Evaluation of spinal cord stimulation on the symptoms of anxiety and depression and pain intensity in patients with failed back surgery syndrome.

BACKGROUND: Spinal cord stimulation (SCS) is now established as the primary treatment for failed back surgery syndrome (FBSS). Commonly, patients with chronic pain and FBSS often report symptoms of anxiety and depression resulting from this condition. These factors can modulate and amplify the pain experience, therefore, further challenging treatment success. AIMS: This study examined the efficacy of SCS on alleviating the symptoms of anxiety and depression associated with chronic pain as well as pain intensity in a group of patients with FBSS. METHODS: A convenience sample (n = 26) was selected for participation. Questionnaires [Hospital Anxiety and Depression Scale (HADS) and Brief Pain Inventory Short Form (BPI-SF)] were completed and examined pre and post spinal cord implant. RESULTS: Analysis of the data 1 year following SCS indicates that there was a statistical significant improvement in the symptoms of depression and anxiety reported as well as pain intensity in all participants (p < 0.001). Both anxiety and depression scores on the HADS were significantly lower compared to baseline (p < 0.001). Pain intensity scores decreased by ≥50% from baseline in all participants. Opioid analgesia was discontinued by 90% (n = 8) of participants. CONCLUSION: Whilst it is already recognised that SCS reduces pain in FBSS, this study demonstrated that it also reduced the symptoms of anxiety and depression with an associated reduction in opioid consumption.

Impact of competitive fungi on Trichothecene production by Fusarium graminearum.

Bioassays were used to determine the production of the trichothecene mycotoxin, deoxynivalenol (DON), by two isolates of Fusarium graminearum when grown in association with potentially competitive fungi and an antifungal chemical, 6-pentyl-alpha-pyrone (6PAP). The presence of 6PAP in the culture medium reduced DON production by as much as 80%, but this effect was reduced for the F. graminearum isolate that most efficiently metabolized the added 6PAP. A 6PAP-producing Trichoderma isolate grown in a competition assay system with the F. graminearum isolates was also able to substantially reduce DON production. When Fusarium isolates (F. crookwellense, F. culmorum, F. subglutinans, F. poae, F. equiseti, F. avenaceum, and F. sambucinum), which co-occur with F. graminearum in New Zealand maize plants (Zea mays), were grown in competition assays, the effect on DON production was variable. However, all isolates of F. subglutinans tested were shown to cause reductions in DON production (by 13-76%, mean = 62%). F. subglutinans frequently co-occurs with F. graminearum, but its presence can vary with location and time of the season. When the competitive fungus tested was also a trichothecene producer (e.g., of nivalenol), both toxins were produced in the assay medium. The results indicate that mycotoxin production by F. graminearum can be affected by the presence of particular competitive fungi. These results have implications for an ecological understanding of pathogenicity and of mycotoxin accumulation in plants. Early establishment of F. subglutinans, for example, may act as a biological control mechanism providing a temporary protection against invasion by more commonly toxigenic fusaria such as F. graminearum.

Biotransformation of the Trichoderma metabolite 6-n-pentyl-2H-pyran-2-one by cell suspension cultures of Pinus radiata.

Cell suspension cultures of Pinus radiata metabolize the antifungal Trichoderma secondary metabolite 6-n-pentyl-2H-pyran-2-one (6PAP) (1) via hydroxylation of the pentyl side chain. Examination of the culture medium following dosing studies with 1 revealed that 79-85% of this bioactive compound had been metabolised after 144 h. At that time, 34-40% of the metabolized dose was recovered as a series of monohydroxylated isomers of 1, the principal metabolite being 5-(2-pyron-6-yl)pentan-5-ol (7).

Hypothalamic-pituitary-adrenal axis early-feedback responses are preserved in melancholic depression: a study of sertraline treatment.

Major depression with melancholia is associated with hypercortisolaemia. Loss of the early-phase of negative feedback - acute suppression of ACTH in response to rising cortisol levels - is the subject of conflicting reports in patients with major depression. Using a within-subjects design, six patients with DSM-IIIR melancholic depression received a 60 min infusion of hydrocortisone at 0900 with measurement of ACTH and cortisol before and after 4 weeks of antidepressant treatment. All patients responded clinically. ACTH responses (early feedback) did not differ between test conditions. Baseline cortisol fell significantly following treatment response. This provides further evidence for the preservation of the acute phase of negative feedback, even in the presence of hypercortisolism. Copyright 2000 John Wiley & Sons, Ltd.

Trichoderma/pathogen interactions: measurement of antagonistic chemicals produced at the antagonist/pathogen interface using a tubular bioassay.

A tubular bioassay was used to measure analytically the local production and concentration of the antifungal Trichoderma secondary metabolite 6-n-pentyl-2H-pyran-2-one (6PAP) at the Trichoderma antagonist/pathogen interface. 6PAP levels significantly increased in the presence of the pathogen Botrytis cinerea, typically 300-700%, and were highest near the pathogen source. The level of response for a particular Trichoderma isolate was found to vary with the test organism used. Two products produced by biotransformation of 6PAP by B. cinerea in response to the interaction were also detected.

Specificity of the pyridostigmine/growth hormone challenge in the diagnosis of depression.

Acetylcholine is a neurotransmitter that has been implicated in the pathophysiology of major depression. This is supported by the enhanced growth hormone (GH) release in response to pyridostigmine (PYD) challenge in depressed subjects relative to healthy comparison subjects. The aim of this study is to examine the specificity of the PYD/GH challenge in the diagnosis of depression. Pyridostigmine 120 mg orally, was administered to a total of 116 physically healthy subjects. Growth hormone responses were studied in 38 patients with (DSM-III-R) major depression, 13 subjects with panic disorder, 9 subjects with schizophrenia, 10 recently detoxified alcoholics, and a comparison group of 46 healthy volunteers. Mean delta GH (the difference between basal and maximal GH following PYD) was significantly greater than comparison subjects in patients with major depression. Responses observed in patients with schizophrenia and alcohol dependence syndrome did not differ from the comparison group. Those patients with panic disorder and a high Hamilton depression score had an enhanced delta GH. The sensitivity of the PYD/GH test was 63% for major depression. These results indicate that the PYD/GH test may help distinguish depression from schizophrenia, alcohol-dependence syndrome, or panic disorder with a low Hamilton depression score.

Enhanced growth hormone responses to pyridostigmine challenge in patients with panic disorder.

BACKGROUND: Panic disorder is associated with neuroendocrinological abnormalities, some of which overlap with those seen in major depression. To date, there has been little assessment of the role of cholinergic mechanisms in this disorder. METHOD: Sixteen patients with DSM-III-R panic disorder and an age and gender-matched comparison group were administered 120 mg of the acetylcholinesterase inhibitor pyridostigmine. Growth hormone (GH) responses over a three-hour period were monitored. RESULTS: Mean delta GH, the difference between basal and the maximum pyridostigmine levels, was significantly greater in patients with panic disorder than in the comparison group. CONCLUSIONS: This may reflect increased cholinergic responsivity in panic disorder.

Preservation of hypothalamic-pituitary-adrenal axis fast-feedback responses in depression.

Depression is associated with overactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which may be attributable to defective negative feedback. Fast feedback is the earliest phase of this, and has previously been suggested to be abnormal. A total of 30 physically healthy volunteers, 15 patients with DSM-III-R major depression and an age- and sex-matched control group received a standardized challenge of hydrocortisone (5 micrograms kg-1 min-1) or placebo over a period of 1 h. ACTH1-39 responses to hydrocortisone challenge did not differ significantly between healthy volunteers and patients with major depression. The fast-feedback response to hydrocortisone challenge is preserved in major depression when ACTH is measured directly.

Type II (glucocorticoid) receptors mediate fast-feedback inhibition of the hypothalamic-pituitary-adrenal axis in man.

The hypothalamic-pituitary-adrenal axis is inhibited via negative feedback, which in rats is mediated via type I and II steroid receptors. Although these receptors are present in neural tissue in man, their respective roles have not been systematically examined. Fast-feedback is the first component of negative feedback, occurs within two hours, and is sensitive to the rate of rising cortisol levels. This study examines the role of type I & II steroid receptors in mediating fast-feedback. A within subjects design was used. Subjects were pre-treated with placebo, spironolactone 200mg or RU486 (mifepristone)-type I & II antagonists respectively. This was followed by infusion of either placebo or hydrocortisone. 8 healthy male volunteers were studied on four separate occasions. Plasma cortisol and ACTH were measured by RIA. Significant elevations of morning basal ACTH and Cortisol following RU 486 relative to placebo or spironolactone were observed. ACTH responses to hydrocortisone (i.e. feedback) were not altered by prior administration of spironolactone. In contrast, RU 486 pre-treatment resulted in a significant attenuation of fast-feedback. These results indicate that type II receptors mediate the fast-feedback phase of negative feedback in man.

Commercial assays for serum osteocalcin give clinically discordant results.

Serum samples from 9 healthy controls and from subjects with primary hyperparathyroidism (n = 5), Paget disease (n = 3), pregnancy (n = 5), glucocorticoid therapy (n = 5), postmenopausal osteoporosis (n = 10), and renal failure (n = 10) were used to assess the clinical agreement among eight commercially available assay kits for osteocalcin (OC). These kits differ in their assay configurations (six radioimmunoassays, two immunoradiometric assays), standards (five bovine, three human), and antibodies (six polyclonal, two monoclonal). Individual results were divided by the mean OC of the control subjects for each assay and expressed as percentage deviations. The expected wide variation in absolute OC concentrations between kits was only partially reduced by this transformation. Agreement was equally poor when absolute OC concentrations were compared with the reference ranges quoted by the manufacturers. The discordance was particularly marked in renal failure, presumably because of immunoreactive fragments, and in osteoporosis. Systematic differences could not be attributed to assay format, species source of standard, or antibody specificity. We conclude that results cannot be compared between assays even when normalized against healthy subjects, and that standardization is needed.

Kinetics of technetium-99m-Sestamibi and thallium-201 in a transient ischemic myocardium animal model: insight into the 'redistribution' phenomenon.

This study was designed to determine the redistribution potential for technetium-99m (99mTc)-hexakis-2-methoxy isobutyl isonitrile (99mTc-Sestamibi) as compared to thallium-201 (201Tl) in a transiently ischemic swine heart model. The left anterior descending coronary artery (LAD) was totally occluded for 10 min. One minute prior to the release of the LAD, 99mTc-Sestamibi, 201Tl and a set of 95Nb-radiolabeled microspheres (15 microns) were injected. A second set of 51Cr-radiolabeled microspheres was injected prior to sacrifice in order to document reflow. Animals were sacrificed at different times post-LAD release (ranging from 1 min to 4 h). The left ventricle was sectioned into 0.2- to 0.5-gram pieces for the gamma spectroscopic counting of the 99mTc-Sestamibi, 201Tl and radiolabeled microspheres. Linear regression analysis of radiotracer localization versus microsphere-determined regional myocardial blood flow (rMBF) demonstrates an initial slight filling in of 99mTc-Sestamibi into transiently ischemic zones, with subsequent stable kinetics up to 4 h (i.e., it does not further redistribute). In comparison, the ischemic to normal ratios for 201Tl activity increase progressively in a time-dependent manner. These differences between 99mTc-Sestamibi and 201Tl might be explained on the basis of their blood clearance kinetics and/or their net clearance from normal and ischemic zones of the heart. It is concluded that 99mTc-Sestamibi is a stable and reliable indicator for rMBF over time, and that the lack of normalization of 99mTc-Sestamibi into transient ischemic zones will necessitate two separate injections for differentiation between ischemia and persistent defects.

Detection sensitivity of coronary artery stenosis by 99mTc-sestamibi and 201T1 in canine models of partial and subcritical stenosis.

This study was designed to assess the sensitivity of the monocationic 99mTc-hexakis-2-methoxy, 2-methylpropylisonitrile (99mTc-sestamibi) as compared to 201T1 in the detection of regional myocardial blood flow deficits in dogs with different degrees of stenosis with or without dipyridamole. Regional myocardial distribution of 99mTc-sestamibi and 201Tl was determined in mongrel dogs under different levels of left arterial descending coronary artery (LAD) stenosis (30-45, 60-70 and 100% flow reduction) as monitored with electromagnetic flow probes and radiolabeled microspheres. Both 99mTc-sestamibi and 201Tl distribute in direct proportion to blood flow at all levels of stenosis (r2 = 0.90-0.99). Quantitatively, both tracers underestimate the resting flow stenosis. The regional myocardial distribution for both 99mTc and 201Tl was also determined in subcritically stenosed mongrel dogs. This was produced by placing a balloon cuff around the LAD, infusing dipyridamole to peak hyperemic flow and immediately stenosing the LAD to basal flow. Stenosed to normal zone flow ratios were 0.68 +/- 0.01 compared to 99mTc and 201Tl ratios of 0.73 +/- 0.04 and 0.80 +/- 0.05, respectively. These data suggest that 99mTc is at least as sensitive as 201Tl in the detection of different degrees of critical and subcritical coronary artery stenosis.

Relationship between regional myocardial blood flow and the distribution of 99mTc-sestamibi in the presence of total coronary artery occlusion.

This study was designed to assess the relationship between the distribution of the monocationic 99mTc-hexakis-2-methoxy, 2-methylpropylisonitrile (99mTc-sestamibi) and regional myocardial blood flow (RMBF) in swine. The left anterior descending coronary artery (LAD) was totally occluded and dipyridamole (0.4 mg/kg) was intravenously infused over 4 minutes. 99mTc-sestamibi and 201Tl were coinjected intravenously and a set of microspheres (15 microns) labelled with 113Sn or 55Nb was injected via a left atrial cannula. Animals were put to death at different times after injection of 99mTc-sestamibi/201Tl and the left ventricle was sectioned for gamma spectroscopy. Regression analysis of regional myocardial distribution of 99mTc-sestamibi or 201Tl versus microsphere-determined RMBF demonstrated a linear relationship with flow up to 2.5 ml/min/gm. The myocardial uptake for both 99mTc-sestamibi and 201Tl at higher flow levels was shown not to follow a linear relationship to microsphere-determined RMBF. The first-pass myocardial extraction fractions (%EF) of 99mTc-sestamibi and 201Tl in dogs were 65.5 +/- 2.5% and 82 +/- 3%, respectively (p less than 0.001), at resting flow. At flow levels above the resting flow, a significant decrease in the first-pass extraction fraction for both tracers was shown. At hyperemic flow levels (two to three times the resting flow), the %EF for both tracers are not significantly different. These data provide a basic validation for the utility of 99mTc-sestamibi as a reliable myocardial perfusion imaging agent.

Myocardial cytoprotective efficacy of azapropazone in a canine heart model of regional ischemia and reperfusion.

The present study assessed the efficacy of azapropazone (AZA) in pentobarbital-anesthetized dogs subjected to 120 min of regional ischemia [left anterior descending coronary artery (LAD) ligation] followed by 5 h of reperfusion. Azapropazone was given 30 min prior to LAD occlusion (100 mg/kg i.v.), 35 min prior to LAD release (50 mg/kg, i.v.), and at 2.5 h postreperfusion (50 mg/kg i.v.). Regional myocardial blood flow (RMBF) and area at risk (AAR) were determined with radiolabeled microspheres. The degree and extent of ischemia (anaerobic metabolism) and necrosis were delineated with 14C-deoxy-2-D-glucose (14C-DG) and 111In-antimyosin, respectively, in control (n = 7) and AZA (n = 7)-treated groups. In mild (60-80% normal RMBF) and moderate (30-60% normal RMBF) flow-restricted areas, AZA resulted in a significant decrease in the degree and extent of ischemia (p less than 0.01) with the limitation of infarct size (p less than 0.01). However, AZA did not produce a significant infarct size limitation in the severe flow-restricted area (0-30% of normal RMBF). The effect of AZA is expressed primarily in moderate flow-restricted myocardium with the subsequent infarct size limitation.