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D Freeman

Publications and source records attributed to D Freeman.

At least 19 recordsLinked to original sources

Addressing the dual-use of antifungals and fungal antimicrobial resistance (fAMR) through a One Health approach.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

Journal Article↗

CBT for psychosis.

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Cognitive Behavioral Therapy↗

Gender and health services use for a mental health problem.

This study addresses whether the predictors of seeking help for a mental health problem differ by gender. An adaptation of Andersen's Socio-Behavioral Model is used to identify factors associated with seeking care for a mental health problem. Data are derived from two waves of a community survey undertaken in 1992-1993 and in 1993-1994 among a probability sample of adults (18-69 years), residing in poor areas of Puerto Rico. Paired data was used from those individuals who responded to both waves of the survey for a total of 3221 community respondents. Responses from wave 1 were used to predict mental health service use in wave 2. The dependent variable is any use of outpatient mental health services in the year preceding the second interview. Logistic regression was used to model the effects of the independent variables on use. Males and females were found to use mental health services in nearly equal proportions. Gender did not have a main effect on use when other covariates were controlled. Significant interactions with gender were found for several predictors of use. The largest intervention effects were encountered in our need for care indicators. Having a definite need for mental health care and poor self-rated mental health had a larger effect on predicting use of services for men than they do for women. It is concluded that strategies designed to improve access to mental health services for minority disadvantaged populations ought to take into account gender differences in the predictors of use. Studies addressing factors influencing health services utilization for a mental health problem should consider stratifying their sample by gender. Future research should establish whether or not these findings are sustained with other population groups.

Adolescent↗

Persecutory delusions: developing the understanding of belief maintenance and emotional distress.

BACKGROUND: The objective of the study was to develop the cognitive understanding of persecutory delusions. It was hypothesized that safety behaviours contribute to the persistence of persecutory delusions by preventing disconfirmation. It was further hypothesized that emotional distress is associated with aspects of the content of delusions. An investigation was designed to establish whether individuals with persecutory delusions use safety behaviours, and to test predicted associations between delusion content and emotional distress. METHOD: A cross-sectional investigation was conducted on 25 individuals with persecutory delusions. A detailed assessment was made of the presence of safety behaviours, the content of delusions and emotional distress. RESULTS: All participants had used at least one safety behaviour in the last month, most typically avoidance. Higher levels of anxiety were associated with greater use of safety behaviours. New data were obtained on the content of persecutory delusions. Aspects of the content of the delusions were associated with levels of depression, self-esteem, anxiety and delusional distress. CONCLUSIONS: Individuals with persecutory delusions use safety behaviours. The findings may develop the understanding of delusion persistence, acting upon delusions and the negative symptoms of schizophrenia. There are implications for cognitive interventions for psychosis. Support was also found for the hypothesis that emotional distress is linked to the content of delusional beliefs; it is speculated that prior emotional distress influences the content of delusions, and that delusion content in turn influences levels of emotional distress.

Adult↗

Bi-modality (chemo-radiation) versus tri-modality (chemo-radiation followed by surgery) treatment for carcinoma of the esophagus.

The purpose of the study was to investigate the difference in overall survival in patients with localized carcinoma of esophagus treated using chemo-radiation (bi-modality, BM) or chemo-radiation followed by surgery (tri-modality, TM). From 1981 to 1999, 65 patients were identified who had localized carcinoma of the esophagus treated with either concurrent chemo-radiation (BM, n=22) or concurrent chemo-radiation followed by surgery (TM, n=43) at the University of Texas Medical Branch at Galveston. All 65 patients received concurrent chemotherapy and external beam radiation. Radiation was delivered by linear accelerators (greater-than-or-equal 6 MV), except in one patient who had part of his treatment given by a Co-60 machine. Chemotherapy consisted of 5-fluorouracil and cisplatin plus minus vinblastine under different regimens. Median follow-up time was 10 months (range=1-195 months) for all patients. Of the 14 patients still alive, the median follow-up time was 32 months (range=2-192 months). No difference in overall survival was detected between the two treatment groups, BM vs. TM (P=0.394) despite a selection bias favoring the TM group. Five-year survival rates of the BM and TM groups were 17% and 18%, respectively; 10-year survival rates were 17% and 12%, respectively. The presence of significant past medical history (P=0.017) and a complete pathologic response in the TM group (P < 0.001) were significant independent predictors of survival. We did not find any difference in survival between chemo-radiation or chemo-radiation followed by surgery in patients with localized carcinoma of the esophagus. Use of biologic markers and functional imaging should be explored in order to segregate patients with different tumor biology for treatment using different treatment strategies.

Aged↗

Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases.

UNLABELLED: Nitrous oxide increases total homocysteine (tHcy) plasma levels, which are associated with an increase in perioperative myocardial ischemia. We designed this study to determine whether oral B vitamins, which are cofactors in homocysteine metabolism, can prevent nitrous oxide anesthesia-induced tHcy increases in patients undergoing elective surgery scheduled to last longer than 3 h. Fifty-three patients presenting for elective revision knee or hip arthroplasty received in random, double-blinded fashion oral vitamin B complex (folate 2.5 mg, B(6) 25 mg, and B(12) 500 microg) or placebo daily for 1 wk before surgery. Anesthesia was induced with propofol and maintained with an opioid, isoflurane, and nitrous oxide/oxygen (inspired nitrous oxide >50%). Blood samples for measurement of tHcy concentration were obtained at study enrollment, before induction, on arrival in the postanesthesia care unit, and on Day 5. Fourteen patients had their surgery rescheduled after taking their vitamins and were removed from the study. The Placebo group had a mean increase in tHcy concentration from baseline of 15% +/- 31% compared with the Vitamin group, which had an initial decrease of 9.1% +/- 11% (P = 0.035). This was maintained throughout the 5-day study period. The use of an oral B vitamin complex prevented the increase in postoperative tHcy by nitrous oxide. IMPLICATIONS: The use of nitrous oxide anesthesia increases postoperative homocysteine concentrations and associated myocardial ischemia. This study indicates that a 1-wk course of oral B vitamins can prevent the increase in homocysteine from nitrous oxide, and, by implication, myocardial ischemia as well.

Administration, Oral↗

Solvatochromic effects in the electronic absorption and nuclear magnetic resonance spectra of hypericin in organic solvents and in lipid bilayers.

The natural product hypericin was tested in recent years as a biological photosensitizer with a potential for viral and cellular photodamage. We thus studied extensively its spectroscopy and membrane partitioning. Absorption, fluorescence excitation and emission spectra of the sodium salt (HyNa) were measured in 36 protic and aprotic, polar and apolar, solvents. Electronic transition bands as well as vibrational progressions were identified. Aggregation in some nonpolar solvents and protonation in organic acids were demonstrated. Modeling solvatochromism was done by Lippert equation, by the ET(30) parameter and by the Taft multiparameter approach. In all cases, separation into protic and aprotic solvents gave much better fits to the models. 13C chemical shift data could also be correlated with solvent polarity. They correlated best with Lippert's delta f polarity measure, but tended to fall into two distinct solvent groups--each along different lines--corresponding to protic and aprotic media, respectively. This interesting phenomenon suggests that in the case of the charged and slightly water soluble HyNa, two mechanisms of solvation are involved, each resulting in its own line equation. In aprotic media, dipole-dipole interaction is the predominant solvation mechanism. In protic solvents, the most effective means of solvation is likely to be hydrogen bonding. When intercalated into the liposomal phospholipid bilayer, HyNa is oriented at an angle to the interface, thus experiencing a gradient of solvent polarities: a highly polar environment (similar to methanol) for C-2/5, suggesting that they lie not far from the interface; a moderately polar environment (similar to that of n-propanol) for C-6a/14a, which are somewhat deeper within the bilayer; and a more lipophilic environment (akin to n-hexanol) for C-10/11. The fluorescence excitation peak in liposomes also correlates with an aprotic medium of relatively high polarity, as might be excepted from a molecule in a shallow position in the bilayer.

Anthracenes↗

Hypericin derivatives: substituent effects on radical-anion formation.

The electron-transfer properties of the hypericin derivatives, dibromo-, hexaacetyl-, hexamethyl- and desmethylhypericin, were studied. Cyclovoltammetric measurements revealed that dibromo- and desmethylhypericin have almost the same redox potentials as the parent hypericin. Substitution of the hydroxyl groups by acetoxy leads to less negative E1/2 values, whereas methoxy substitution induces more negative values. Electron paramagnetic resonance (EPR)/electron nuclear double resonance/general TRIPLE spectroscopy and quantum mechanical calculations were used to establish the structure of the one-electron reduced stages of hypericin derivatives. Proton loss in the bay region, already demonstrated for hypericin, was also found for dibromo- and desmethylhypericin. The spin and charge of the radical ions are predominately confined to the central biphenoquinone moiety of the hypericin skeleton. Generation of the radical ions by in situ electrolysis indicates that the redox potentials of hypericin, dibromo- and desmethylhypericin, containing hydroxyls at the 1, 3, 4, 6, 8 and 13 positions, largely depend on the solvent. With phosphate-buffered saline (pH 7.4)/dimethylsulfoxide (DMSO) as the solvent the EPR spectra of the corresponding radical ions appear at markedly lower potentials than in pure DMSO and N,N'-dimethylformamide. However, this effect is not observable for hexaacetyl- and hexamethyl-hypericin-lacking hydroxyl groups. In all cases the EPR data and calculations revealed the presence of 7,14 tautomers.

Anions↗

The structure of hypericin in solution. Searching for hypericin's 1,6 tautomer.

Hypericin in organic solvents displays two types of electronic spectra: one type which shows a distinct solvatochromic effect, the stable form, and the other, the unstable form, which lacks this property. The latter type is formed in dry nonprotic solvents (e.g. tetrahydrofuran, EtOAc) and can be converted to the stable form on addition of protic solvents. In order to establish the tautomeric structure of the unstable form we applied conventional nuclear magnetic resonance techniques as well as two-dimensional gradient-enhanced heteronuclear multiple-quantum correlation, gradient-enhanced ROESY and one-dimensional nuclear Overhauser effect difference experiments. All these techniques pointed to the fact that the unstable form has the 7,14-diketo tautomeric structure, like the stable form, and not the 1,6-diketo structure. Electronic spectroscopy indicated that the unstable form has acidic properties and therefore possesses two free OH groups at C3 and C4 at the bay region of the molecule.

Anthracenes↗

Sonographic examination of lateral epicondylitis.

OBJECTIVE: The purpose of this study was to describe the sonographic appearance of the common extensor origin in cadavers and asymptomatic volunteers, and to relate this appearance to the findings in patients with lateral epicondylitis. SUBJECTS AND METHODS: Seventy-two elbows in 71 patients with lateral epicondylitis were examined on sonography. Most of the patients (60/71) gave a history of repetitive microtrauma. The injuries were evaluated with respect to location and severity. Focal areas of degeneration, discrete cleavage tears, and involvement of the lateral collateral ligament were identified. Calcification and bony changes were noted. The appearance of the normal common extensor tendon was described, and cadaveric specimens were dissected. Twenty-one patients subsequently underwent surgery. RESULTS: The normal common extensor origin is composed of longitudinal fibrils bound closely with the extensor carpi radialis brevis constituting most of the deep fibers, with the extensor digitorum making up the superficial part. The lateral collateral ligament can be identified as a discrete and separate band. The most common appearance of lateral epicondylitis is a focal hypoechoic area in the deep part of the tendon (46/72). These focal areas were identified at surgery and corresponded histologically to collagen degeneration with fibroblastic proliferation. Often discrete cleavage planes traversing the tendon were manifest as partial (18/72) and complete (2/72) tears. The lateral collateral ligament was involved in eight of 72 elbows. CONCLUSION: Sonography of the common extensor origin can be used to confirm lateral epicondylitis in patients with lateral elbow pain and provide information about the severity of the disease.

Adult↗

Liposome binding constants and singlet oxygen quantum yields of hypericin, tetrahydroxy helianthrone and their derivatives: studies in organic solutions and in liposomes.

The spectroscopy and photophysics of several hypericin and helianthrone derivatives were studied in methanol and when bound to liposomes. The singlet oxygen quantum yields (phi(delta)) were measured indirectly relative to Rose Bengal and hematoporphyrin IX, employing 9,10-dimethylanthracene as a singlet oxygen trap. Hypericin was found to have a phi(delta) of 0.39+/-0.01 in methanol, and 0.35+/-0.05 in lecithin vesicles, in agreement with literature values. A heavy atom effect was evident upon bromination, resulting in phi(delta) for tetrabromohypericin of 0.72+/-0.02, presumably due to enhanced intersystem crossing. Elimination of the anionic hydroxyls by methylation also enhanced phi(delta) to 0.81+/-0.01. Conversely, addition of anionic sulfate groups drastically reduced phi(delta) resulting in phi(delta)'s of 0.12+/-0.01, 0.052+/-0.003 and 0.40+/-0.01 for hypericin disulfonate, hypericin tetrasulfonate and hexamethyl hypericin tetrasulfonate, respectively. The non-sulfonated helianthrones exhibited low phi(delta)'s in solution. The liposome binding constants, Kb, were measured using a spectroscopic assay. Except for hexamethyl hypericin, all non-sulfonated compounds bound well with Kb's ranging from 15.5+/-0.1 to 48.7+/-3.9 (mg/ml)(-1). None of the tetrasulfonated compounds bound, however the hypericin disulfonate had a Kb of 4.1+/-0.2 (mg/ml)(-1). The phi(delta)'s of the compounds capable of binding were measured and, in the case of the hypericin derivatives, were found not to vary dramatically from those in the free state. Liposome-bound helianthrone and dimethyl tetrahydroxy helianthrone both exhibited high phi(delta)'s, i.e. >0.5. The variations in binding constant and sensitization efficiencies are explained in conjunction with the molecular structure. The relevance of the above data to photodynamic therapy is briefly discussed.

Anthracenes↗

An examination of hypervigilance for external threat in individuals with generalized anxiety disorder and individuals with persecutory delusions using visual scan paths.

One account of generalized anxiety disorder (GAD) is that it results from hypervigilance, manifest as excessive scanning of the external environment and preferential attention to threat. However, for individuals with GAD, there has been no direct study of scanning, and evidence for preferential attention to threat has only been found for threat-words. We therefore devised a new measure of hypervigilance. Visual scan paths were recorded of individuals with GAD (N = 12) and people without a psychiatric illness (N = 12) viewing complex pictures that varied in threat content. People with persecutory beliefs (N = 11) also participated in the study to test the hypothesis that anxiety, via such hypervigilant cognitive processes, may contribute to the maintenance of delusions. Compared with the control group, the anxious individuals were not found either to scan excessively for or to look at threat. The anxiety group was therefore not hypervigilant for external threat, which is inconsistent with the hypervigilance model. As a consequence, the hypothesis that anxiety maintains delusions was not tested. However, additional support was found for the hypothesis that people with delusions form rapid judgements on the basis of less data-gathering than control groups who are either anxious or have no psychiatric illness.

Adult↗

Nitrous oxide-induced increased homocysteine concentrations are associated with increased postoperative myocardial ischemia in patients undergoing carotid endarterectomy.

UNLABELLED: Nitrous oxide anesthesia causes increased postoperative plasma homocysteine levels. Acute increases in plasma homocysteine are associated with impaired endothelial function and procoagulant effects. This nitrous oxide-induced plasma homocysteine increase may therefore affect the risk of perioperative cardiovascular events. This prospective, randomized study was therefore designed to evaluate the effect of nitrous oxide anesthesia and postoperative plasma homocysteine levels on myocardial ischemia in patients undergoing carotid endarterectomy. After institutional review board approval and written informed consent, 90 ASA Class I-III patients presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Prior to induction, on arrival in the postanesthesia care unit, and after 48 h, blood samples were obtained for homocysteine analysis. Three hours prior to induction and for 48 h postoperatively patients were monitored by a three-channel, seven-lead Holter monitor. Postoperatively in the postanesthesia care unit and at 48 h the nitrous oxide group had increased mean plasma homocysteine concentrations of 15.5 +/- 5.9 and 18.8 +/- 14.7 when compared with the nonnitrous group of 11.4 +/- 5.2 and 11.3 +/- 4.0 micromol/L, P: < 0.001. The nitrous oxide group had an increased incidence of ischemia (46% vs. 25%, P: < 0.05), significantly more ischemia (63 +/- 71 vs. 40 +/- 68 min, P: < 0.05), had more ischemic events (82 vs. 53, P: < 0.02), and had more ischemic events lasting 30 min (23 vs. 14, P: < 0.05) than the nonnitrous group. This study reconfirmed that intraoperative nitrous oxide is associated with postoperative increases in plasma homocysteine concentration. This was associated with an increase in postoperative myocardial ischemia. IMPLICATIONS: Use of nitrous oxide during carotid artery surgery induces increases in postoperative plasma homocysteine concentration and is associated with increases in postoperative myocardial ischemia.

Aged↗

Comments on the content of persecutory delusions: does the definition need clarification?

Diagnostic criteria for subtypes of delusional beliefs based upon content have rarely been the subject of comment. In this article, several influential accounts of persecutory delusions are reviewed; differences and difficulties are noted, and their potential effect on cognitive psychological investigations discussed. One method of ensuring that researchers study similar phenomena is to use a more detailed definition than currently available, and therefore a new set of criteria is offered. Finally, related methodological problems in this emerging research area are highlighted. The issues discussed may stimulate further research on the content of delusional beliefs.

Delusions↗

Validation of an enzyme immunoassay for the determination of total homocysteine in plasma.

In recent years, the determination of homocysteine (Hcy) has become increasingly important, since high levels of Hcy in plasma or serum represent an independent risk factor for occlusive vascular diseases. Nowadays, clinical laboratories use several analytical techniques to measure Hcy, of which high-performance liquid chromatography (HPLC) is the most popular. Recently, assays for Hcy quantification based on enzyme immunoassays (EIA) have become commercially available. Our group carried out the validation of the Axis method and compared results with those obtained by an established HPLC assay. Intra- and inter-assay coefficients of variation were < or = 8.5%. Compared with HPLC, linear regression analysis showed r=0.984, slope=0.952, intercept = 1.24 /mol/l; Bland-Altman procedure, the mean of the difference EIA-HPLC results = 0.5 micromol/l. Our results suggest that Hcy determinations by both methods are equivalent, and that the Axis assay provides reproducible and reliable data.

Homocysteine↗