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Biomedical subjects

J C Krieg

Publications and source records attributed to J C Krieg.

116 records · Page 7Linked to original sources

The Munich vulnerability study on affective disorders: overview of the cross-sectional observations at index investigation.

BACKGROUND: An altered nocturnal sleep pattern and a dysfunction of the hypothalamic-pituitary-adrenocortical system are neurobiological abnormalities typical for depression. A persistence of these neurobiological alterations during remission has been shown to be associated with an increased risk for a relapse. However, it remains unclear whether these persisting abnormalities are trait markers indicative of an increased vulnerability for affective disorders or only represent 'biological scars' acquired during past episodes. Thus, respective examinations need to be performed in the premorbid state in order to answer this open question. METHODS: In the present article we have summarized the various results of the index investigation of a prospectively designed study in which we investigated 54 healthy first-degree relatives (high-risk probands; HRPs) of patients with an affective disorder using polysomnography, the combined dexamethasone corticotropine-releasing hormone (DEX-CRH) test and psychometric measurements. RESULTS: In the cross-sectional part of this study the HRPs, as a group, exhibited a 'depression-like' sleep EEG profile and DEX-CRH test result, while their psychometric profile was characterized by elevated scores on the measures 'Rigidity' and 'Autonomic lability'. On an individual level, 35% of the HRPs were identified as conspicuous in at least two of the three areas under investigation. CONCLUSIONS: The question of whether these abnormalities do indeed reflect trait markers indicative of an increased vulnerability for depression will be answered by the longitudinal part of the study that allows for the retrospective identification of the premorbid status of those HRPs who develop an affective disorder during the follow-up period.

Adolescent↗

Regulation of glucocorticoid receptor-mRNA in human blood cells by amitriptyline and dexamethasone.

Recent research suggests that antidepressants exert their clinical action in depression via the restoration of glucocorticoid receptor (GR) function with a subsequent normalization of the altered feed-back regulation of the hypothalamic-pituitary adrenocortical (HPA) system. We, therefore, studied the effects of amitriptyline, a standard antidepressant, and of the glucocorticoid dexamethasone, which has recently been reported to possess antidepressive properties, on glucocorticoid receptor mRNA (GR-mRNA) derived from blood cells of healthy male volunteers. Whole blood samples were exposed in vitro for 24 h to amitriptyline and dexamethasone, the mRNA was extracted, transcripts of the 'house-keeping gene' glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the GR-gene were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) and semiquantitatively determined by subsequent densitometry. In a concentration of 10 nM, amitriptyline induced a significant increase in GR-mRNA (GR/GAPDH ratio) to 186 +/- 31% of the control condition, while a concentration of 10 microM of amitriptyline resulted in an increase of GR-mRNA (GR/GAPDH ratio) to 165 +/- 36%. Dexamethasone also up-regulated blood cell GR-mRNA (GR/GAPDH ratio) levels at a concentration of 10 nM to 184 +/- 29%, whereas an incubation with 10 microM apparently resulted in toxic effects on blood cells with a decreased amount of total mRNA samples recovered. In conclusion, we here show an increase of GR-mRNA in human blood cells after treatment with amitriptyline and dexamethasone, pointing to a direct action of these substances on GR-gene expression in a human system.

Adult↗

Stimulus sensitivity and neuromodulatory properties of noisy intrinsic neuronal oscillators.

Intrinsic subthreshold oscillations in the membrane potential are a common property of many neurons in the peripheral and central nervous system. When such oscillations are combined with noise, interesting signal encoding and neuromodulatory properties are obtained which allow, for example, sensitivity adjustment or differential encoding of stimuli. Here we demonstrate that a noisy Hodgkin/Huxley-model for subthreshold oscillations, when tuned to maximum sensitivity, can be significantly modulated by even minor physiological changes in the oscillation parameters amplitude or frequency. Given the ubiquity of subthreshold oscillating neurons, it can be assumed that these findings reflect principle encoding properties which are relevant for an understanding of sensitivity and neuromodulation in peripheral and central neurons.

Action Potentials↗

Pain perception in patients with eating disorders.

The heat pain threshold was measured with phasic and tonic stimuli under basal conditions and after naloxone administration in 10 anorectic and 10 bulimic patients as well as in 11 healthy control subjects. Under both kinds of stimulation, the basal threshold values were elevated in the bulimic patients and in some of the anorectic patients. Naloxone did not differ from placebo in its effect on the pain thresholds (phasic and tonic), suggesting that a nonopioid mechanism was responsible for the threshold elevation found in the eating disorder patients. The plasma cortisol concentration was similar in the three groups and not correlated with the basal pain thresholds in the patients. Other indicators of dieting such as beta-hydroxybutric acid and triiodothyronine also showed no correlation with the basal pain thresholds. Significant height correlations can be interpreted as weak evidence that neuropathy is the cause of the increase in the pain threshold.

Adult↗

Pain perception in depression: relationships to symptomatology and naloxone-sensitive mechanisms.

A decrease in pain sensitivity during acute depression has been observed in several studies, apparently related to the severity of symptomatology. However, the question remains whether this relationship can be found only in heterogeneous groups of depressive patients or also in a single diagnostic group, such as major depression. In the present study, pain thresholds were assessed in 20 patients with major depression (DSM-III-R) and in 20 healthy controls. Two threshold methods with a differing impact of reaction time on the results were used. Contact heat was applied as a natural source of pain. With both methods the pain thresholds were significantly increased in the depressive patients. No relationship was found to the various symptoms of depression assessed by psychopathometric scales. In contrast to the pain thresholds, the thresholds of skin sensitivity for nonnoxious stimuli (warmth, cold, vibration) were only slightly increased. In subsamples (N = 10 in each group), naloxone (5 mg i.v.) and placebo were administered in a double-blind design. No systematic changes in pain thresholds occurred under either treatment. Our findings suggest that the decrease in skin sensitivity in major depression is specific to pain and not due to an increased reaction time. Moreover, the decrease appears to be related neither to a naloxone-sensitive mechanism nor to symptomatology.

Adult↗

Relationship between clinical pain complaints and pain sensitivity in patients with depression and panic disorder.

OBJECTIVE: There is evidence that depression and panic disorder are both associated with an increased frequency of clinical pain complaints. A change in pain sensitivity is alleged to be involved in this phenomenon. However, few studies have assessed clinical pain complaints and pain sensitivity in the same group of patients. METHODS: Thirteen patients with a major depressive disorder, 13 patients with a panic disorder (diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition), and 13 healthy control subjects were investigated. None of the subjects were taking medications. Body maps were used to measure the number of painful sites as well as the intensity and unpleasantness of pain complaints in the previous 6 months. Furthermore, pain thresholds for pressure, cold, and heat were assessed at the forearm or hand. RESULTS: Patients with depression and panic disorder had significantly more frequent, more intense, and more unpleasant pain complaints than healthy control subjects. Despite this similarity, patients with depression had significantly higher pain thresholds than patients with panic disorder in two (pressure and cold) of three stimulus modalities and significantly higher pressure pain thresholds than the healthy control subjects. There were no differences between the pain thresholds of patients with panic disorder and healthy control subjects. The correlations between clinical pain measures and pain thresholds were generally weak. CONCLUSIONS: These findings suggest that the clinical pain complaints of patients with depression and panic disorder cannot simply be explained by changes in pain sensitivity.

Adult↗

Cervical spine arthrodesis in rheumatoid arthritis: a long-term follow-up.

Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient's medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time.

Arthritis, Rheumatoid↗