PubMed Health⌕ Search

Biomedical subjects

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↗

Emotional dysfunction in schizophrenia spectrum psychosis: the role of illness perceptions.

BACKGROUND: Assessing illness perceptions has been useful in a range of medical disorders. This study of people with a recent relapse of their psychosis examines the relationship between illness perception, their emotional responses and their attitudes to medication. METHOD: One hundred patients diagnosed with a non-affective psychotic disorder were assessed within 3 months of relapse. Measures included insight, self-reported illness perceptions, medication adherence, depression, self-esteem and anxiety. RESULTS: Illness perceptions about psychosis explained 46, 36 and 34% of the variance in depression, anxiety and self-esteem respectively. However, self-reported medication adherence was more strongly associated with a measure of insight. CONCLUSIONS: Negative illness perceptions in psychosis are clearly related to depression, anxiety and self-esteem. These in turn have been linked to symptom maintenance and recurrence. Clinical interventions that foster appraisals of recovery rather than of chronicity and severity may therefore improve emotional well-being in people with psychosis. It might be better to address adherence to medication through direct attempts at helping them understand their need for treatment.

Adult↗

Understanding suicidal ideation in psychosis: findings from the Psychological Prevention of Relapse in Psychosis (PRP) trial.

OBJECTIVE: To examine the clinically important phenomenon of suicidal ideation in psychosis in relation to affective processes and the multidimensional nature of hallucinations and delusions. METHOD: In a cross-sectional study of 290 individuals with psychosis, the associations between level of suicidal ideation, affective processes, positive symptoms, clinical and demographic variables were examined. RESULTS: Forty-one per cent of participants expressed current suicidal ideation. Suicidal ideation was associated with depressed mood, anxiety, low self-esteem, negative illness perceptions, negative evaluative beliefs about the self and others and daily alcohol consumption. Frequency of auditory hallucinations and preoccupation with delusions were not associated with suicidal ideation; however, positive symptom distress did relate to suicidal thoughts. CONCLUSION: Affective dysfunction, including distress in response to hallucinations and delusions, was a key factor associated with suicidal ideation in individuals with psychotic relapse. Suicidal ideation in psychosis appears to be an understandable, mood-driven process, rather than being of irrational or 'psychotic' origin.

Adult↗

Influence of carer expressed emotion and affect on relapse in non-affective psychosis.

BACKGROUND: High expressed emotion in carers predicts relapse in psychosis, but it is not known why this is so. In our cognitive model of psychosis, we postulated that the effect is mediated through affective changes. AIMS: To investigate the relationships between carer expressed emotion, patients' symptoms and carer characteristics during a recent relapse of psychosis. METHOD: A total of 86 patients and carers were investigated in a cross-sectional design. RESULTS: Patients whose carers showed high expressed emotion had significantly higher levels of anxiety and depression, but not more psychotic symptoms or lower self-esteem. Linear regression showed that carers'critical comments predicted anxiety in patients. Critical comments were related to low carer self-esteem and avoidant coping strategies. Low carer self-esteem was also related to carer depression, stress and carer 'burden', and to low patient self-esteem. CONCLUSIONS: Our hypothesis was partially supported. Carer criticism was associated with patient anxiety, low carer self-esteem and poor carer coping strategies. Family interventions should focus on improving these after a relapse of symptoms of psychosis.

Adaptation, Psychological↗

The influence of dispersant concentration on the pore morphology of hydroxyapatite ceramics for bone tissue engineering.

There is a clinical need for synthetic scaffolds that will promote bone regeneration. Important factors include obtaining an optimal porosity and size of interconnecting windows whilst maintaining scaffold mechanical strength, enabling complete penetration of cells and nutrients throughout the scaffold, preventing the formation of necrotic tissue in the centre of the scaffold. To address this we investigated varying slip deflocculation in order to control the resulting porosity, pore size and interconnecting window size whilst maintaining mechanical strength. Hydroxyapatite (HA) porous ceramics were prepared using a modified slip casting process. Rheological measurements of the HA slips were used to identify deflocculation conditions which resulted in changes in the cell and window sizes of the resulting ceramics. Sintered ceramics were characterised by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Pore and window size distribution was determined by SEM. XRD analysis confirmed that the crystal structure remained HA after the sintering process. SEM showed that HA porous ceramics presented a highly interconnected porous network with average pore sizes ranging from 391+/-39 to 495+/-25 microm. The average window size varied from 73+/-5 to 135+/-7 microm. Pore diameters obtained were controllable in the range 200-500 microm. Window sizes were in the range 30-250 microm. The use of dispersant concentration allows pore and window size to be modified whilst maintaining control over porosity demonstrated by a porosity of 85% for seven different dispersant concentrations. The advantage of this approach allows the correlation between the rheological conditions of the slip and the resultant sintered ceramic properties. In particular, optimising the ceramic strength by controlling the agglomeration during the casting process.

Bone Substitutes↗

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model.

Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of men. Specific cohorts of patients with severe vascular or neurogenic basis to their ED, such as diabetic men or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of nitric oxide (NO) may be enhanced through delivery of adequate concentrations of free oxygen radical scavenger molecules such as vitamin E. Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a PDE5 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) diabetic rats were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II--vitamin E 20 IU/day, group III--sildenafil 5 mg/kg/day and group IV--vitamin E 20 IU/day plus sildenafil 5 mg/kg/day, by oral gavage daily for 3 weeks. Erectile function was assessed as a rise in intracavernous pressure following cavernous nerve electrostimulation. Penile tissue was harvested to determine the changes in tissue morphology including neuronal nitric oxide synthase, smooth muscle alpha-actin and endothelial cell integrity. PDE5 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined vitamin E plus sildenafil treatment. Immunohistochemical staining showed increases of neuronal nitric oxide synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of PDE5 protein between the groups. However, higher PDE5 activity was measured in the sildenafil group and lower activity of PDE5 was recorded in the cohort receiving vitamin E with sildenafil. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in a meaningful way in this animal model of diabetes. This study indicates a potential means of salvaging erectile function among patients who are refractory to sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗

CBT for psychosis.

Explore the source record for details and available documents.

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↗