adenomatoid malformation (CAM), not encountered in the fetal ultrasound performed at the sixteenth week of pregnancy. The particularity of our case is due to the association of the fetal hydrops of the CAM type in only one of the two twins. The presented case is classified in those forms of hydrops that are expressed with a clinical trend towards a worse prognosis, characterized by the intrauterine death of the fetus or the birth of a hydropic fetus that does not survive because of respiratory insufficiency and cardiocirculatory collapse.

Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues.

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

[Echography of the hip in premature infants]. / Ecografia dell'anca nel prematuro.

The authors report the data relative to 50 preterm infants with gestational age less than or equal to 34 weeks. The newborns were studied sequentially with clinical and US examination from February 28, 1989 to March 23, 1990 in order to exclude hip dysplasia or dislocation. US examination was carried out according to Graf's technique. All the newborns had another clinical examination at one year of age in order to evaluate their normal walking. Risk factors had poor significance in the studied group of infants.

[Surfactant and ambroxol in the therapy of idiopathic respiratory syndrome in newborn infants]. / Surfactant e ambroxol nella terapia della sindrome respiratoria idiopatica del neonato.

The Authors have carried out a study on 30 newborns, affected by idiopathic respiratory distress syndrome (IRDS), divided into 3 statistically comparable groups, treated, in addition to mechanical ventilation, respectively with Tokio-Akita (TA) surfactant, placebo (both by endotracheal administration) and ambroxol given by intravenous infusion. The clinical evolution of the three groups was studied, above all as related to mortality, ventilation length, oxygen need, immediate and successive pulmonary complications and cerebral haemorrhage. Mortality was lower in the group treated with ambroxol, while the ventilation length, the average insufflation pressure and the oxygen need were lower in the group treated with surfactant, compared with the other two groups. Pulmonary complications were present only in the group treated with placebo and ambroxol, whereas cerebral haemorrhage rate is higher in the group treated with surfactant. On the basis of the results achieved, some important observations are suggested and possible aetiological therapies of IRDS are formulated.

[Pulmonary edema. A rare complication of the percutaneous insertion of silastic central venous catheters]. / Edema polmonare. Una rara complicanza del catetere siliconato venoso centrale ad inserzione percutanea.

Seven newborn infants (birth weight 920 to 1,900 g) who developed pulmonary oedema as a complication of the use of percutaneous silastic central venous catheters are described. Clinical symptoms occurred three to forty days after catheter placement. In each case, radiographic detection, performed by the injection of radiopaque dye, localized the tip of the catheter in the pulmonary artery or in its collateral branches. Clinical symptoms decreased after catheter replacement in the right atrium. The casistic examination allows the Authors to suggest some aetiopathogenetic hypothesis.

[Substitutive therapy with surfactants in premature infants with respiratory distress syndrome]. / Terapia sostitutiva con surfattante in prematuri affetti da respiratory distress syndrome.

The main pathogenetic moment of the respiratory distress syndrome (RDS) is recognized to be the lack of alveolar surfactant. Many attempts of substitutive therapy with several kinds of surfactants have been tried (artificial, synthetic, from amniotic fluid, exosurf). After the considerable results obtained in animals, the use of substitutive surfactant proved to be useful also in human newborns with RDS. The authors report the personal data relative to the TA-surfactant (artificial surfactant made of phospholipids + DPPC + protein substances extracted from bovine lung). They analyse first results and, on this ground, they put forward some assumptions in order to obtain a more rational and efficient use.

[Percutaneous silicone catheters in the newborn infant]. / Cathéters percutanés siliconés chez le nouveau-né.

246 percutaneous insertions of silastic venous catheters were performed in 189 newborn infants. This technique makes perfusion in newborn easier and safer, with less complication risks and less work for nurses. Furthermore silastic venous catheters insure a better observation of neonatological care methods. As a consequence it improves the vital prognosis and the quality of newborn survival in the newborn intensive care unit.