[Pulse wave reflection. Determination, extent of influence, analysis and use options].
Explore the source record for details and available documents.
Blood Flow Velocity↗
Biomedical subjects
A Mitchell
Publications and source records attributed to A Mitchell.
The T-allele of the C825T polymorphism is associated with higher arterial stiffness in young healthy males.
Arterial stiffening is the major cause of increasing systolic blood pressure in arterial hypertension. Increased arterial stiffness is one major mechanism responsible for morbidity and mortality in hypertension. A C825T polymorphism was identified in the gene encoding the G-protein beta3 subunit (GNB3), and an association of the T-allele with hypertension was demonstrated in several studies. In order to identify a pathogenetic link between hypertension and arterial stiffness, we compared two indices of arterial stiffness, pulse wave velocity (PWV) and augmentation index, in young, healthy men with and without the 825T-allele under resting conditions. PWV was determined from pressure tracing over carotid and femoral arteries in 99 subjects (CC: n=43; CT&TT: n=56). Augmentation index was derived in 72 subjects (CC: n=30; CT&TT: n=42) by pulse wave analysis using radial applanation tonometry. Carriers of the 825T-allele exhibited a significantly higher PWV compared to subjects with the CC genotype (6.0+/-0.1 m/s (TC&TT) vs 5.7+/-0.1 m/s (CC); P=0.0251). There was also a significant difference (P = 0.0448) in augmentation index between carriers of the T-allele (CT&TT: 3.4+/-2.9%) and controls with the CC -genotype (-5.0+/-4.1 %). There was no difference in any other anthropometric (age, height, weight, body mass index) or haemodynamic (heart rate, peripheral and central blood pressure). In summary, the C825T polymorphism is associated with higher arterial stiffness in young, healthy males. Arterial stiffening may pathogenetically contribute to the development of hypertension in carriers of the T-allele.
Adult↗
Healthy subjects carrying the G protein beta3 subunit 825T-allele exhibit higher uric acid serum levels.
Explore the source record for details and available documents.
Adult↗
What factors influence mental health professionals when deciding whether or not to share a diagnosis of dementia with the person?
This study investigated what influences mental health professionals when deciding whether or not to tell someone with dementia their diagnosis. A qualitative methodology was employed and the data analysed using grounded theory. Currently people with dementia tend not to be told their diagnosis, despite evidence that sharing diagnostic information can improve psychological well-being and adjustment. Why professionals are reluctant to share diagnostic information with people with dementia is unclear, although the literature raises a number of possibilities. Seven professionals were interviewed (two clinical psychologists and five community psychiatric nurses). The main influence on their disclosure practice was uncertainty about whether the person with dementia would want to know the diagnosis, fueled by a fear that to tell them if they did not want to know would cause harm. Professionals also expressed a strong sense of both hopelessness and helplessness when confronted with dementia. This was then projected onto the person with dementia, which in turn led to the professionals adopting an overly protective stance towards them. If professionals are to resolve their sense of uncertainty about what the person with dementia wants, in terms of diagnostic information, services need to develop ways in which the views of people with dementia can be heard and start to influence service provision and policy.
Adaptation, Psychological↗
Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity.
Alzheimer's disease (AD) is a complex neurodegenerative dementing illness. Over the past few years, however, remarkable advances have taken place in understanding both the genetic and molecular biology with the intracellular processing of amyloid and tau and the changes leading to the pathologic formation of extracellular amyloid plaques and the intraneuronal aggregation of hyperphosphorylated tau into neurofibrillary tangles. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in the development of biomarkers. Emerging diagnostic methods that are based on biochemical and imaging biomarkers of disease specific pathology hold the potential to provide effective measures of natural history (marker of disease that is predictive of outcome), biological activity (such as magnitude and frequency of response correlating with drug potency) and markers of surrogate endpoints (single or composite marker that accounts for clinical benefit of the therapy). Markers of biological activity should be also evaluated regarding their value to reflect disease progression, heterogeneity of the clinical population, for early decision making and characterization of new treatments. We focussed on the current status of core analytes which provide reasonable evidence for association with key mechanisms of pathogenesis or neurodegeneration in AD. In addition, feasibility was important, such as availability of a validated assay for the biological measure in question, with properties that included high precision and reliability of measurement, reagents and standards well described. On this basis we reviewed the body of literature that has examined CSF total tau (t-tau) and beta-amyloid 1-42 (Abeta(1-42)), phosphorylated tau (p-tau) and beta-amyloid-antibodies as diagnostic tests for AD versus clinically representative comparison groups. Measurement of t-tau and Abeta(1-42) in the CSF seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. First studies showed that measurement of p-tau proteins significantly improves early and differential diagnosis, as well as disease prediction in subjects at risk for AD and comes closest to fulfilling proposed criteria of a biological marker for AD. However, the nature of the majority of reported findings are still preliminary and retrospective. General issues for biomarkers have to be adequately addressed, such as sensitivity of the method, frequency of assessments, stability of the method, standardization of methods and dynamic range. There is still a partial lack of comparison patient populations that must be addressed in future studies. International dementia networks have been recently established to advance the establishment of core biomarker candidates of AD as potential surrogate endpoints for clinical trials and their clinical use for predictive and diagnostic purposes.
Alzheimer Disease↗
Nitrosative stress induced cytotoxicity in Giardia intestinalis.
AIMS: To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt. METHODS AND RESULTS: Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested. CONCLUSIONS: These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability. SIGNIFICANCE AND IMPACT OF THE STUDY: Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms.
Animals↗
The effect of endocardial defibrillator shocks on basic atrial electrophysiology in man. Is post cardioversion atrial electrical 'remodelling' artefact?
AIMS: To determine the effect of an endocardial DC shock on the basic electrophysiology of the human atrium if delivered in sinus rhythm. METHODS AND RESULTS: A 5J endocardial R wave synchronized DC shock was delivered in 10 patients in stable sinus rhythm during ICD implantation for ventricular arrhythmias. There was no prior history of atrial fibrillation. Monophasic action potential duration (APD) and atrial effective refractory periods (AERP) were evaluated before, 1 min post DC shock, and 15 min post shock. These parameters were assessed at basic cycle lengths and at atrial paced cycle lengths of 600 ms and 400 ms at two right atrial sites; mid lateral right atrial wall (MRLA) and the right atrial appendage (RAA). There were no significant differences in APD 90, AERP or atrial refractory dispersion at any site or drive cycle length before, immediately after or 15 min after shock delivery. CONCLUSIONS: There are no significant changes in basic electrophysiological parameters following a DC shock delivered in sinus rhythm in patients with no prior history of atrial fibrillation. This suggests that atrial electrical remodelling occurs as a result of atrial fibrillation and is unrelated to shock artefact.
Artifacts↗
A new system for regional citrate anticoagulation in continuous venovenous hemodialysis (CVVHD).
BACKGROUND: CVVHD is an established renal replacement therapy in hemodynamically unstable ICU patients. Various methods for regional citrate anticoagulation have been developed to minimize bleeding complications. Metabolic alkalosis, the risk of severe hypocalcemia and need for continuous calcium substitution as well as treatment-associated hypernatremia have limited the success of systems employed so far. We have developed a new technique for regional citrate anticoagulation in CVVHD to overcome these deficiencies and have performed a validation study. METHODS: One hundred and thirty-three filters with an overall treatment duration of 3,324 hours were used in 19 critically ill patients with bleeding complications. We used a calcium-containing dialysate (1.81 mmol/l Ca) to avoid mandatory systemic calcium supplementation. Sodium bicarbonate was added to the dialysate in variable concentrations (13 - 34 mmol/l) to control acid-base status and prevent hypernatremia. The resulting dialysate sodium concentrations were between 121 and 140 mmol/l. Blood flow was set at 75 ml /min. Infusion of a solution containing trisodium citrate and citric acid with an overall citrate concentration of 113 mmol/l was started at 250 ml/h. Primary endpoints were pre- and post-filter ionized calcium (Ca(i)) concentrations, base excess and serum sodium. Filter life was assessed as a secondary end-point. RESULTS: Control of electrolyte balance and azotemia was excellent (prefilter serum Ca(i) 1.06 +/- 0.012 mmol/l (+/- SEM), post-filter Ca(i) 0.23 +/- 0.01 mmol/l, base excess -0.39 +/- 0.4 mmol/l, serum sodium 137 +/- 4 mmol/l, mean serum creatinine 1.8 +/- 0.07 mg/dl). Normal base excess was achieved with a mean dialysate bicarbonate concentration of 26 mmol/l at a mean citrate infusion rate of 266 +/- 4 ml/h. After 48 hours, 25% of filters were still patent, mean filter life was 26 +/- 1.6 hours. No patient developed serious CVVHD-related adverse events. CONCLUSION: The new regional citrate anticoagulation system for CVVHD is safe, feasible and can avoid major complications of previously described methods, especially hypocalcemia, alkalosis and hypernatremia.
Acute Kidney Injury↗
Domestic ruminants as models for the elucidation of the mechanisms controlling ovarian follicle development in humans.
It is necessary to understand the basic physiology underlying the complex process of folliculogenesis to address common causes of infertility and to devise innovative strategies to increase the efficiency of assisted reproduction technologies. Availability of suitable ovarian tissue is a major constraint to research in this area in humans, and monovulatory domestic ruminants represent a physiologically relevant model to elucidate basic mechanisms before more focused clinical investigations. This paper reviews the development of several whole animal and cell culture models in ruminants that have allowed basic investigations into the endocrine and local mechanisms regulating preantral and antral follicle development in monovulatory species. Studies on preantral follicle development using the ovarian autograft model have shown, contrary to accepted dogma, that FSH may mediate the rate at which preantral follicles grow and have provided evidence to support the existence of local regulatory feedback mechanisms that influence the rate of primordial follicle initiation and preantral follicle development. Studies on the endocrine control of antral follicle development using the GnRH-antagonist model have shown that a pulsatile mode of LH delivery is not a requirement for normal patterns of follicle development and ovarian hormone secretion. Studies on the local control of somatic cell differentiation using physiological cell culture models have highlighted the essential relationship between somatic cell communication and expression of differentiative markers. We conclude that the domestic ruminant represents a valuable model system for the elucidation of the endocrine and local mechanisms controlling both early and terminal stages of follicle development in monovulatory species. The results of these investigations have direct strategic relevance within clinical medicine.
Animals↗
Hormonal control of folliculogenesis: the key to successful reproduction.
Explore the source record for details and available documents.
Animals↗
Cognitive-behavioural therapy for schizophrenia.
Explore the source record for details and available documents.
Cognitive Behavioral Therapy↗
[Transsphenoidal hypophysectomy of a patient with an ACTH-producing pituitary adenoma and an "empty sella" after pretreatment with etomidate].
HISTORY AND ADMISSION FINDINGS: A seventy-year-old woman was admitted to our hospital under suspicion of an adrenal Cushings's syndrome. Initial laboratory values showed elevated cortisol (834 nmol/l; normal: 180-640) which could not be suppressed after administration of 2 mg dexamethasone (632 nmol/l). Computed tomography of the abdomen showed a 19 x 34 mm mass in the region of the left adrenal gland. INVESTIGATIONS: ACTH levels were normal (42 ng/ml; 17-52). Serum cortisol remained high at 1021 nmol/l after administration of 8 mg dexamethasone. Four more doses of 2 mg dexamethasone were applied on 3 consecutive days, leading to a mild suppression of serum cortisol to 705 nmol/l, with urine cortisol levels dropping from 1915 to 101 nmol/l/24 h. The CRH-test produced a rise of serum cortisol from 895 to 1475 nmol, with ACTH rising from 42 to 68 pg/ml, a laboratory constellation consistent with the diagnosis of centrally located Cushing's syndrome (Cushing's disease). MRI failed to show an adenoma of the pituitary gland so that sinus petrosus sampling was done to confirm the diagnosis (ACTH central/peripheral 7:1; normal range < 2:1). TREATMENT AND COURSE: Serum cortisol rose to 1070 nmol/l and the patient developed pneumonia and contracted tinea. Prior to surgery we lowered the excessive cortisol levels with etomidate and successfully treated the pneumonia with antibiotics. Postoperatively clinical symptoms of Cushing's syndrome disappeared. The patient now presented with total insufficiency of the anterior pituitary. CONCLUSION: Exact hormone testing that may involve sinus petrosus sampling is necessary in diagnosing Cushing's syndrome. Even if radiological procedures cannot show an adenoma of the pituitary, transsphenoidal resection should be considered. Etomidate can lower excessive cortisol levels in seriously ill patients.
Adenoma↗
Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?
BACKGROUND: To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. METHODS: In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. RESULTS: Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. CONCLUSIONS: Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo.
Adrenergic alpha-1 Receptor Antagonists↗
Progesterone receptor and dopamine receptors are required in Delta 9-tetrahydrocannabinol modulation of sexual receptivity in female rats.
Ovarian steroids, estrogen and progesterone, influence the sensitivity of certain neural processes to cannabinoid treatment by modulation of brain dopaminergic activity. We examined the effects of the active ingredient of cannabis, Delta(9)-tetrahydrocannabinol (THC), on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity. Our results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D(1) receptors. To test further the idea that progesterone receptors (PR) and/or dopamine receptors (D(1)R) in the hypothalamus are required for THC-facilitated sexual behavior in rodents, antisense and sense oligonucleotides to PR and D(1)R were administered intracerebroventricularly (ICV) into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone- and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D(1)R. Antagonists to cannabinoid receptor-1 subtype (CB(1)), but not to cannabinoid receptor-2 subtype (CB(2)) inhibited progesterone- and dopamine-facilitated sexual receptivity in female rats. Our studies indicate that THC acts on the CB(1) cannabinoid receptor to initiate a signal transduction response that requires both membrane dopamine and intracellular progesterone receptors for effective induction of sexual behavior.
Animals↗
Treatment with parathyroid peptides and estrogen replacement for severe postmenopausal vertebral osteoporosis: prediction of long-term responses in spine and femur.
Fifteen women with severe vertebral osteoporosis were treated with daily parathyroid peptide (hPTH) plus hormone-replacement co-therapy (HRT) for 1 year. Eight other patients were randomized to HRT alone. Co-therapy with hPTH and HRT resulted in an impressive mean treatment response at the spine (dual-energy X-ray absorptiometry DXA) 15% above baseline; P < 0.015 compared with the HRT group) at 2 years, while at the proximal femur and radius there were smaller increases. hPTH co-therapy led to a significantly positive metabolic calcium balance at 1 year (by 2.13 mmol Ca/day, equivalent to a 5% annual increment in total body calcium; P = 0.015). The magnitude of the lumbar spine DXA response at 2 years depended statistically on the increase in bone formation rate, measured with 85Sr (r2 adjusted 0.48; P < 0.005) and patients with a large spine DXA response had larger calcium balance improvements (P < 0.03). Plasma osteocalcin changes tracked closely with increases in bone formation rate (r2 = 0.87). In seven patients treated throughout with HRT alone, and in eight hPTH-treated patients (three of whom switched to bisphosphonate therapy at year 4). DXA spine changes seen in years 3-5 were minimal, with no evidence of a statistically significant difference between groups. It is concluded that hPTH or comparable PTH receptor activators remain the most promising anabolic treatment for osteoporosis currently under clinical evaluation and a 6- or 12-month measurement of bone formation or a marker predicts the 2-5 year bone density outcome. Post-hPTH treatment, loss of bone appeared preventable with anti-resorptive therapy.
Bone Density↗
Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension.
OBJECTIVES: This study was designed to establish a patient-controlled, ambulatory norepinephrine treatment of refractory orthostatic hypotension due to primary autonomic failure. BACKGROUND: Autonomic dysfunction leads to disabling postural hypotension. Particularly in primary autonomic dysfunction, repeated syncope and immobilization can be the result. Medical treatment of orthostatic hypotension often fails in advanced cases. METHODS: Ambulatory, patient-controlled norepinephrine therapy was initiated in six patients with orthostatic hypotension due to primary autonomic failure that had been refractory to conventional treatment. Before this therapy, three patients were bedridden; one was immobilized in a wheelchair. All had recurrent syncope and tolerated upright tilt-table testing for less than 15 min despite extensive medical treatment. For ambulatory treatment, a port-a-cath system was implanted and, using a CADD ambulatory infusion pump, norepinephrine was infused in individually adjusted dosages. RESULTS: Norepinephrine infusion therapy enabled all patients to sit, stay and walk around for more than 45 min. One patient died after a five-year treatment period, another after nine months because of nonhemorrhagic brain stem infarctions, both in the absence of norepinephrine treatment. The remaining four patients are still mobile after a period of 19, 10, 9 and 7 months, respectively. None of them has suffered complications due to arterial hypo- or hypertension, and there has been no infection of the infusion system. CONCLUSIONS: In these selected patients with refractory orthostatic hypotension due to primary autonomic dysfunction, ambulatory norepinephrine infusion therapy has proved to be a promising new therapeutic option. Further long-term studies including more patients are necessary to assess additional indications, reliability and safety of this new method.
Aged↗