GeoHealth Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science.

GeoHealth research both characterizes and predicts problems at the nexus of earth and human systems like climate change, pollution, and natural hazards. While GeoHealth excels in the area of integrated science, there is a need to improve coordinated and networked efforts to produce open science to enable environmental justice. There is a need to resource and empower frontline populations that are disproportionately marginalized by environmental injustice (i.e., the unequal protection from environmental harms and lack of access and meaningful engagement in decision making for a healthy environment; EPA, 2022, https://www.epa.gov/environmentaljustice). GeoHealth practice has the opportunity to advance environmental justice or the "fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income" with respect to how research and collaboration of GeoHealth professionals supports the "development, implementation, and enforcement of environmental laws, regulations, and policies" that produce equal protection from environmental and health hazards and access to the decision making for a health environment (EPA, 2022, https://www.epa.gov/environmentaljustice). Here we highlight barriers and opportunities to apply an equity-centered ICON framework to the field of GeoHealth to advance environmental justice and health equity.

Antigenic cross-reactivity between adenocarcinoma of the breast and fibrocystic disease of the breast.

Peripheral lymphocytes obtained from 12 of 13 patients who had fibrocystic disease (FCD) of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. Sera from 6 women with active FCD or metastatic breast cancer could specifically block the cytotoxicity of lymphocytes from either population of patients against cancer cells. This implied extensive antigenic cross-reactivity between benign and malignant hyperplastic disease of the breast. Sera from 4 individuals clinically free of FCD or breast fibroadenoma (FAD) neutralized the blocking activity in the sera of patients with metastatic breast cancer. Patients "cured" of FCD or FAD represented a pool of potential plasma donors for immunotherapy of recurrent breast cancer.

Milk lipid digestion in the neonatal dog: the combined actions of gastric and bile salt stimulated lipases.

Intragastric lipolysis may be particularly important for the digestion of milk lipid since milk fat globules are resistant to pancreatic lipase without prior disruption; milk bile salt stimulated lipase (BSSL) may supplement further intestinal hydrolysis. Previous information on gastric lipolysis has been based primarily on in vitro studies using artificial lipid emulsions containing a single component fatty acid and have focused on the preferential release of medium-chain fatty acids. The actual contribution of these enzymes to overall fat digestion in vivo on natural substrates has rarely been studied, however. The neonatal dog is an excellent model in the study of lipid digestion because, like the human, milk lipids are high in long-chain unsaturated fatty acids, milk contains BSSL and gastric lipase is the predominant lipolytic enzyme acting in the stomach. We used a combination of in vivo studies with in vitro incubations to investigate digestion of milk lipid by gastric and milk (BSSL) lipases in the suckling dog. In the first 4 weeks postpartum, 14-41% and 42-60% of milk triacylglycerol was hydrolyzed to primarily diacylglycerol and free fatty acid (FFA) in the first 30 and 60 min in the stomach, respectively. Milk lipid contained high levels (63%) of long-chain unsaturated fatty acids, which were preferentially released as FFA during in vivo gastric lipolysis, consistent with the actions and stereospecificity of gastric lipase. While levels of hydrolysis in gastric aspirates were significantly different (by age and time in stomach) at the start of in vitro studies, total hydrolysis in all incubation systems plateaued at about 65%, suggesting product inhibition by the long-chain FFA, but to a much lesser degree than previously expected from in vitro studies. The magnitude of in vivo intragastric lipolysis was 3- to 6-times greater than that predicted by in vitro assays using either milk lipid or labeled emulsion as substrate, respectively. Prior exposure to intragastric lipolysis resulted in 30% hydrolysis by BSSL compared to 5% hydrolysis without prior exposure. We suggest that previous in vitro studies have largely underestimated the actual degree of intragastric lipolysis that can occur and its activity on long-chain fatty acids; this study indicates the importance of the combined mechanisms of gastric lipase and BSSL to fat digestion in the suckling neonate.

Poly I:C induces development of diabetes mellitus in BB rat.

Polyinosinic polycytidilic acid (poly I:C), an inducer of alpha-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10-treated DR and poly-5-treated DP rats. A significant degree of insulitis occurred in all the poly I:C-treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C- and saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Preclinical safety evaluation of G207, a replication-competent herpes simplex virus type 1, inoculated intraprostatically in mice and nonhuman primates.

G207, a replication-competent herpes simplex virus type 1 (HSV-1) virus, has been previously shown to be effective against human prostate cancer xenografts in mice. This study assesses its safety in the prostate of two animal models known for their sensitivity to HSV-1. BALB/c mice were injected intraprostatically with either HSV-1 G207 or strain F and observed for 5 months. None of the G207-injected animals exhibited any clinical signs of disease or died. However, 50% of strain F-injected mice displayed sluggish, hunched behavior and died by day 13. Histopathologically, the G207-injected prostates were normal whereas strain F-injected prostates showed epithelial flattening, sloughing, and stromal edema. Four Aotus nancymae monkeys were also injected with G207 intraprostatically and observed short term (up to 21 days) and long term (56 days). Safety was assessed on the basis of clinical observations, viral biodistribution, virus shedding, and histopathology. None of the injected monkeys displayed evidence of clinical disease, shedding of infectious virus, or spread of the virus into other organs. Except for minor histological changes unrelated to the study, no significant abnormalities were observed. These results demonstrate that G207 can be safely inoculated into the prostate and should be considered for human trials for the treatment of prostate cancer.

The role of computed tomography in the evaluation of post-mastectomy locally recurrent breast cancer.

The rate of post mastectomy local-regional recurrence of breast cancer has remained in the range of 10-30% for decades. The traditional treatment, external beam radiation therapy, is successful in eradicating local disease in most cases, but re-recurrences are seen in about 50% of patients. Since 1982, 33 patients with such recurrences have undergone evaluation with computed tomography (CT) at our institution as part of their diagnostic work-up. In 22/33 (67%), CT revealed unsuspected disease, and in 10 of these patients the radiation treatment plan had to be altered. These results, similar to three other published series, strongly suggest that CT is a necessary part of the work-up of patients with post-mastectomy local-regional recurrences. The significance of these findings with respect to the cause of post mastectomy local-regional failures is further discussed.

A phase I study of combined UFT plus leucovorin and radiotherapy for pancreatic cancer.

PURPOSE: This Phase I study combines tegafur and uracil (UFT) with leucovorin and conventional radiation for the treatment of pancreatic cancer. The design seeks to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of this regimen as well as to define a future Phase II dose level. METHODS: Patients with locally advanced and unresectable pancreatic cancer were treated with 45 Gy of radiation therapy. The initial UFT dose was 150 mg/m(2)/day given with leucovorin 90 mg/day, both divided into 3 daily doses for 35 days concurrent with radiation. UFT doses were escalated at increments of 50 mg/m(2)/day. Dose-limiting toxicity (DLT) was defined as Grade 3 or greater nausea, vomiting or diarrhea despite medical intervention; or Grade 3 or greater neutropenia/thrombocytopenia; or Grade 3 or greater hepatic toxicity; or inability of the patient to take 75% or more of the planned UFT/leucovorin; or radiotherapy interruption of greater than 1 week. The MTD for UFT/leucovorin was exceeded by one dose level when a certain dose caused DLT in 2 or more patients of 6. RESULTS: Five evaluable patients had Stage I resectable disease but had pathologic adenopathy. Seven had Stage II unresectable disease. Compliance with therapy was excellent. At a daily dose of 300 mg/m(2) of UFT, we noticed minimal diarrhea and hematologic toxicity with mild-moderate nausea, anorexia, and fatigue. Three patients had Grade 4 toxicity: 1 had neutropenia on Day 38, 1 had diarrhea on Day 55, and 1 had vomiting on Day 15. CONCLUSION: Oral UFT/leucovorin and radiation therapy offers patients a viable treatment option for pancreatic cancer. The major known toxicity of diarrhea was tolerable. The MTD was not reached in this study. Our current plan is to expand this into a Phase I/II trial beginning at a UFT dose of 300 mg/m(2) and correlate this with clinical pharmacologic parameters. The potential benefit of long bioavailability and oral delivery of UFT compares favorably with continuous infusion regimens without the added morbidity of a catheter and pump.

Diversity of beta-lactamase activity among clinical isolates of gram-negative bacilli.

Various properties (specific activity, inducibility, substrate profile, and susceptibility to inhibitors) of the beta-lactamase activity present in 39 strains of Enterobacteriaceae and Pseudomonas aeruginosa isolated during a two-month period in the bacteriology laboratory of a large general hospital were investigated. Among the 39 strains there appeared to be at least 16 distinct enzymes. Most enzymes from Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Proteus morganii were active against both penicillins and cephalosporins, whereas those from Proteus vulgaris, Serratia marcescens and Pseudomonas aeruginosa showed activity primarily against cephalosporins. Both types of enzyme were found among strains of Enterobacter. There was a general correlation between amount of enzymic activity and levels of resistance to several beta-lactam antibiotics. Discrepancies between enzymic activity and resistance to several beta-lactam antibiotics. Discrepancies between enzymic activity and resistance may be due to variations in the roles intrinsic mechanisms play in resistance to various antibiotics.

The desmoid tumor. Not a benign disease.

The necessity of aggressive therapy for desmoid tumors has not been clearly established. To evaluate the therapeutic value of adequate resection and radiation therapy, we conducted a retrospective study of 138 patients treated from 1965 through 1984. Univariate analysis revealed five factors predictive of local failure: (1) age between 18 and 30 years, (2) presentation with recurrent disease, (3) partial or limited margin excision, (4) tumor at or close to the microscopic margin of resection, and (5) radiation therapy not administered for gross residual disease. Multivariate analysis identified two of these factors as having independent predictive value for recurrence: (1) presentation with recurrent disease and (2) less-than-adequate margins of resection. The five-year survival probability was 92%, but 11 of the 138 patients died as a consequence of locally uncontrolled tumor. These findings confirm that desmoid tumors are malignant soft-tissue neoplasms that warrant aggressive therapy.

Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by catecholaminergic afferents to the NA-VL.

Control of negative inotropic vagal preganglionic neurons in the dog: synaptic interactions with substance P afferent terminals in the nucleus ambiguus?

Previous research from this laboratory has shown that substance P-immunoreactive (SP) terminals synapse upon negative chronotropic vagal preganglionic neurons (VPNs), but not upon negative dromotropic VPNs, of the ventrolateral nucleus ambiguus (NA-VL). Moreover, SP agonists injected into NA-VL cause bradycardia without decreasing AV conduction. In the current study, we have: (1) defined the electron microscopic characteristics of the SP neurons of NA-VL in dog; and (2) tested the hypothesis that SP nerve terminals synapse upon negative inotropic VPNs of NA-VL, retrogradely labeled from the cranial medial ventricular (CMV) ganglion. Numerous SP terminals and a few SP neurons were observed in the vicinity of retrogradely labeled neurons. SP terminals were observed forming synapses with unlabeled dendrites and with SP dendrites, but never with the retrogradely labeled neurons. Together, these results and earlier findings suggest that SP agonists may be able to induce bradycardia without decreasing AV conduction or ventricular contractility.

Experimental methodologies and preliminary transfer factor data for estimation of dermal exposures to particles.

Developmental efforts and experimental data that focused on quantifying the transfer of particles on a mass basis from indoor surfaces to human skin are described. Methods that utilized a common fluorescein-tagged Arizona Test Dust (ATD) as a possible surrogate for housedust and a uniform surface dust deposition chamber to permit estimation of particle mass transfer for selected dust size fractions were developed. Particle transfers to both wet and dry skin were quantified for contact events with stainless steel, vinyl, and carpeted surfaces that had been pre-loaded with the tagged test dust. To better understand the representativeness of the test dust, a large housedust sample was collected and analyzed for particle size distribution by mass and several metals (Pb, Mn, Cd, Cr, and Ni). The real housedust sample was found to have multimodal size distributions (mg/g) for particle-phase metals. The fluorescein tagging provided surface coatings of 0.11-0.36 ng fluorescein per gram of dust. The predominant surface location of the fluorescein tag would best represent simulated mass transfers for contaminant species coating the surfaces of the particles. The computer-controlled surface deposition chamber provided acceptably uniform surface coatings with known particle loadings on the contact test panels. Significant findings for the dermal transfer factor data were: (a) only about 1/3 of the projected hand surface typically came in contact with the smooth test surfaces during a press; (b) the fraction of particles transferred to the skin decreased as the surface roughness increased, with carpeting transfer coefficients averaging only 1/10 those of stainless steel; (c) hand dampness significantly increased the particle mass transfer; (d) consecutive presses decreased the particle transfer by a factor of 3 as the skin surface became loaded, requiring approximately 100 presses to reach an equilibrium transfer rate; and (e) an increase in metals concentration with decreasing particle size, with levels at 25 microns typically two or more times higher than those at 100 microns--consistent with the earlier finding of Lewis et al. for the same sample for pesticides and polycyclic aromatic hydrocarbons (PAHs).

Tumors of the small intestine.

An analysis of 80 cases of malignant and benign tumors of the small intestine is presented, and major clinical features of various histologic lesions are discussed. Tumors of the small intestine are rare, and the small bowel may have intrinsic protective systems against the development of neoplasms. Gastrointestinal bleeding and symptoms of intermittent obstruction are prominent findings in patients with symptomatic benign tumors, although many benign tumors are incidental findings at operation for an unrelated disease. Benign lesions should be removed by local excision. Virtually all malignant tumors are symptomatic with abdominal pain, nausea and vomiting, anorexia and weight loss, and gastrointestinal bleeding being common findings. Earlier diagnosis is essential if the prognosis for patients with small intestinal malignancies is to be improved. A high degree of suspicion must be aroused with any vague, nonspecific gastrointestinal complaints in patients over 40 years of age. Exploratory celiotomy should be performed in symptomatic patients even though no abnormality may be detected on roentgenographic examination.

Nursing research: quality of life and perceived health in the elderly.

1. Studies have shown that self-perceived health is significantly related to quality of life for older persons. 2. Terminology regarding quality of life and perceived health was found to be inconsistent in the gerontological nursing research reviewed. 3. Outcomes of the research related to quality of life and perceived health fell into three basic categories: predictors found, relationships found, and no relationships found. 4. More experimental research, more replication of research, more research on older males, more use of nursing theory as a framework for research, and more multidisciplinary gerontological research may contribute useful knowledge to the nursing discipline.

Nurses in the African American church.

This study examines the definition and role of the nurse in the African American church. Select members of five churches representing different African American religious denominations were involved in focus groups. A qualitative approach was used to gather the data in unstructured interviews. Historical data and personal accounts of the church nurse were provided by the individuals interviewed. Content analysis was employed to classify data. The interviews described church nursing as a Christian calling to serve others within the church. The role of nursing within the church was found to be unique and include activities which provide comfort and support to the church. The similarities noted between the church nurse and the professional nurse could be significant in developing joint projects to facilitate the implementation of health promotion and health educational programs within the African American church and community.