Examination of a distress screening intervention for rural cancer survivors reveals low uptake of psychosocial referrals.

PURPOSE: To determine the impact of a telemedicine-delivered intervention aimed at identifying unmet needs and cancer-related distress (CRD) following the end of active treatment on supportive care referral patterns. METHODS: We used a quasi-experimental design to compare supportive care referral patterns between a group of rural cancer survivors receiving the intervention and a control group (N = 60). We evaluated the impact of the intervention on the number and type of referrals offered and whether or not the participant accepted the referral. CRD was measured using a modified version of the National Comprehensive Cancer Network Distress Thermometer and Problem List. RESULTS: Overall, 30% of participants received a referral for further post-treatment supportive care. Supporting the benefits of the intervention, the odds of being offered a referral were 13 times higher for those who received the intervention than those in the control group. However, even among the intervention group, only 28.6% of participants who were offered a referral for further psychosocial care accepted. CONCLUSIONS: A nursing telemedicine visit was successful in identifying areas of high distress and increasing referrals. However, referral uptake was low, particularly for psychosocial support. Distance to care and stigma associated with seeking psychosocial care may be factors. Further study to improve referral uptake is warranted. IMPLICATIONS FOR CANCER SURVIVORS: Screening for CRD may be inadequate for cancer survivors unless patients can be successfully referred to further supportive care. Strategies to improve uptake of psychosocial referrals is of high importance for rural survivors, who are at higher risk of CRD.

Beyond broadband: digital inclusion as a driver of inequities in access to rural cancer care.

PURPOSE: Rural cancer survivors have worse quality of life than their urban counterparts. Telemedicine is a potential solution to connecting rural residents with specialized cancer providers during the survivorship period, but limitations in broadband may stifle the impact. Using data from a feasibility study evaluating a telemedicine intervention aimed at connecting rural Virginia cancer survivors with their care team located at a cancer center associated with an academic medical center, we sought to evaluate the ability of rural survivors to access the intervention and suggest strategies for improving access to rural cancer survivorship care. METHODS: We used a descriptive design with geospatial and quantitative methods to understand broadband access, driving time to a satellite telemedicine site, and ability to utilize a borrowed cellular-enabled tablet to participate in the intervention for cancer survivors living in Central Virginia. RESULTS: Our study participants resided in census tracts where an average of 58% of households have adequate broadband access necessary to support a telemedicine videoconferencing intervention. Average driving time to the nearest telemedicine site was 29.6 min. Those who utilized the borrowed tablet experienced considerable difficulty with utilizing the technology. CONCLUSIONS: Rural cancer populations do not have equal access to a cancer survivorship telemedicine intervention. IMPLICATIONS FOR CANCER SURVIVORS: Telemedicine interventions aimed at connecting cancer survivors with their academic medical center-based cancer providers may be ineffective if survivors do not have access to either fixed broadband or a satellite clinic. Future research needs to evaluate other sites from which rural survivors can connect, such as rural public libraries.

Regulation of cementoblast gene expression by inorganic phosphate in vitro.

Examination of mutant and knockout phenotypes with altered phosphate/pyrophosphate distribution has demonstrated that cementum, the mineralized tissue that sheathes the tooth root, is very sensitive to local levels of phosphate and pyrophosphate. The aim of this study was to examine the potential regulation of cementoblast cell behavior by inorganic phosphate (P(i)). Immortalized murine cementoblasts were treated with P(i) in vitro, and effects on gene expression (by quantitative real-time reverse-transcriptase polymerase chain reaction [RT-PCR]) and cell proliferation (by hemacytometer count) were observed. Dose-response (0.1-10 mM) and time-course (1-48 hours) assays were performed, as well as studies including the Na-P(i) uptake inhibitor phosphonoformic acid. Real-time RT-PCR indicated regulation by phosphate of several genes associated with differentiation/mineralization. A dose of 5 mM P(i) upregulated genes including the SIBLING family genes osteopontin (Opn, >300% of control) and dentin matrix protein-1 (Dmp-1, >3,000% of control). Another SIBLING family member, bone sialoprotein (Bsp), was downregulated, as were osteocalcin (Ocn) and type I collagen (Col1). Time-course experiments indicated that these genes responded within 6-24 hours. Time-course experiments also indicated rapid regulation (by 6 hours) of genes concerned with phosphate/pyrophosphate homeostasis, including the mouse progressive ankylosis gene (Ank), plasma cell membrane glycoprotein-1 (Pc-1), tissue nonspecific alkaline phosphatase (Tnap), and the Pit1 Na-P(i) cotransporter. Phosphate effects on cementoblasts were further shown to be uptake-dependent and proliferation-independent. These data suggest regulation by phosphate of multiple genes in cementoblasts in vitro. During formation, phosphate and pyrophosphate may be important regulators of cementoblast functions including maturation and regulation of matrix mineralization.

Effects of activated macrophages and fibroblast growth factor on random skin flap survival in swine.

OBJECTIVE: To examine the effect of application of activated autologous macrophages and basic fibroblast growth factor (FGF) on random skin flap survival in swine. DESIGN: A randomized nonblinded controlled trial. According to a standard design, six dorsally based, random-pattern skin flaps were raised in each of 12 Yorkshire pigs. METHODS: Twenty-five milliliters of blood is harvested from each animal 20 to 24 hours prior to flap creation. Monocytes are isolated, placed in culture medium, and then activated by the addition of platelet-derived growth factor (PDGF) and tissue growth factor beta (TGF-alpha). Following an 18-hour incubation period, the monocytes are decanted and quantified, and their viability confirmed. These cells are then infused into the wound bed of the treatment flaps immediately following flap creation, and FGF is added prior to flap closure. The position of treatment and control flaps is systematically varied with regard to anterior-to-posterior and side-to-side flap positions within each animal. The area of superficial flap necrosis is evaluated on postoperative day 7, digitally scanned, and analyzed using graphics software. Control flaps are elevated similarly, but receive no placebo treatment. RESULTS: Two-way analysis of variance (ANOVA) demonstrated nonsignificant differences between pig side and anterior, middle, and posterior flap positions within treatment and control flap groups. Using side and position pooled data, a one-way ANOVA showed no statistically significant differences between treatment and control flaps. CONCLUSIONS: The cellular and biochemical events following creation of a surgical wound are complex and incompletely understood. Our attempt to augment the natural role of the macrophage in wound healing by employing cytokines to activate these cells and to accelerate their arrival by implanting them into the wound bed failed to enhance flap survival. Further study is warranted to ascertain the details of wound healing, particularly with respect to cytokine concentrations and the timing of their roles, if we are to find a clinically applicable means of enhancing flap survival.

The septum in rhinoplasty.

Recognition and correction of septal abnormalities in rhinoplastic surgery has been a constant evolution aided by the development of an in depth anatomic understanding of the nose and the refinement of techniques based on the pertinent anatomy. Whether the deformity presents a functional, aesthetic, or combined problem, the authors prefer a single stage technique that separates the structural components of the nose, isolating the deformities present, and then reconstructing the components to effect a desirable result in terms of airway and appearance. Although no two nasal surgeries are identical, there are characteristic deformities that are noted to be generally more problematic. We briefly review normal septal anatomy as it pertains to the septorhinoplasty operation and then discuss our approach to specific septal variations that we have found to have a significant impact with regard to achieving satisfactory functional and aesthetic results.

Steroid use in rhinoplasty: an objective assessment of postoperative edema.

The objective of this study was to measure the effect of a single, preoperative 10 mg dose of dexamethasone on postoperative edema associated with rhinoplasty. This was a randomized, double-blind prospective study conducted in a military academic tertiary referral center. Twenty men, aged 18 to 45 years, were enrolled in the study over 28 months. All 20 men underwent rhinoplasty with osteotomy. Preoperative magnetic resonance imaging scans were obtained on the morning of surgery and postoperative scans were obtained within 48 hours. Postoperative edema was quantified as the difference in soft tissue thickness (mm) between the pre- and postoperative scans. Contrary to our expectations, the rhinoplasty patients who received dexamethasone had increased postoperative edema (p < 0.02) when compared to patients not receiving dexamethasone. This is the first objective, double-blind study that shows an increase in postoperative edema after rhinoplasty with a single preoperative dose of dexamethasone.

The effects of macrophages on the survival of random skin flaps in swine.

Tissue macrophages play a critical role in neovascularization by releasing angiogenic cytokines. Macrophages normally arrive into a wound bed 48 to 96 hours following an injury. Introducing macrophages into a wound bed at the time of closure would theoretically stimulate neovascularization in the traumatized tissue prior to what is normally observed. The ability to promote early angiogenesis could be an important factor in the survival of an extended skin flap. By taking advantage of advanced cell-sorting techniques, the authors developed the first study to evaluate the effect of placing a purified autologous macrophage population into an extended skin flap. We created 72 dorsally based random skin flaps in Yorkshire pigs; 48 of these wounds received autologous macrophages while 24 flaps served as controls. The macrophages were obtained by utilizing monoclonal antibodies in conjunction with flow cytometry. The skin flaps were evaluated on postoperative day 6 for their viability. Analysis of the data showed no statistically significant difference between the control and treatment flaps. There was, however, a trend of increased survival for flaps treated with macrophages. This is the first study to investigate using a purified population of cells to improve the survival of random skin flaps.

Soluble factors secreted by activated T-lymphocytes modulate the transcription of the immunosuppressive cytokine TGF-beta 2 in glial cells.

Coordination of the immune response to injury or disease in the brain is postulated to involve bi-directional discourse between the immune system and the central nervous system. This cross communication involves soluble mediators, including various growth factors, cytokines, and neuropeptides. In this report, we demonstrate that the supernatant from activated T-lymphocytes is able to induce the transcription of a potent cytokine, TGF-beta 2 in glial cells. The activating stimulus invokes signaling mechanisms distinct from known kinase or protease pathways. Activation of TGF-beta 2 transcription correlates with the loss of binding activity for an 80 kDA glial labile repressor protein, GLRP, to a responsive region within the TFG-beta 2 promoter. Although GLRP shares some characteristics with the inducible transcription factor AP-1, it appears to be distinct from known AP-1 family members. These data along with previous observations demonstrating the potent immunosuppressive activity of TGF-beta 2, support a model for a feedback mechanism between the activated T-lymphocytes and astrocytes via TGF-beta 2 to regulate the immune response.

Differential regulation of transforming growth factor beta-1 gene expression by glucocorticoids in human T and glial cells.

The inflammatory process in the brain requires bidirectional interaction of the immune and nervous systems. Evidently, astrocytic glial cells play an important role in facilitating this communication by releasing immunomodulators and cytokines. Expression of transforming growth factor beta-1 (TGF beta-1), a potent inhibitor of T cell function and glial cell proliferation, is highly regulated in T cells and is believed to be an important component in the molecular interaction between the immune and nervous systems. Comparative analysis of TGF beta-1 gene expression in human T and glial cells by Northern hybridization and S1 nuclease protection assay showed that dexamethasone (DM) caused a significant decrease in the basal and PMA-induced levels of TGF beta-1 mRNA in glial cells but not in T cells. This reduction correlated with a lower level of TGF beta-1 protein production. Transient transfection assay using deletion constructs of the 5' TGF beta-1 gene promoter-containing sequences between -453 and +11 bp identified a region spanning -160 to -60 bp as a potential sequence responsive to regulation by DM in T cells, whereas in glial cells, the overall transcriptional activity of the 5' TGF beta-1 promoter was reduced after DM treatment, but promoter activity within each construct remained constant in response to DM. Thus, a DM-responsive region could not be identified within the TGF beta-1 promoter in glial cells. These findings suggest that TGF beta-1 gene expression is differentially regulated by distinct regulatory elements in T and glial cells, and that extracellular stimulators, including glucocorticoids, can utilize the TGF beta-1-regulatory pathway to affect the functions of neural and immune cells.

The extended Abbé flap.

Large upper lip defects that include the surrounding aesthetic subunits of the midface are difficult to reconstruct. Abbé flaps have been a popular method of dealing with small upper lip defects but, as classically described, they are insufficient for larger defects. We performed cadaver injections to evaluate the vascular territory supplied by the inferior labial artery with particular attention to the submental area. Extended Abbé flaps were then designed and used in combined upper lip and midfacial reconstruction. Three cases and guidelines for the use of the extended Abbé flap are presented.

Evidence for stimulation of the transforming growth factor beta 1 promoter by HIV-1 Tat in cells derived from CNS.

Infection by human immunodeficiency virus type 1 (HIV-1), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is often complicated with a high incidence of neurologic disorders. It is believed that HIV-1, in addition to infecting both macroglial and microglial cells, may influence the expression of several strategic genes of uninfected neighboring or latently infected brain cells. It is suspected that the viral-encoded transregulatory protein, Tat, facilitates cross-communications between these cells. In support of this concept, earlier studies demonstrated that Tat is released from the infected cells, and has the capacity to be taken up by the uninfected cells and exert its biological activity on the responsive gene. Recent studies in several laboratories suggest the involvement of Tat in altering the expression of a limited number of cellular regulatory factors which, in turn, may mediate the altered physiology of the cells. In this communication, we demonstrate the ability of the HIV-1 Tat protein to increase expression of transforming growth factor beta 1 (TGF-beta 1), a cytokine with potent immunosuppressive activity, in human astrocytic glial cells. Implications of the Tat-mediated induction of TGF-beta 1 expression and cytokine involvement in the regulation of immune response and central nervous system (CNS) pathology are discussed.

Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells.

The Tat protein of human immunodeficiency virus type 1 has been increasingly implicated in directly contributing to the disease AIDS by altering the expression of strategic cellular genes. In this study we demonstrate that the presence of the human immunodeficiency virus type 1 regulatory protein Tat is associated with a significant induction in the expression of certain protein components of the extracellular matrix in glial-derived cells. Northern blot analysis reveals that in cells expressing Tat there is a marked elevation in the steady-state RNA levels for fibronectin and types I and III collagen. Metabolic labeling of the Tat-producing cells demonstrates that this induction is also reflected at the level of protein synthesis. Transient transfection experiments indicate that the presence of Tat results in increased transcription of fibronectin and alpha I type I collagen promoters. Possible mechanisms for this phenomenon and their significance with regard to AIDS are discussed.

A case-control study of persons with elevated blood levels of dieldrin.

Twenty-seven pesticide workers with elevated blood levels of dieldrin (greater than or equal to 15 ppb) were involved in a case-control study which included history and physical examination, comprehensive neurological evaluation, laboratory tests, and psychological and psychomotor testing. No clinically important differences were found on history, physical, specialized neurological tests, or laboratory examination. The exposed group showed a statistically significant difference in five out of 58 psychological (P) and psychomotor (PM) tests--at least three would be expected by chance (p less than or equal to .05). In only one of these tests was there any significant correlation with dieldrin levels. Even though the exposed group had worse scores than the control group in 47 of 58 P--PM tests, such scores were, with a few exceptions, in the normal range of values. Elevated blood levels of dieldrin encountered in this study do not appear to have any chronic deleterious effects on health, as measured by conventional medical work-up and extensive central nervous system testing.

Menetrier's disease in a rhesus monkey (Macaca mulatta).

Gross and microscopic features closely resembling those found in Menetrier's disease in man are described in a 20-month-old rhesus monkey. The gastric lining was characterized by greatly enlarged rugae caused by mucosal hypertrophy and hyperplasia along with outfolding of the muscularis mucosa and the submucosa. The mucosa and submucosa were infiltrated with inflammatory cells, mainly lymphocytes and plasma cells.

Strongyloidiasis in an infant orangutan (Pongo pygmaeus).

Necropsy of a 15-month-old male orangutan (Pongo pygmaeus) showed multiple nodular elevations of the mucosa of the colon, petechial hemorrhages in both lungs, and mucosal ulcerations in the cecum, appendix, and proximal colon. Light microscopy revealed filariform larvae of Strongyloides in the lung, colon, and mesenteric lymph nodes. Rhabditiform larvae were also observed in sections of colon.