Evolution of a percutaneous fetoscopic access system for single-port tracheal occlusion

Background/Purpose: Prenatal tracheal occlusion currently is being assessed as a treatment modality for congenital diaphragmatic hernia (CDH). The development of a totally percutaneous fetoscopic access system would help avoid the need for maternal laparotomy and reduce the morbidity rate of fetal surgical procedures for the mother. Laparoscopic radial expansion sheaths and Seldinger technique[ndash ]based vascular catheters both have been advocated as means of achieving amniotic cavity access. The authors have investigated these 2 systems in an attempt to develop a reliable method for achieving safe percutaneous fetoscopic access and present the first successful attempt to deploy an intratracheal balloon using an entirely percutaneous approach through a single port in an ovine model. Methods: A number of prototype systems were evaluated sequentially over a 3-year period in an ovine model: (1) the radially expanding InnerDyne step port system, (2) a new rigid cannula with a bulbous/sharp end preloaded onto the radially expanding InnerDyne port, (3) a conical removable addition to the rigid cannula in 2, (4) a modified bulbous/sharp ended cannula incorporating a circumferential protective insert, (5) a rigid split sheath with the radially expanding port placed through the lumen of the split sheath, (6) a flexible introducer and dilator with the split sheath (used in the Seldinger placement of central lines), and (7) a 2-needle approach using a superelastic shape-memory alloy Nickel-Titanium wire with the flexible dilator and sheath, incorporating a side perfusion port. For balloon tracheal occlusion, live anaesthetized time-mated pregnant ewes were used at 110 days' gestation. Tracheobronchoscopy was achieved using a 3-mm 0[deg ] telescope, and the cutaneotracheal tract was secured by a 3.3-mm sheath incorporating a side-perfusion port. The rigid telescope was replaced by a flexible choledochoscope preloaded with a silicone balloon. The balloon was deployed 2 cm above the carina proximal to the right upper lobe bronchus. Results: The many problems encountered in the evolution of the preferred system related mainly to separation and tenting of the chorioamniotic membranes in the ovine uterus and inconsistent access to the fetal parts of interest. Each resulted in significant modifications to our approach. Furthermore, the use of rigid access devices commonly caused fetal injury. Successful access to the intrauterine cavity and cannulation of the trachea was achieved consistently with minimal trauma, irrespective of fetal position by method 7. Multiple port placement allowed visualization of the entry of all components of the system confirming minimal chorioamniotic membrane separation and tenting. Single port tracheal occlusion was undertaken first on 6 cadavers before being performed successfully on 3 live anaesthetized ewes. Fetoscopic access and cannulation of the trachea was achieved consistently in all live animals irrespective of fetal position. Conclusions: This modified Seldinger technique using the unique properties of the memory-shaped alloy wire for initial uterine access offers a safe method for the percutaneous placement of fetoscopic ports in the ovine model for prenatal intervention. Successful placement of a tracheal balloon entirely through a single percutaneously placed port represents a further advance in prenatal therapy for CDH. J Pediatr Surg 38:45-50.     

Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin

Inhibition of wound contraction by topical anti microbial agents has been described. The purpose of this study was to further investigate that phenomenon and to explore the effect that other agents such as Aloe vera might have on this process.

Full-thickness excised wounds were created on the dorsum of Sprague-Dawley rats under anaesthesia. The wounds were treated with topical agents three times daily for fourteen days, then observed until healed. Groups were: saline control, placebo (aqueous cream) control, silver sulphadiazine (SSD) cream 1%, SSD 0.5%, SSD 1% with Aloe vera, SSD 1% with nystatin, nystatin. Wound surface areas were measured each three days. Time to 50% and 90% healing was compared using ANOVA.

Wound half-life and healing times were shortest in the SSD/Aloe vera and nystatin groups (P<0.05) and longest in the 1% SSD and saline control groups. The placebo group (aqueous cream) healed in a significantly shorter time (P<0.05) than the control (saline) group.

Wound contraction was delayed by saline and SSD. Nystatin and Aloe vera, when added to SSD, reversed that effect.

These data suggest that a dry wound (saline) heals slowly. Infection control without delay of wound healing is most appealing and clinical trials are planned.     

Raccoon poxvirus as a mucosal vaccine vector for domestic cats

In the present study, we evaluated both the immunogenicity and safety of recombinant raccoon poxvirus (RCN) as a mucosal vaccine vector for domestic cats. RCN is an orthopoxvirus that was isolated from healthy raccoons and has been used experimentally as a vaccine vector for rabies and other antigens in a variety of species, including raccoons, skunks, foxes, bobcats, rabbits, domestic cats, piglets, sheep and non-human primates. We evaluated the antibody response induced by a recombinant RCN vaccine expressing the rabies-G glycoprotein (RCN/rabies-G) administered to cats by the oral (PO), intranasal (IN), conjunctival (CO) or intranasal/conjunctival (IN/CO) route (dose: 10 plaque forming units or PFU). The IN route, either alone or combined with the CO route, induced the highest rabies virus neutralizing antibody (RVNA) titers. The RVNA titers remained high when measured at six months post-vaccination, demonstrating that the recombinant vaccine administered via these routes is very efficient at inducing long-lasting immunity. A dose-response was observed following IN vaccination in cats. Doses of 10 PFU induced strong antibody responses in 4 of 5 animals [geometric mean titer: 3.2 (log)]. None of the animals vaccinated with 10 PFU developed detectable RVNA titers. In this study, RCN/rabies-G viral shedding was below detectable levels. Nasal, oral and fecal swabs collected from these cats were negative for RCN by both virus isolation and by nested-PCR. In addition, no horizontal transmission of the virus could be detected. Gang-housed sentinel animals for each group did not develop detectable anti-RVNA or -RCN antibodies. To study tissue tropism of recombinant raccoon poxvirus vaccines, a RCN that can express the lacZ gene (RCN/lacZ) was constructed. Expression of beta-galactosidase (beta-gal) was validated in vitro and in mice in vivo. Cats were vaccinated IN with 10 PFU of RCN/lacZ. No histopathological lesions were detected in any of the tissues collected from these cats at 1, 4, 7 and 15 days post-vaccination. In addition, no virus or beta-gal expression was detected in any of these tissues. Controls demonstrated that virus could be reisolated from nasal swabs immediately after administration of 10 PFU to cats. These results suggest that recombinant RCN vaccines undergo limited replication after intranasal administration in cats that is sufficient to elicit strong, long-lasting systemic antibody responses.     

ER-alpha variants and the cardiovascular effects of hormone replacement therapy

There is an accumulating body of evidence linking estrogen receptor-alpha (ER-alpha) gene polymorphisms with variation in cardiovascular risk factors or disease. The ER-alpha IVS1-397 T/C (PvuII), IVS1-351 A/C (XbaI) and the promoter region TA repeat polymorphisms have received the most attention. If ER-alpha genetic variants identify women at high risk for cardiovascular events, this information could be used to improve clinical decisions regarding the use of hormone replacement therapy (HRT). More detailed haplotype and genome-wide studies of many of the major HRT clinical trial cohorts are currently underway and these efforts promise to clarify many outstanding issues concerning estrogen action and cardiovascular disease.     

Pharmacotherapy of first-episode psychosis

Early intervention in psychosis has attracted more attention in the last few years. The treatment of this phase of the disorders requires a specific and adapted approach. The issue of engaging the patient is so critical that it influences not only the choice of medication, but also the context and the way in which it is administered. In the case of a first admission, patients should be observed for 24-48 h without any antipsychotic treatment, in order to clarify the diagnosis and exclude the possibility that symptoms are caused by acute intoxication with illicit substances, for example. The diagnosis is often difficult and unstable. A dimensional, rather than a categorical approach, is usually more likely to be adopted. In recent years, atypical antipsychotics have become the most frequently used first-line treatment. They are less likely to cause secondary negative symptoms, cognitive impairments and dysphoria. They also appear to influence the course of depression and hostility/aggression better than conventional neuroleptics, have possibly mood-stabilising properties and, subjectively, are often better accepted by patients. On the risk side, prevalence of acute extrapyramidal side effects and possibly tardive dyskinesia are lower, compared to the older neuroleptics. Although, the risk for short-term weight gain, cardiovascular, and especially hyperglycaemic complications are somewhat higher for some of these antipsychotics. Finally, the dose should be adapted as it has been shown that patients presenting a first psychotic episode respond to a lower dose of antipsychotic. This article focuses on the pharmacotherapy of first-episode psychosis, on the basis of a computerised and a manual search for articles dealing with antipsychotic treatment of these patients. Findings are discussed and combined in clinical guidelines for first-episode affective and non-affective psychosis, for patients with incomplete recovery or treatment resistance, for cases of emergency and for side effects associated with antipsychotic treatment.     

Behavioral effects of neuropeptide Y in F344 rat substrains with a reduced dipeptidyl-peptidase IV activity

Dipeptidyl-peptidase IV (DPPIV/CD26) is involved in several physiological functions by cleavage of dipeptides with a Xaa-Pro or Xaa-Ala sequence of regulatory peptides such as neuropeptide Y (NPY). Cleavage of NPY by DPPIV results in NPY(3-36), which lacks affinity for the Y(1) but not for other NPY receptor subtypes. Among other effects, the NPY Y(1) receptor mediates anxiolytic-like effects of NPY. In previous studies with F344 rat substrains lacking endogenous DPPIV-like activity we found a reduced behavioral stress response, which might be due to a differential degradation of NPY. Here we tested this hypothesis and administered intracerebroventricularly two different doses of NPY (0.0, 0.2, 1.0 nmol) in mutant and wildtype-like F344 substrains. NPY dose-dependently stimulated food intake and feeding motivation, decreased motor activity in the plus maze and social interaction test, and exerted anxiolytic-like effects. More important for the present hypothesis, NPY administration was found to be more potent in the DPPIV-negative substrains in exerting anxiolytic-like effects (increased social interaction time in the social interaction test) and sedative-like effects (decreased motor activity in the elevated plus maze). These data demonstrate for the first time a differential potency of NPY in DPPIV-deficient rats and suggest a changed receptor-specificity of NPY, which may result from a differential degradation of NPY in this genetic model of DPPIV deficiency. Overall, these results provide direct evidence that NPY-mediated effects in the central nervous system are modulated by DPPIV-like enzymatic activity.     

Intervention effects in observational survival studies with an application in total hip replacements

Time to revision is a common and clinically relevant endpoint for studies of patients with total hip replacement. Because failures occur rarely within the first years after replacement, new surgical techniques and materials are often implemented without evidence of their effectiveness from randomized trials. Observational data may be available but this relies on the use of historical controls which has been heavily criticized. Instead the use of changepoint methods has been suggested to detect changes caused by successfully implemented interventions. In the setting of a proportional hazards model we develop a semi-parametric changepoint method to detect changes in baseline hazard. The procedure is motivated by and applied to a clinical study in patients with total hip replacements, where the effect of a new cement type is of interest. Power properties of the proposed method are investigated.