In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Response rates,duration of response,and dose response effects in phase I studies of antineoplastics

Summary Over a period of 14 years, 7,960 patients were treated in 228 phase I trials. In these patients, there were 75 complete and 432 partial responses for an overall objective response rate of 6%. Complete responses lasted a median of six months (range 1–18), while partial responses lasted a median of three months (range 1–17). Of note is that no drug has made it to the market which has not had a response in phase I trials. Responses were noted in very diverse histologic types of tumors. Although there were responses at doses which were as low as 3–5% of the recommended dose for phase II trials, the majority of responses did occur at 80–120% of the dose recommended for phase II trials. Although the response rate in phase I trials is indeed low, responses do occur. This response rate information should help the clinician provide facts for the patient considering a phase I trial with new anticancer agents. These findings also emphasize that although phase I trials are characteristically dose-finding studies, if no responses are noted in phase I studies, it is unlikely the drug will be used routinely in the clinic.     

The effect of pre-admission education on domiciliary recovery following laparoscopic cholecystectomy.

OBJECTIVES: The objectives of this randomised controlled study were to determine if pre-admission patient education affects post-operative pain levels, domiciliary self-care capacity and patient recall following a laparoscopic cholecystectomy (LC). Participants were randomised to receive the standard preadmission program (SP) or an individualised, education intervention (El). DESIGN: A pre-operative questionnaire was administered in the pre-admission clinic to determine participants' knowledge of LC and post-operative management. Telephone follow-up and post-operative questionnaire were conducted approximately 14 days post discharge. SETTING: Preadmission clinic of a Sydney, Australia, tertiary referral hospital. SAMPLE: Ninety-three elective LC patients. RESULTS: EI participants experienced lower pain levels and had significantly greater recall of provided information. However, no significant differences were found between the control and intervention groups for domiciliary self-care. CONCLUSION: Pre-admission education intervention helps reduce post-operative pain levels following LC and significantly increases patients' knowledge of self-care and complication management.     

Update on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is one of the most significant chronic illnesses of adults. Comprehensive care of the affected patient requires the medical-surgical nurse to have knowledge of the disease process, collaborative management, and nursing care based on research and current practice guidelines.     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.     

Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice

Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including 5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken to determine whether antagonism of the newly identified 5-HT₇ receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their affinity at the 5-HT₇ receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT₇ receptor and a statistically significant correlation was observed between 5-HT₇ affinity and doses for half-maximal response (ED₅₀) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT_1A, 5-HT_2A or 5-HT_2C receptors. It is also unlikely that interactions between the 5-ht₅ receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this in vivo model have no affinity for the 5-ht₅ receptor. There are similarities between the pharmacology of the 5-HT₇ receptor and that of the 5-HT_1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT_1A affinity was not significant. Furthermore, the 5-HT_1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT_1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT₇ receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with selective 5-HT₇ antagonists. Received: 20 March 1997 / Accepted: 10 August 1997     

Risk Factors for a First Febrile Seizure: A Matched Case-Control Study

Summary We conducted a matched casecontrol study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixtynine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (±6 months), site of routine pediatric care, and date of visit (±weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected preand perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a firstor in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.