The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors

BACKGROUND: Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors. Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration. This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors. METHODS: Patients (n = 20) were recruited from a prospective, randomized double-blind study on the hemodynamic effects of hydrocortisone during septic shock. Eleven patients had received placebo and nine stress doses of hydrocortisone. Posttraumatic stress disorder was diagnosed 31 months (median) after intensive care unit discharge using SCID-IV (DSM-IV-criteria). Furthermore, the number of categories of traumatic memory from ICU treatment was determined in both groups at that time. RESULTS: Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder, compared with seven of 11 patients in the placebo group (p =.02). There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups. CONCLUSIONS: The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors, which seems to be independent of the number of categories of traumatic memory.     

Studies on blood coagulation activity during storage of red cell products intended for transfusion

Preservation of red blood cells in special media, such as saline-adenine-glucose-mannitol (SAGM) solution involves storage at a citrate and plasma protein concentration much lower than found in normal CPD or CPD-adenine plasma. In the present study, the effects on the coagulation and other connected enzymatic systems in SAGM medium have been investigated. Significantly higher levels of fibrinopeptide A (FPA) and plasma kallikrein activity were observed in the SAGM medium compared to CPD plasma, indicating an increased enzymatic activation in the SAGM medium. For this reason storage of red cells in SAGM solution, supplemented with citrate, was tested and compared with storage in SAGM and CPD plasma. The results demonstrate a positive effect of citrate as an added ingredient in the SAGM solution. Significantly lower levels of primarily FPA but also decreased activities of plasma kallikrein and general proteolysis were noticed. The decreased citrate concentration in Red Blood Cells stored in SAGM protein poor medium must be considered to have a destabilizing influence on the coagulation and on other connected enzymatic systems.     

Studies of fibrinolytic and coagulation factors during open heart surgery. II. Postoperative bleeding tendency and changes in the coagulation system.

In 9 patients with and without signs of preoperative increased turnover of coagulation factors were examined during and after open heart surgery by ECC the following coagulation parameters: thrombelastogram, partial thromboplastin time, thrombin time, platelets, antithrombin-III-activity and the separate plasmic coagulation factors (II, V, VII, VIII, IX, X). During ECC a qualitatively similar coagulation disturbance developed in all patients, but it was more marked in patients with postoperative bleeding complications. This coagulation disturbance may be called an increased turnover of coagulation factors with reactive fibrinolysis and may be seen as the cause of the postoperative hemorrhagic diathesis. Therefore neutralization of heparin with protamine chloride at the end of ECC is contraindicated.     

Gene therapy in the central nervous system: the use of recombinant retroviruses

Only a handful of the hundreds of known vertebrate retroviruses have been deliberately subverted for use as carriers of recombinant genetic material. Retroviruses receive their name from the fact that their genome undergoes conversion from RNA to DNA following infection of a host cell. Also characteristic of retroviruses and uncommon for most other types of viruses is that the genome of the retrovirus integrates itself permanently into the DNA of the host cell. Once integrated into the host genome, the inserted provirus acts as a factory for producing more retroviral RNA genomes and expressing retroviral packaging proteins. Both components combine to form viral particles that bud from the surface of the infected cells.     

Cholinergic system during the progression of Alzheimer's disease: therapeutic implications

Alzheimer's disease (AD) is characterized by a progressive phenotypic downregulation of markers within cholinergic basal forebrain (CBF) neurons, frank CBF cell loss and reduced cortical choline acetyltransferase activity associated with cognitive decline. Delaying CBF neurodegeneration or minimizing its consequences is the mechanism of action for most currently available drug treatments for cognitive dysfunction in AD. Growing evidence suggests that imbalances in the expression of NGF, its precursor proNGF and the high (TrkA) and low (p75(NTR)) affinity NGF receptors are crucial factors underlying CBF dysfunction in AD. Drugs that maintain a homeostatic balance between TrkA and p75(NTR) may slow the onset of AD. A NGF gene therapy trial reduced cognitive decline and stimulated cholinergic fiber growth in humans with mild AD. Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.     

Transient organic mental reactions during shock therapy of the psychoses: A clinical study

Summary Recapitulating the above cases, we find that in Case 1, after two months of therapy, protracted coma followed an insulin dosage of 160 units. Previous similar dosage, with identical duration of coma, did not result in a protracted reaction following gavage. The patient had been maintained on a similar or even smaller daily insulin dosage for a considerable time prior to the protracted coma. There was consistent conformity of the electroencephalographic and psychological performances with the clinical status, all three exhibiting simultaneous improvement.In Case 2, following the fifteenth convulsive seizure, induced by 9 1/2 c.c. of metrazol, a clinically organic reaction (confusion, memory defect and disorientation) was correlated with an abnormal electroencephalogram, which became normal as the patient's clinical status returned to normal.Case 3 demonstrated the same correlation.Cases 4 and 5 revealed abnormal brain waves associated with severe memory defect.From the department of psychiatry, New York State Psychiatric Institute and Hospital. Read at the interhospital conference held at the Utica State Hospital, Utica, N. Y., April 26, 1940.     

Bromocriptine-induced behavioral hypersensitivity: implications for the therapy of parkinsonism

Bromocriptine (CB-154) is a direct-acting dopamine agonist of proven clinical efficacy in parkinsonism. The capacity of bromocriptine to induce receptor site hypersensitivity was investigated utilizing a behavioral model in guinea pigs. Following 4 weeks of bromocriptine treatment, animals demonstrated a subsequent long-lasting hypersensitivity to amphetamine and apomorphine. The data suggest that chronic use of bromocriptine can induce receptor site hypersensitivity. These results may be an indication that, because of a similar propensity to side effects during chronic therapy, direct-acting dopamine agonists will offer no long-term advantage over current antiparkinsonian drugs. The observed phenomena suggest that chronic dopaminergic agonism may not be an ideal therapy for parkinsonism.     

A case of rapid mood cycling with estrogen: implications for therapy

In a patient with a severe depressive episode that did not respond to antidepressants, rapid mood cycling abruptly developed during a clinical trial of estrogen. This association may provide a further suggestion of estrogen's antidepressant activity and its possible use in certain situations of resistant depression.     

IL-6 and CCL2 levels in CSF are associated with the clinical course of MS: implications for their possible immunopathogenic roles

Biological markers would provide valuable tools for tracking disease activity, immunopathological processes or therapeutic efficacy in MS. In this study we analysed a panel of Th(1)/Th(2) cytokines and the chemokine CCL2 in serum and CSF from MS patients and healthy controls. Increased levels of IL-6 (p<0.05) and decreased levels of CCL2 (p<0.001), with the lowest levels during acute relapses, was found in CSF from patients with relapsing-remitting MS. CSF levels of CCL2 correlated with indices for intrathecal IgG production and the CSF level of the neurofilament light protein, a marker for axonal damage, indicating a immunopathogenic role for CCL2.     

The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases

Cultured brain cells are capable of generating many molecules associated with inflammatory and immune functions. They constitute the endogenous immune response system of brain. They include complement proteins and their regulators, inflammatory cytokines, acute phase reactants and many proteases and protease inhibitors. Most of the proteins are made by microglia and astrocytes, but even neurons are producers. Many appear in association with Alzheimer disease lesions, indicating a state of chronic inflammation in Alzheimer disease brain. Such a state can apparently exist without stimulation by peripheral inflammatory mediators or the peripheral immune system. A strong inflammatory response may be autotoxic to neurons, exacerbating the fundamental pathology in Alzheimer disease and perhaps other neurological disorders. Autotoxic processes may contribute to cellular death in chronic inflammatory diseases affecting other parts of the body, suggesting the general therapeutic value of anti-inflammatory agents. With respect to Alzheimer disease, multiple epidemiological studies indicate that patients taking anti-inflammatory drugs or suffering from conditions in which such drugs are routinely used, have a decreased risk of developing Alzheimer disease. In one very preliminary clinical trial, the anti-inflammatory drug indomethacin arrested progress of the disease. New agents directed against the inflammatory processes revealed in studies of Alzheimer disease lesions may have broad therapeutic applications.     

Anti-inflammatory therapy for Alzheimer's disease: implications of the prednisone trial

The inflammatory hypothesis of Alzheimer's disease (AD), which is supported both by basic laboratory evidence and epidemiological studies, suggests that treatment with anti-inflammatory drugs may reduce the risk or slow the progression of AD. In the first large-scale test of this hypothesis, the Alzheimer's Disease Cooperative Study (ADCS) conducted a randomized placebo-controlled trial of low-dose prednisone treatment in subjects with probable AD. There was no difference in cognitive decline between the prednisone and placebo treatment groups; subjects treated with prednisone showed behavioral decline compared to those in the placebo group. While this study indicates that a low-dose regimen of prednisone is not useful in the treatment of AD, it does not refute the inflammatory hypothesis; recent evidence supports testing of a number of alternative anti-inflammatory regimens, for prevention and/or treatment of AD. The ADCS has initiated a trial to determine whether treatment with a non-selective non-steroidal anti-inflammatory drug or a selective cyclooxygenase-2 inhibitor is effective in slowing the rate of cognitive decline in AD.     

The influence of religion on sexuality: implications for sex therapy.

Religious beliefs are among the many factors that determine whether sexually dysfunctional persons will seek out a sex therapist. These beliefs may also generate resistance to therapy or influence patients to drop out of treatment before it is complete. Therapists who are sensitive to patients' religious beliefs enhance the likelihood of a successful treatment process. The authors present six case examples from their practice in which religious beliefs played an important role. They urge sex therapists to become more aware of the religious dynamic and to help address the paucity of clinical case material in the literature.     

Electroconvulsive therapy and the alpha-2 noradrenergic receptor: implications of treatment schedule effects

Six factorially designed studies evaluated the effects of different schedules of electroconvulsive shocks (ECSs) on alpha-2 adrenoceptor function in the rat brain. Attenuation of the hypomotility response to a clonidine challenge was taken to indicate alpha-2 adrenoceptor downregulation, a putative mediator of antidepressant action. Six daily and six alternate-day ECSs were shown separately to produce this receptor change. Three alternate-day ECSs produced comparable downregulation for a comparable period as six daily ECSs; this suggests that ECS produces time-dependent effects. No changes were elicited with a single ECS, which indicates that a single ECS may not influence alpha-2 receptor function. Three daily ECSs produced brief downregulation, which has implications for receptor dynamics as a function of the ECS schedule. Finally, maintenance ECSs sustained alpha-2 adrenoceptor downregulation over 6 weeks, which suggests a possible neurochemical basis for maintenance electroconvulsive therapy. The clinical relevance and scope for further research are discussed.     

Therapists' experiences of cognitive remediation therapy for anorexia nervosa: implications for working with adolescents

Cognitive Remediation Therapy (CRT) is a novel intervention developed for adults with anorexia nervosa (AN), which aims to improve "cognitive flexibility" and "holistic processing" thinking styles (Tchanturia et al., 2008; Tchanturia & Hambrook, 2009). The present study uses a qualitative approach to examine therapists' accounts of their work with inpatients suffering with AN. The objective of this study is to gain a broader understanding of how CRT has been implemented and utilized in daily life by this patient group. Therapists' letters were positive and motivational; acknowledging patients for their achievements while outlining some of the difficulties and emotions that patients experienced. Findings highlight that the majority of patients' difficulties related to their metacognitive ability and in transferring the skills to real life. Themes also concerned the processes and stages of CRT, where patients gradually drew skills from the intervention prior to making changes in their own lives. The implications of this approach for working with adolescents with eating disorders are explored. It is hoped that this study will help understanding of how CRT can be used as a treatment for AN; and how it could be developed for future work with young people.     

The effect of thymectomy and IL-1 on memory: implications for the relationship between immunity and depression

Macrophages produced proinflammatory cytokines and inflammatory responses can cause many symptoms of depression, including direct stimulation of the HPA axis and secretion of cortisol. In depressed patients, hypercortisolism has been well described as one of the major symptoms and also as the cause for hippocampal atrophy and memory impairment. In this paper, the relationships between thymectomy, increased IL-1 levels, and changes in corticosterone and neurotransmitter concentrations in rats are discussed, as well as their implications for memory impairments and depression. In thymectomized rats, deficits in both spatial and fear conditioned memory have been observed. Thymectomy decreases noradrenaline and dopamine levels, and increases serotonergic neurotransmission in limbic areas, without affecting corticosterone concentrations. In a depression model, thymopeptides or IL-2 treatment significantly attenuated changes in behavior, lymphocyte proliferation and neurotransmitters caused by bulbectomy. The reduction of thymic functions may increase IL-1 synthesis. Central IL-1beta administration impairs rat's spatial memory in the Morris water maze and 8 arms radial maze, but enhances conditioned memory in the passive avoidance. These changes can be reversed by either IL-1 receptor antagonist or a glucocorticoid receptor antagonist (RU 486). Furthermore, IL-1-induced changes in some neurotransmitter systems are similar to those observed in thymectomized rats. However, both acute and sub-chronic IL-1 administration increases plasma corticosterone concentrations. Together, these findings suggest that changes in the function of the thymus gland may play an important role in the unbalance between macrophages, cytokines, and lymphocytes, which induces neurotransmitter and neuroendocrine changes, and memory disturbances in depressive illness.