A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.     

Adopted Children: Core Issues and Unique Challenges

TOPIC: Psychological impact of adoption and resulting core issues for adopted children. PURPOSE: To raise awareness of the psychological impact of adoption. SOURCES: Published literature and personal observations. CONCLUSIONS: Adoption raises unique issues and challenges for the child and adoptive parents. Resolving the issues of adoption is a lifelong process. Through an awareness of the issues inherent in adoption, nurses and parents can use strategies that will enhance children's self-esteem and decrease their emotional vulnerability. Search terms: Adoption, intervention, loss, self-esteem, strategies     

Treatment Outcomes in Spontaneous Intracranial Hypotension: Do Epidural Blood Patches Stop the Leaks?

Abstract:   Spontaneous intracranial hypotension (SIH) is a postural headache syndrome unrelated to dural puncture. Because of the increasing failure of epidural blood patch (EBP) to relieve headache in SIH, we retrospectively investigated the epidemiological features and treatment outcomes in 55 cases of SIH. The study population was stratified by age and sex; continuous variables were compared for differences by t -tests; categorical variables were compared by Chi-squared analysis or Fisher exact tests. Significant differences were identified by P values of 0.05 or less. The mean age of the study population was 44 ± 12 years with a female to male ratio of 1.3:1.0. Men presented with subdural hematomas ( P  = 0.001) more often than women. Meningeal enhancement on contrast magnetic resonance imaging (MRI) was the most consistent radiographic finding. Radionuclide cisternography (RC) demonstrated thoracolumbar dural leaks in 16 of 22 patients. EBP failures were more common in patients aged 40 and younger than in older patients ( P  = 0.003). Postural headache from SIH was not uniformly responsive to EBP, and had significant comorbidities, especially in men. The management of postural headache in SIH by other techniques to restore brain position and cerebrospinal fluid dynamics should be investigated.     

Reaching mothers of preschool-aged children with a targeted quit smoking intervention

Younger women smoke at disproportionately higher rates than other women and their smoking has a major impact on the health of their young children. To address this problem, a smoking cessation intervention combining minimal advice and assistance from a community health nurse and a tailored self-help guide was developed for low-income women with young children. The program evaluation results reported here were gathered from women using publicly funded pediatric services in four agencies with 32 clinic sites in central and eastern Pennsylvania. Unlike volunteers in formal cessation programs, the women varied widely in their readiness to quit smoking. Follow-up data were obtained from 1,230 female smokers, aged 18 to 39, after receiving brief, individualized smoking cessation advice and encouragement to read the self-help guide. One year later, 12.5 percent reported quitting smoking, and 20.2 percent reported having made a serious quit attempt that lasted at least 7 days. These results suggest that, even among smokers with low socioeconomic status and wide variation in their readiness to quit, minimal intervention programs requiring modest resources can promote cessation.This work was funded under contracts from the Cancer Control Program, Pennsylvania Department of Health (SPC-883141 and SPC-979425). The Quitting Times STOP IT quit smoking protocol was adapted from the Smoking Cessation Project, Maternal and Child Health, Massachusetts Department of Public Health. The authors also wish to express appreciation to the staff of the Division of Population Science, Fox Chase Cancer Center for their contributions to this project and especially those of Chris Jepson, Eunice King, C. Tracy Orleans, and Marjorie Utt.     

Preterm Birth: Implications for Family Stress and Coping

The event of preterm birth represents a significant risk to the equilibrium of the family, often placing the family under significant stress. This paper is intended to assist neonatal nurses in understanding factors related to a family's appraisal of stress and strategies used for coping. Such factors are an important consideration in planning the most effective interventions to support optimal family adaptation to their preterm infant's birth. In identifying the best clinical approaches to supporting a family coping with the event of a preterm birth, nurses need to consider levels of the evidence that supports adoption of clinical intervention strategies. Working to reduce family stress and improve family coping ensures the most optimal home environment for the preterm infant to grow and thrive in after discharge.     

Risk of lung cancer among patients with head and neck cancer

A cohort of 5180 patients with head and neck cancer, who were part of the tumor registry of the Surveillance, Epidemiology, and End Results area of western Washington State, was followed up for as many as 15 years to determine the risk of lung cancer. A sample of 522 patients from this cohort was interviewed to determine smoking history. Lung cancer developed in 356 (6.9%) of the 5180 patients. The overall annual incidence of lung cancer remained relatively constant between approximately 1.0% and 2.0% during the 15 years of follow-up. Men had an increased risk of lung cancer compared with women (relative risk [RR] = 1.56; 95% confidence interval [CI] = 1.18 to 2.03). Compared with patients with oral cavity cancer (RR = 1.00), the relative risk of lung cancer developing by the site of the index tumor was 0.63 (95% CI = 0.40 to 0.98) for lip, 1.12 (95% CI = 0.81 to 1.56) for intrinsic larynx, 1.73 (95% CI = 1.21 to 2.47) for oropharynx, 1.84 (95% CI = 1.16 to 2.92) for hypopharynx, and 2.28 (95% CI = 1.60 to 3.24) for extrinsic larynx. Among the 522 patients who were interviewed, men smoked more than women ( p < 0.0001), and patients with laryngeal or pharyngeal cancer smoked more than patients with cancer of the lip or the oral cavity ( p < 0.05). Among patients with head and neck cancer, the risk of lung cancer is highest for men and for patients with cancer of the pharynx or extrinsic larynx. These findings may be explained by differences in smoking consumption. (Otolaryngol Head Neck Surg 1997;116:630-6.)     

Dopamine receptor agonists alter gap prestimulus modulation

An innocuous sensory event (a prestimulus) that briefly precedes a startle-eliciting stimulus (SES) will reduce the amplitude of the subsequently elicited reflex. In three experiments brief silent periods in otherwise continuous noise (gaps) were used as prestimuli to investigate the effects of the D₁ dopamine receptor agonist (±)-SKF-38393 (SKF) and the dopamine D₂ receptor group agonist (−)-quinpirole hydrochloride on gap inhibition of the rat’s acoustic startle reflex. Gap durations of 4 and 50 ms were analyzed. Quinpirole (0–1.6 mg/kg) had a biphasic effect on gap inhibition. Lower doses increased gap inhibition, an effect that peaked at the 0.4 mg/kg dose. For higher doses, inhibition returned to control levels for the 4-ms long gap, but remained elevated for the 50-ms long gap. SKF had no effect on gap inhibition, and haloperidol (0.2 mg/kg) reversed the quinpirole-induced increase of gap inhibition. These data implicate the D₂ dopamine receptor group in gap inhibition of startle modulation. The results are discussed in terms of the effects of catecholamine agonists on attention. Received: 25 July 1995/Final version: 28 April 1997     

Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.