Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat?

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS. RESULTS: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS. CONCLUSIONS: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made.

High affinity binding of 125I-labeled human tumor necrosis factor (LuKII) to specific cell surface receptors.

125I-labeled TNF(LuKII) (tumor necrosis factor) binds specifically to human and mouse cell lines sensitive to the cytotoxic effect of TNF, but not to cells made resistant to TNF. TNF-sensitive cells have cell surface receptors with a high affinity for TNF(LuKII). Mouse TNF competes with TNF(LuKII) for receptor binding. Scatchard analysis of the binding data yielded linear plots and suggests that TNF(LuKII) binds to homogeneous receptor sites. The number of TNF(LuKII) receptors on two TNF-sensitive cell lines is 200-300 per cell and the affinity constant of the receptor for TNF(LuKII) is approximately 1 X 10(-10) M.

Nonhematopoietic cells selected for resistance to tumor necrosis factor produce tumor necrosis factor.

TNF-resistant lines of L cells can be derived from TNF-sensitive populations by repeated exposure to TNF, and these resistant L cells, in contrast to sensitive L cells and other types of cells, lack demonstrable cell surface receptors for TNF. We have now found that TNF-resistant L cells produce a factor that is cytotoxic for L cells and has the following distinguishing characteristics of mouse TNF: it is a protein of 43 kD, composed of 16 kD subunits, that competes with TNF for receptor binding, induces hemorrhagic necrosis of the TNF-sensitive mouse sarcoma Meth A, has synergistic cytotoxic action with interferon, and its activity is neutralized by antibody to TNF. The two conclusions of this study are that cells selected for TNF resistance spontaneously produce a molecule resembling macrophage TNF, and that cells of nonhematopoietic origin are capable of producing TNF.

Expression of rod and cone visual pigments in goldfish and zebrafish: a rhodopsin-like gene is expressed in cones.

The primary purpose of the present study was to determine whether a rhodopsin-like gene, which has been postulated to represent the green cone pigment in several species, is in fact expressed in cone photoreceptors instead of rods. The expression patterns of rod opsin and blue and red cone opsins were also examined in both goldfish and zebrafish retinas using colorimetric in situ hybridization. The results demonstrate that the rhodopsin-like gene is expressed in green cones, as predicted. A subset of small cones that do not hybridize with these cRNA probes are tentatively identified as ultraviolet receptors. The results also demonstrate that opsin message in cones is restricted to the perinuclear region, whereas in rods, it is both perinuclear and adjacent to the ellipsoid.

Infant dietary experience and acceptance of solid foods.

OBJECTIVE: To examine the effects of dietary experience and milk feeding regimen on acceptance of their first vegetable by 4- to 6-month-old infants. DESIGN: Longitudinal study, of 26-days duration, observing infants aged 4 to 6 months at the start of the study. Random assignment to treatments, within-subject control. SETTING: General community in a medium-sized midwestern town. SUBJECTS: Thirty-six infants and their mothers. Subjects were solicited through birth records and advertisements in local newspapers. INTERVENTIONS: Infants were randomly assigned to be fed one vegetable on 10 occasions, either salted or unsalted peas or green beans, for a 10-day period. OUTCOME MEASURES: Infant intake of the vegetable consumed during the 10-day exposure period; intake of salted and unsalted versions: (1) before the 10-day exposure period, (2) immediately after the exposure period; and (3) after a 1-week period of delay. Intake of a control food was also measured before and after repeated consumption of the vegetable. Adult ratings of the infants' videotaped responses during test feedings were also obtained before and after the exposure period. RESULTS: After 10 opportunities to consume the vegetable, all infants significantly increased their intake (P < .001). Although they did not differ initially, infants fed breast milk showed greater increases in intake of the vegetable after exposure and had an overall greater level of intake than formula-fed infants. Adult ratings of the infants' nonverbal responses correlated positively with infant intake. CONCLUSIONS: Infants increase their acceptance (reflected both in changes in intake and in behavioral response) of a novel food after repeated dietary exposure to that food. Relative to formula-feeding, breast-feeding may facilitate the acceptance of solid foods.

Surgical debulking of eyelid and anterior orbital plexiform neurofibromas by means of the carbon dioxide laser.

PURPOSE: To present the carbon dioxide laser as an effective tool for surgical debulking of eyelid and orbital neurofibromas. METHOD: Two patients with neurofibromatosis underwent surgical debulking of their eyelid and orbital plexiform neurofibromas by means of the carbon dioxide laser. RESULTS: Acceptable cosmetic results were obtained with the removal of eyelid and orbital neurofibromas with improved hemostasis and minimal destruction of surrounding tissue when compared with conventional methods of removal. CONCLUSIONS: The carbon dioxide laser may allow significant improvement in the removal of plexiform neurofibromas.

Behaviors induced by 5-hydroxytryptophan in neonatal, preweaning, postweaning, and adult Sprague-Dawley rats.

The behaviors induced by the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) has been called the "5-HT (serotonin) syndrome." These behaviors and others identified in rat pups were observed following administration of 5-HTP (300 mg/kg, SC) on postnatal (PN) days 3, 14, and 28 and in adult rats. Certain 5-HT syndrome behaviors and other uniquely neonatal behaviors were present in PN3 pups treated with vehicle. 5-HTP-treated PN3 pups showed increased head-shakes, rollovers, vocalizations, and forepaw treading and decreased hindlimb abduction. No 5-HT syndrome or neonatal behaviors were present at PN14 or PN28 or in adults treated with vehicle. 5-HTP administered at PN14 stimulated circling, forepaw treading, and resting tremor; at PN28, stimulated head-shakes and resting tremor; and in adults produced only head-shakes. To determine if prior exposure to 5-HTP affected the sensitivity of 5-HT receptor subtypes, the 5-HT1A agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and the 5-HT2/1C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were administered to all rats as adults. 8-OH-DPAT (1 mg/kg, SC) produced flattened body posture unaffected by prior exposure to 5-HTP. Head-shakes induced by DOI (5mg/kg, IP) were decreased by prior exposure to 5-HTP at PN3 and adult, but increased by preexposure at PN28. Thus, serotonergic neural systems are implicated in some behaviors of neonates. The developmental patterns suggest changes in the sensitivity to these systems. Further, lasting changes in 5-HT2/1C receptor sensitivity occur due to exposure to 5-HTP.

Luteinizing hormone response to controlled-release deslorelin in estradiol benzoate primed ovariectomized gilts.

Development of a controlled release formulation of gonadotropin releasing hormone that would stimulate a LH surge capable of reducing the time span of ovulations would greatly benefit reproductive management because a single timed insemination could be used. A dose-response study was conducted to determine if Deslorelin, a potent gonadotropin releasing hormone analogue, delivered via the SABER system, a biodegradable controlled release system, would stimulate an ovulatory-like LH surge in the pig. Twenty ovariectomized gilts, approximately 200 d old and 100 kg body weight (BW), received estradiol benzoate (15 microg/kg BW im) and 48 h later, the gilts were given deslorelin at 0, 12.5, 25.0, 50.0 or 100.0 microg im (n = 4 each treatment group). Compared to controls, mean blood deslorelin concentrations were still elevated at 30 h after deslorelin. Mean deslorelin magnitude, area under the curve and duration were sequentially greater (P<0.05) in a dose-dependent sequence. Compared to controls, serum LH concentrations were elevated (P<0.05) for 6 to 12 h after deslorelin. A dose-response relationship was absent for all parameters of LH secretion. Magnitude of the serum LH response was greatest (P<0.05) in the 12.5 microg and 50.0 microg groups, whereas area under the curve was lower (P<0.05) after 25.0 microg of deslorelin than after 12.5, 50.0 and 100.0 microg, which were not different from each other. Thus, no more than 12.5 microg of deslorelin is necessary to obtain maximum LH release in the model studied and doses less than 12.5 microg may also be effective.

Measuring the intelligence of college students with learning disabilities: a comparison of results obtained on the WAIS-R and the KAIT.

This study compared results obtained on the Wechsler Adult Intelligence Scale-Revised and the Kaufman Adolescent Test and Adult Intelligence; these tests were individually administered to college students with and without learning disabilities. Participants were 30 students with learning disabilities and 30 students without learning disabilities between the ages of 18 and 30. Students were administered both IQ tests and the Peabody Picture Vocabulary Test-Revised, used as a covariate measure. The results were analyzed through a repeated-measures analysis of variance. No significant differences were found between groups or between tests. A significant difference was found for both groups when Performance IQ and Fluid Scale scores were compared.

CD93 and related family members: their role in innate immunity.

CD93 belongs to a newly described family of transmembrane glycoproteins which also includes endosialin and thrombomodulin. These cell surface proteins are grouped into a family based on similar ectodomain architecture consisting of a C-type lectin-like domain, a series of EGF-like repeats and a highly glycosylated mucin-like domain. However, recent studies suggest overlapping functions in the regulation of processes involving innate immunity and inflammation. CD93 regulates phagocytosis of apoptotic cells in vivo, a function critical to development, tissue repair and maintenance of tissue homeostasis. In addition, in vitro studies have demonstrated a role for CD93 in phagocytosis of antibody and complement opsonized particles and also in leukocyte and endothelial cell adhesion. Analysis of CD93 expression on endothelial cells in the developing mouse embryo correlates with the remodeling of blood vessels suggesting a role for CD93 in regulating angiogenesis, a process tightly linked to acute and chronic inflammation and also required for tumor metastasis. Endosialin has been characterized as a tumor specific antigen and functions in angiogenesis. Thrombomodulin is best characterized as a natural anticoagulant; however, more recent reports have illuminated the importance of thrombomodulin in the regulation of inflammation. This review discusses similarities and differences in the family members, and focuses on known and speculated functions in regulation of innate immunity.

The DEBIT trial: an intervention to reduce antipsychotic polypharmacy prescribing in adult psychiatry wards - a cluster randomized controlled trial.

BACKGROUND: Clinical guidelines advise against prescribing more than one antipsychotic with limited exceptions. Despite this, surveys continue to report high antipsychotic polypharmacy rates. The aim of the study was to investigate the effectiveness of a multi-faceted intervention in reducing prescribing of antipsychotic polypharmacy on general adult psychiatry wards, compared with guidelines alone. METHOD: A pragmatic cluster randomized controlled trial recruited 19 adult psychiatric units (clusters) from the South West of England. Participants were all ward doctors and nurses. The multi-faceted intervention comprised: an educational/CBT workbook; an educational visit to consultants; and a reminder system on medication charts. RESULTS: The odds of being prescribed antipsychotic polypharmacy in those patients prescribed antipsychotic medication was significantly lower in the intervention than control group when adjusted for confounders (OR 0.43, 95% CI 0.21-0.90, p=0.028). There was considerable between-unit variation in polypharmacy rates and in the change in rates between baseline and follow-up (5 months after baseline). CONCLUSION: The intervention reduced levels of polypharmacy prescribing compared to guidelines alone although the effect size was relatively modest. Further work is needed to elicit the factors that were active in changing prescribing behaviour.

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Complications of laser resurfacing and their management.

PURPOSE: To describe complications associated with laser resurfacing along with specific treatment recommendations. METHODS: The authors' experiences with laser resurfacing complications are discussed in conjunction with a review of published reports. Current preoperative and postoperative regimens are also presented. RESULTS: Postoperative erythema occurs in all patients and is considered a transient side effect, not a complication. Postinflammatory hyperpigmentation, hypopigmentation, scarring, wound infections, milia, ectropion, pain, acneiform eruptions, pruritus, and contact dermatitis are reported by multiple authors. Specific interventions combined with the passage of time allow most of these complications to resolve, leaving the patient with an acceptable final result. CONCLUSIONS: Although laser resurfacing is a safe and effective method of facial rejuvenation, the cosmetic surgeon must be aware of the various complications that may be encountered. Prompt recognition of complications and appropriate management provide the best opportunity for an acceptable aesthetic outcome.

Developing condition-specific measures of functional status and well-being for children.

This paper describes the American Academy of Pediatrics' program to develop several condition-specific measures to assess the functional status and well-being of children with chronic conditions. The development of a measure for children between 5 and 12 years of age with asthma serves as a template for the development of measures for other conditions and is the focus of this paper. The processes followed in the drafting of content, refinement, and pilot testing of the measure are discussed in this paper. The domains addressed in the asthma measure include physical symptoms; the child's physical activity; the child's social activity; the family's social activity; the emotional impact on the child; the emotional impact on the family; and health care utilization. Each domain is represented by a subscale in the measure. Content for individual items within subscales was established by conducting focus groups with parents and physicians and by reviewing the literature. The measure was tested through an in-depth cognitive interview process and pilot tested by administering the measure to 95 parents of children with mild, moderate, and severe asthma. Five of the seven subscales had acceptable internal consistency reliability as measured by coefficient alpha. Construct validity was shown for some scales by significantly different scores for children with mildly versus moderately severe asthma.

Comparative survival of antibiotic-resistant and -sensitive fecal indicator bacteria in estuarine water.

The survival of antibiotic-resistant and -sensitive strains of Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Streptococcus equinus, and two environmental isolates, AP17 and AQ62, was examined in estuarine water. Each strain was rendered resistant to a combination of two antibiotics by serial passage in increasing concentrations of antibiotics. Cultures were incubated in filter-sterilized estuarine water for up to 7 days. Recovery was assessed by examining colony-forming ability on media with and without antibiotics. None of the antibiotic-resistant forms survived longer than its antibiotic-sensitive counterpart in estuarine water. Three of the resistant strains died off more rapidly than the antibiotic-sensitive wild type. Survival of the test bacteria in estuarine water was as follows: sensitive and resistant AQ62, resistant Escherichia coli less than sensitive Escherichia coli less than resistant AP17 less than resistant Enterococcus faecium less than sensitive AP17, sensitive and resistant S. equinus less than sensitive and resistant Enterococcus faecalis, sensitive Enterococcus faecium. The results supported the suggestion that fecal entercocci may serve as better indicators of fecal pollution than Escherichia coli in marine ecosystems. Moreover, the results indicated that the use of antibiotic-resistant mutants to follow the fate of bacteria in the environment is inappropriate without adequate studies to ensure that resistant and wild-type strains react similarly to environmental stressors.