Prevalence of joint, entheseal, tendon, and bursal findings in young, healthy individuals by musculoskeletal ultrasound.

OBJECTIVE: The purpose of this study was to determine the prevalence of joint, enthesis, bursa, and tendon ultrasound findings in large and medium joints of young, healthy individuals. METHOD: Ultrasound assessment of large and medium joints, bursae, tendons, and entheses was performed in healthy individuals below the age of 30 years. Participants also underwent bioelectrical impedance analysis and conducted supervised weight training to determine maximum strength. The prevalence of ultrasound findings was calculated and a binary logistic regression model was applied to evaluate factors associated with the present findings. RESULTS: Fifty-one healthy individuals (52.9% female) with a mean age of 23.7 years were included in this study. Joint effusion in at least one joint was observed in 72.6% of the individuals (n = 37) and entheseal pathology in at least one enthesis was detected in 27.5% (n = 14). A binary logistic regression model indicated a significant association between reported hours of sports activity per week and the prevalence of effusion in the knee (p = 0.017). In addition, associations were observed between entheseal pathology in at least one entheseal site and body mass index (BMI) (p = 0.015) as well as fat mass index (p = 0.026). CONCLUSION: Joint effusion in large and medium joints, as well as entheseal hyperperfusion, bursal effusion, and tendon sheath effusion, are found in healthy individuals. Hours of sports activity per week, BMI and fat mass index showed significant associations with the findings in joints and entheses.

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep.

Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries.

BACKGROUND: Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core. METHODS: We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter. RESULTS: Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = -0.64, -0.73, 0.78, and 0.63, respectively; P<.05). CONCLUSIONS: Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque.

Cytokine secretion in squirrel monkeys.

The squirrel monkey, a non-human New World primate, has several endocrine peculiarities, including a 10-fold higher plasma cortisol concentration than Old World primates, such as man. Glucocorticoids are known to have immunomodulatory properties. We therefore measured cytokine levels in supernatants of in vitro cultures of mononuclear cells from the peripheral blood of squirrel monkeys and humans. We stimulated monocytes and lymphocytes with lipopolysaccharide (LPS) and phytohemagglutinin (PHA) in the presence or absence of hydrocortisone. Squirrel monkey monocytes secreted a more than 100-fold lower level of interleukin-1 beta (IL-1 beta) but a four-fold higher level of transforming growth factor beta (TGF-beta) than human monocytes, whereas the secretion of other cytokines, such as tumor necrosis factor alpha (TNF-alpha), TNF-beta and interleukin 2 (IL-2), did not differ between squirrel monkeys and humans. However, in squirrel monkey lymphocytes, the PHA-stimulated secretion of TNF-alpha was much greater than that of TNF-beta. Our results support the view that in squirrel monkeys there are subtle adaptations in some immune functions, particularly linked to the hypothalamic-pituitary-adrenal (HPA) system rather than a global suppression of the immune system.

High levels of circulating adrenomedullin in severe illness: correlation with C-reactive protein and evidence against the adrenal medulla as site of origin.

Adrenomedullin (AM) is a novel vasorelaxing peptide which was originally isolated from the extracts of human pheochromocytoma. It is produced by a number of organs among which the adrenal gland exhibits by far the highest concentrations. The peptide circulates in blood and its plasma levels have been reported to be increased in several diseases such as renal failure and sepsis. In the present study plasma concentrations of AM were measured in various forms of severe illness and compared to clinical and biochemical parameters in order to gain an insight into the factors controlling the plasma levels of this peptide. The highest concentrations of AM were found in patients with sepsis (344.4 +/- 60.4 pg/ml, n = 16) who exhibited up to 12-fold higher levels than a group of healthy subjects (74.1 +/- 4.1 pg/ml, n = 20). Markedly elevated levels were also measured in hemorrhagic (250.1 +/- 37.9 pg/ml, n = 9) and cardiogenic (216.2 +/- 29.4 pg/ml, n = 7) shock as well as in patients with cancer of the gastrointestinal tract (155.6 +/- 32.5 pg/ml, n = 11) or the lungs (146.5 +/- 19.1 pg/ml, n = 22). Plasma AM levels were positively correlated with serum creatinine concentrations in shock (r = 0.06, p < 0.001) and with C-reactive protein levels in patients with cancer (r = 0.64, p < 0.001) or sepsis (r = 0.63, p < 0.01). In order to examine the potential role of the adrenal gland as a site of AM release, hypoglycemia was induced in a group of healthy volunteers by graded infusion of insulin. Despite a more than 20-fold increase in plasma adrenalin indicating maximal stimulation of the adrenal medulla, no significant alterations of the plasma AM levels were observed. The study demonstrates that not only sepsis but also various forms of cancer and shock are associated with high levels of circulating AM. The correlation with C-reactive protein levels suggests a role of cytokines in mediating the elevations in plasma AM observed in sepsis and cancer. Reduced clearance of the peptide by the kidneys may be one of the mechanisms involved in the accumulation of AM in shock. The adrenal gland appears not to be a major source for circulating AM.

Auditory responsive cortex in the squirrel monkey: neural responses to amplitude-modulated sounds.

The neural response to amplitude-modulated sinus sounds (AM sound) was investigated in the auditory cortex and insula of the awake squirrel monkey. It was found that 78.1% of all acoustically driven neurons encoded the envelope of the AM sound; the remaining 21.9% displayed simple On, On/Off or Off responses at the beginning or the end of the stimulus sound. Those neurons with AM coding were able to encode the AM sound frequency in two different ways: (1) the spikes followed the amplitude modulation envelopes in a phase locked manner; (2) the spike rate changed significantly with changing modulation frequencies. As reported in other species, the modulation transfer functions for rate showed higher modulation frequencies than the phase-locked response. Both AM codings exhibited a filter characteristic for AM sound. Whereas 46.6% of all neurons had the same filter characteristic for both the spike discharge and the phase-locked response, the remaining neurons displayed combinations of different filter types. The discharge pattern of a neuron to simple tone or noise bursts suggests the behaviour of this neuron when AM sound is used as the stimulus. Neurons with strong onset responses to tone/noise bursts tended to have higher phase-locked AM responses than neurons with weak onset responses. The spike rate maxima for AM sound showed no relation to the tone/noise burst discharge patterns. Varying modulation depth was encoded by the neuron's ability to follow the envelope cycles and not by the non-phase-locked spike rate frequency. The organization of the squirrel monkey's auditory cortex has previously been established by an anatomical study. We have added two new fields using physiological parameters. All fields investigated showed a clear functional separation for time-critical information processing. The best temporal resolution was shown by the primary auditory field (AI), the first-temporal field (T1) and the parainsular auditory field (Pi). The neural data in these fields and the amplitude modulation frequency range of squirrel monkey calls suggest a similar correlation between vocalization and perception as in human psychophysical data for speech and hearing sensation. The anterior fields in particular failed to follow the AM envelopes. For the first time in a primate, the insula was tested with different sound parameters ranging from simple tone bursts to AM sound. It is suggested that this cortical region plays a role in time-critical aspects of acoustic information processing. The observed best frequencies covered the same spectrum as AI. As in the auditory fields, most neurons in the insula encoded AM sound with different filter types. The high proportion of neurons unable to encode AM sound (40.6%) and the low mean best modulation frequency (9.9 Hz) do not support a prominent role of the insula in temporal information processing.

Lipopolysaccharide increases EEG delta activity within non-REM sleep and disrupts sleep continuity in rats.

Activation of the immune system by microorganisms or specific microbial constituents promotes non-rapid-eye-movement (REM) sleep (non-REMS). In this study, we assessed the effects of lipopolysaccharide (LPS) on sleep duration, electroencephalogram (EEG) power spectra, and brain temperature (Tbr) in rats. Twenty-four hour recordings were made before and after intraperitoneal injection of vehicle or 30 or 100 micrograms/kg LPS at lights on. During the first 12 h after administration of both doses of LPS, Tbr was elevated, REMS duration was reduced, and non-REMS duration was unchanged, whereas the non-REMS episodes were shortened. EEG activity within non-REMS from 0.5 to 7 Hz was enhanced during hours 3-12. During the second 12-h period, the number of non-REMS and REMS episodes and the total time in both states were increased. EEG activity within non-REMS was mainly reduced in the entire frequency range (0.5-25.5 Hz). The effects of LPS did not differ between the doses. The effects of LPS on EEG power spectra are similar to those observed after sleep deprivation, i.e., a physiological intensification of non-REMS, indicating that both manipulations may activate common sleep EEG regulatory mechanisms. However, the disruption of non-REMS continuity following LPS administration at light onset contrasts the changes induced by sleep deprivation and may reflect an effect of a systemic inflammatory response on sleep maintenance.

Effect of bacterial endotoxin and interleukin-1 beta on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study.

In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS-treated animals. The effects of i.p. LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c.v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural encoding of amplitude modulation within the auditory midbrain of squirrel monkeys.

The neuronal responses to amplitude modulated (AM) sounds were investigated in the auditory midbrain of the squirrel monkey. Sinusoidally modulated tones and noise served as acoustic stimuli. In order to describe the response properties of collicular neurons, Fast-Fourier-Transformation (FFT), a cross-correlation algorithm and spike-rate counts were applied to translate the neuronal reactions into modulation transfer functions. FFT and cross-correlation defined a measure for synchronicity of the neuronal discharges with the modulation cycles. All neurons (542) responded selectively to AM-sounds insofar as all displayed a best modulation frequency (BMF). Most of them furthermore had a band-pass-like modulation transfer function, whose center frequencies were mainly between 8 and 128 Hz. Transfer functions obtained by spike-rate showed less selectivity: a relatively great number of neurons did not change their spike rate as a function of modulation frequency. The results show that encoding of amplitude-modulated sounds occurs to a greater extent via phase locking of discharges than via changes in spike number. In the same way, changing modulation depth is processed: whereas spike rate on average remains constant between 100% and 0% modulation, there is a drastic reduction in synchronicity. No clear relationship was found between a unit's characteristic frequency and BMF; the same applied to BMF and recording place. The results furthermore show that amplitude modulations are encoded selectively in a band pass function in a non-human primate. The midbrain thereby occupies an intermediate position within the pathway from the periphery to the cortex. This form of temporal resolution probably underlies mechanisms caused by the increasing synaptic activity in the course of the pathway. This may indicate adaptation since those modulation frequencies embedded in this species' vocal repertoire fit quite well with the system's tuning properties for amplitude modulation.

Pregnenolone enhances EEG delta activity during non-rapid eye movement sleep in the rat, in contrast to midazolam.

Several endogenous steroids exert their neuroactivity through non-genomic effects and act as potent GABAA receptor-agonists or-antagonists. To examine the influence of the main precursor of these steroids on sleep-wake behaviour, pregnenolone (400 micrograms) was dissolved in oil and administrated s.c. to 8 rats at the beginning of the light period. For comparison, the benzodiazepine midazolam was also injected (3 mg/kg). The effects on the amounts of the vigilance states and on the EEG signals within each state were investigated during 24 hours. Compared to control vehicle, pregnenolone did not significantly affect the duration of the vigilance states. However, delta activity (0.5-4 Hz) within non-rapid eye movement sleep (nonREMS) was enhanced throughout the recording period. Midazolam increased nonREMS, decreased wakefulness and, transiently, also suppressed rapid eye movement sleep (REMS). Spectral analysis of the EEG within nonREMS showed a long lasting reduction in delta and theta activity (4-9 Hz) and a shorter lasting enhancement in the higher frequencies (10-25 Hz). EEG activity within REMS and wakefulness was elevated in the higher frequencies (> or = 10 Hz) during the the first half of the recording period. We conclude that in the rat, the effects of midazolam on EEG activity closely resemble those of benzodiazepines in other mammalian species. The influence of pregnenolone on EEG delta activity within nonREMS indicates that pregnenolone acts as an inverse GABAA-benzodiazepine agonist.

[Head lice infestation in the Cottbus district]. / Untersuchungen zum Kopflausbefall im Bezirk Cottbus.

670 children of infant-schools and 109 children of schools were examined for head-lice. Also the existence of nits was valued. The identified infestation of 9.9% is to stimulate examinations in other districts of GDR and measures to form the search and the control of these ectoparasites with more effects.

Processing of amplitude modulated sounds in the medial geniculate body of squirrel monkeys.

The responses of single and multi units in the medial geniculate body of the squirrel monkey (Saimiri sciureus) to modulation frequency, modulation depth and changes in absolute intensity of sinusoidally amplitude modulated (AM) sounds were studied. Both spike-frequency and spike rate modulation were used as a measure for neuronal response. Spike rate modulation was derived from FFT (Fast-Fourier-Transformation) analysis of the PSTHs. In all cases (N = 133) spike rate modulation was shown to be dependent on the stimulus modulation frequency: Most neurons responded best to one modulation frequency, i.e., they showed a modulation transfer function with bandpass characteristic; only a few displayed a low pass or multiple peaked transfer characteristic. The majority of the neurons responded best in a range from 4 to 64 Hz, with a peak at 32 Hz and a median at 16 Hz. Such modulation frequencies are common in parts of the species vocal repertoire.

Cytostatic extravasations.

Sixty-six cases of cytostatic extravasation referred to a plastic surgery department between 1977 and mid-1985 are discussed. Doxorubicin was the most common drug involved, but a number of other drugs also caused lesions requiring surgical intervention. Operative treatment, consisting of excision of drug-infiltrated tissue followed by skin transplantation, was performed in half the patients. Significant residual damage was seen in 12 patients who had all received the drug at the elbow joint, wrist, or back of the hand. Fourteen patients were operated on late in the course of the disease, on average 10 weeks after the accident because of delayed referral. In 1983 prophylaxis was undertaken and first-aid treatment was administered, consisting of aspiration via the administration catheter. The nature of patient referrals then improved considerably. It is recommended that cytostatic treatment be given at the antebrachium, if possible, and that aspiration be attempted promptly after an accident. Manifest lesions should be operated on early, i.e., within the first week. The indication for early operation is particularly strong if a highly irritative drug has been deposited in a critical region and has caused a severe local reaction.

Searching for neural correlates of the hearing sensation fluctuation strength in the auditory cortex of squirrel monkeys.

Sounds with slow (less than 20 Hz) fluctuations may elicit the hearing sensation fluctuation strength. For AM tones, neural correlates of fluctuation strength were searched in the auditory cortex of unanesthetized squirrel monkeys. To enable a comparison of psychophysical and physiological data, the 'modulation' of the peristimulus time histogram was fitted by a sinusoidal function. The dependence of the amplitude of this function on modulation frequency, modulation depth and sound pressure level was often comparable to the dependence of fluctuation strength on the same stimulus parameters. In particular, as a function of modulation frequency, the neural data also show a bandpass characteristic at low modulation frequencies as was found for the hearing sensation fluctuation strength.

On the mechanisms of call coding through auditory neurons in the squirrel monkey.

The main goal of the study was to investigate the neural processing of those acoustic signals through auditory neurons whose relevance for communication is either obvious or has been tested by psychoacoustic or behavioral experiments. Thus the activity of cortical, thalamic (MGB) and midbrain (IC) neurons of the auditory pathway were studied with periodically amplitude-modulated (AM) sounds, species-specific AM vocalizations and self-produced vocalizations. With regard to the processing of AM stimuli, there is evidence of a neural correlate to the psychoacoustic phenomenon "fluctuation strength": maximum of the Best Modulation Frequency (BMF) for the cortex was registered at 4 Hz. Furthermore, a relatively large number of units within the IC and the MGB can encode such amplitude changes which have been shown to be of communicative function; here too a neural correlate to the encoding processes of species-specific calls was indicated. Self-produced vocalizations do not seem to underlie a specific processing except that in higher auditory structures, they evoke quantitatively lower responses. In the midbrain, such less active areas are rare and were localized in regions belonging more to secondary auditory structures than primary ones.