Expression of CD11b/CD18 adhesion molecules on circulating phagocytes-a novel aid to diagnose infection in patients with cancer.

GOALS OF WORK: No blood marker available to date is useful for distinguishing infection-related from neoplasm-related fever. We evaluated the expression of the peripheral blood phagocyte CD11b/CD18 adhesion molecule complex for this purpose. MATERIALS AND METHODS: Neutrophil and monocyte CD11b/CD18 expression was assessed in two cohorts of patients with advanced solid cancer (n = 120) and in healthy controls (n = 63). The cancer series included 89 patients with verified infection, 23 without infection, and eight with neoplastic fever. CD11b/CD18 expression was measured using flow cytometry, and serum C-reactive protein (CRP) concentration was determined with immunoturbidimetric assay. RESULTS: Cancer patients with infection had higher blood neutrophil and monocyte CD11b/CD18 expression levels than patients with neoplastic fever, those with advanced cancer without infection, or healthy controls (p < 0.01 for all analyses). High CD11b/CD18 values were measured exclusively in individuals diagnosed with infection. Receiver-operating characteristic area under the curve (AUC) for neutrophil and monocyte CD11b/CD18 expression for the discrimination of infection from neoplastic fever was 0.80 (95% CI, 0.70 to 0.88), which was superior (p = 0.039 and p = 0.049, respectively) to serum CRP on admission (AUC 0.51, 0.40 to 0.62). CONCLUSIONS: Peripheral blood phagocytic cell CD11b/CD18 expression is useful for making a differential diagnosis between infection and neoplasm-related fever in cancer patients.

Preoperative postural control of patients with vestibular schwannoma assessed by visual feedback posturography.

BACKGROUND: The need for an objective method to describe the functional postural control of patients with vestibular schwannoma in agreement with their subjective sensation of balance. OBJECTIVES: The objective was to compare the postural control of 49 patients with unilateral vestibular schwannoma (VS) with that of healthy subjects by using visual feedback posturography (VFP). We aimed to find out if preoperative postural control of the patients correlates with their subjective sensation of balance. METHODS: In the VFP, while standing on the platform, patients were instructed to move their center of gravity (COG) marker to the targets as fast and accurately as possible. Hit delay (HD) to the targets, hold percentage (HP) within the targets, COG marker velocity (CMV) to the targets, and balance index (BI) were calculated. We rated intensity of balance disturbance using a 5-point qualitative scale. RESULTS: Twenty-two (45%) patients had at least one abnormal VFP parameter, and 49% of patients were simultaneously symptomatic. Mean hit delay (HD), hold percentage (HP), and balance index (BI) were significantly worsened in patients with VS (p < 0.05). Increased HD and BI correlated significantly with subjective sensation of imbalance (p = 0.02). CONCLUSIONS: The overall deficit in preoperative postural control of the VS patients was not severe, and this finding agreed well with their subjective sensations.

Peripheral blood phagocyte CD14 and CD11b expression on admission to hospital in relation to mortality among patients with community-acquired infection.

OBJECTIVE AND DESIGN: Prognostic value of markers of systemic inflammation were evaluated in patients admitted to hospital. MATERIAL: The study comprises 327 patients with community- acquired infection verified on admission (n=290) or within 3-day follow-up (n=37). METHODS: On-admission levels of phagocyte CD11b/CD18 and CD14 expression were measured using whole blood flow cytometry. Clinical data were collected retrospectively from medical records. RESULTS: In univariate analysis, non-survivors as compared to survivors had higher age, lower arterial pressure, higher heart rate, and lower monocyte CD14 density. In multivariate analysis high age [relative mortality RR 1.05 (95% CI 1.01 to 1.08), p=0.016] and low CD 14 expression on monocytes [RR 7.49 (CI 1.63 to 34.33), p=0.01] remained predictive for the 28-day mortality. CONCLUSION: In patients with community-acquired infection, low on-admission level of monocyte CD14 is related to fatal outcome.

Laboratory markers of systemic inflammation as predictors of bloodstream infection in acutely ill patients admitted to hospital in medical emergency.

The aim of the present study was to determine whether the presence of an infectious focus or of fever alone can predict bloodstream infection and whether levels of C-reactive protein, procalcitonin, interleukin (IL)-6, IL-8, and soluble IL-2 receptor (sIL-2R) improve the diagnosis of community-acquired bloodstream infection. Markers of systemic inflammation were studied in 92 patients with community-acquired infection. On admission to hospital, 54 patients had an infectious focus, 25 had fever without an infectious focus, and 13 had neither. The presence of focus or fever predicted bloodstream infection (n=13 patients) with a sensitivity of 100% (95% confidence interval, 75-100), a specificity of 16% (95%CI, 9-26), a negative predictive value of 100% (95%CI, 75-100), and a positive predictive value of 16% (95%CI, 9-26). Positive predictive values of C-reactive protein, procalcitonin, IL-6, IL-8, and sIL-2R, all measured on admission, were also low (33-44%). Eight febrile patients in whom an infectious focus was found during a 3-day follow-up period had higher on-admission IL-6 (P=0.005) and sIL-2R (P=0.046) levels than did 17 febrile patients without an infectious focus. In conclusion, markers of systemic inflammation do not improve the diagnosis of community-acquired bloodstream infection; however, they may aid in identifying patients with fever due to occult infection.

Subclinical vestibulocerebellar dysfunction in migraine with and without aura.

OBJECTIVE: In patients with migraine, neurotologic symptoms and signs occur commonly. The authors' aim was to determine whether neurotologic findings are in accordance with the type of migraine and whether test findings differ from those of healthy controls. METHODS: The authors examined 36 patients with various types of migraine classified by International Headache Society criteria. Comprehensive neurotologic tests were performed between attacks: video-oculography (VOG), electronystagmography, static posturography, and audiometry on 12 patients with migraine with aura (MA) and 24 patients with migraine without aura (MO). Results were compared to those of test-specific nonmigrainous control groups. Only eight migraineurs (six with MA and two with MO) had vertigo or dizziness. RESULTS: Despite the absence of clinical neurotologic symptoms, most of the patients with migraine (83%) showed abnormalities in at least one of these tests. Both migraine types differed significantly from the control group (in VOG, in saccadic accuracy, and in static posturography). Vestibular findings tended to be more severe in MA than in MO. CONCLUSIONS: These data suggest that interictal neurotologic dysfunction in MA and MO share similar features and that the defective oculomotor function is mostly of vestibulocerebellar origin.

Motorized head impulse stimulator to determine angular horizontal vestibulo-ocular reflex.

The objective of the current study was to develop a computer-controlled mechanical system for the generation of impulsive head rotations to measure eye movements induced by angular horizontal vestibulo-ocular reflex. This is a clinical eye movement test recently introduced for the usage of otoneurological balance laboratories. We built the system and modified our prior computer software developed for other types of eye movement tests. Motor controlled stimulation has fulfilled the requirement of more uniform and constant acceleration stimulation than obtained with manually administrated impulses. After having executed preliminary experiments at our balance laboratory we found the system to be efficient, reliable and secure.

Postural control as assessed with virtual reality.

We studied the use of virtual reality technology as a stimulus in balance examinations. A pilot study was made using a small group of healthy subjects to investigate the effect of alcohol and virtual reality stimulus on the subjects' balance. The tests showed that blood alcohol concentration accounted for almost 50% of the increased lateral body sway velocity. The new stimulus technique based on virtual reality technology seems to be effective and flexible for postural investigations.

Towards virtual reality stimulation in force platform posturography.

We developed a stimulation technique on the basis of virtual reality methods for balance investigation performed in balance laboratories of otorhinolaryngological clinics and institutes of occupational health. Such a stimulation technique is greatly progressive in the sense that by creating virtual moving views and "virtual worlds" inside which the subject is located it is possible to make effective stimuli that would be very difficult or even impossible to set in any real environment. We tested our system on healthy subjects and found out that this kind of virtual reality stimulation system is very useful for balance analysis.

Increased retinal image velocity after vestibular lesion.

The vestibulo-ocular reflex stabilizes gaze during head movements by producing compensatory eye movements. Retinal image velocity (RIV) is defined as the difference between the eye and head velocities. The RIV of 20 vestibular schwannoma (VS) patients and 17 healthy controls was measured with a head autorotation test. The head autorotation test had a sensitivity of 80% and a specificity of 88%. The mean RIV (degree/second) +/- 95% confidence intervals of the VS patients in the 5 frequency bands of 1 to 5 Hz was respectively 4.8 (4.2 to 5.5), 11.5 (8.6 to 14.4), 21.7 (15.5 to 27.9), 25.2 (17.1 to 33.4), and 26.1 (13.1 to 39.1). The RIV of the VS patients was asymmetrically larger on the operated side (P<0.05) in the frequency band of 1 Hz. The mean RIV was significantly (P<0.05) larger in the VS patients than in the controls in the frequency bands of 1 to 4 Hz. The vestibulo-ocular reflex is inaccurate after VS surgery; but the inaccuracy may not lead to the occurrence of any symptoms.

Decreased vestibulo-ocular reflex gain of vestibular schwannoma patients.

OBJECTIVE: The vestibulo-ocular reflex (VOR) stabilizes gaze during head movements by producing compensatory eye movements. Gain of the VOR can be defined as the difference between the eye and corresponding head movement amplitudes. The objective of the study was to compare the gain of postoperative vestibular schwannoma (VS) patients with that of healthy controls. METHODS: The gain of 19 vestibular schwannoma (VS) patients and 100 healthy controls was measured with a head autorotation test (HART) in the five frequency bands of 1-5 Hz. It was computed as the ratio of the amplitude of the eye position signal to the amplitude of the head position signal. The mean gain was compared between the VS patients and healthy subjects in each frequency band by using an analysis of variance with statistical significance pre-defined as P < 0.05. RESULTS: The HART was abnormal in 58% of the VS patients, whose mean gains in the five frequency bands of 1-5 Hz were 0.85, 0.79, 0.72, 0.64 and 0.60, respectively. The mean gains of the VS patients were significantly (P < 0.05) smaller than those of the controls in all the frequency bands. CONCLUSIONS: The deficit of the VOR gain seems to prevail in more than a half of postoperative VS patients, although this inaccuracy of compensatory eye movements may not lead to the occurrence of any symptoms. However, in these patients a potential threat to gaze stability exists.

Effects of digital filtering on the parameters of impulse-like eye movements.

Influence of two filtering modes were researched with electro-oculographically recorded impulse-like eye movements. Linear finite impulse response (FIR) and non-linear hybrid median filters were explored by considering gain and latency parameters that yield the most important information in the case of these eye movements. It is stated that carefully selected lowpass filtering can securely be run without considerable changes in parameter values in order to discard noise stemming from physiological or other reasons.

Comparison of two head autorotation tests.

The head autorotation test is a novel method for studying the high-frequency vestibuloocular reflex without heavy machinery to generate whole-body rotation. Despite many studies with the test, the method is far from standardized, and no comparison has been made of different versions of the test. The objective of this study was to compare the vestibuloocular reflex of 100 healthy subjects measured simultaneously with two versions of the head autorotation test. Gain, phase, asymmetry, and the frequency bands reached were determined in the frequency bands of 1, 2, 3, 4, and 5 Hz. The gain measured with both tests was close to unity (range 0.95-1.04) from 1 to 4 Hz and about 0.9 at 5 Hz. In the test developed by Vorteq the phase lagged (-7 to -21 degrees) in all the frequency bands, and it differed significantly from the phase lead of 2 to 5 degrees that was measured by the other test. The asymmetry measured with the Vorteq test increased continuously from 1.5% (1 Hz) to 5.7% (5 Hz). The results of the tests showed intersubject variation, which was larger in the higher frequency bands. In conclusion, the high-frequency vestibuloocular reflex of healthy subjects can be quantified with active head oscillation. Both tests produced similar gain results, but the phase results differed systematically. Thus, the results of different head autorotation tests may not be directly comparable.

Postural compensation after intratympanic gentamicin treatment of Menière's disease.

We have treated 93 patients with severe Menière's disease with gentamicin (GM) applied with 1 to 4 or intratympanic injections in a prospective study. The patients were tested at frequent intervals and followed up for two years. Postural stability was evaluated on posturography. Unsteadiness and gait between attacks, working capacity and vertigo were scored. Before commencing the treatment 47 of the patients complained from moderate to severe postural instability. After treatment moderate to severe postural instability was met in 19 patients. Initially the sway velocity was 27 mm/s on average being significantly worse than in referents. Two weeks after treatment the sway velocity increased to 33 mm/s. Thereafter the sway velocity slowly started to decline to 31 mm/s after two years. Patients with severe attacks of rotatory vertigo had a good postural outcome with GM treatment. In logistic regression analysis the most significant risk factor for poor recovery after GM treatment was severely reduced gait before commencing the treatment with odds ratio of 2.0. Subjectively, after two years, the patients rated their postural stability significantly improved when compared to pretreatment values. The good subjective rating of postural stability is related to postural training program where in the absence of attacks, the patients have learned to cope with daily tasks.

Effect of intratympanic gentamicin on hearing and tinnitus in Meniere's disease.

OBJECTIVE: The objective of this study was to examine the effect of intratympanically applied gentamicin (GM) (30 mg/mL) on hearing and tinnitus in patients with intractable Meniere's disease. STUDY DESIGN: A prospective study was conducted on 93 subjects treated with intratympanically applied GM. The mean pure-tone average (PTA) at speech frequencies was measured before the treatment and after 2 weeks, 1 month, 3 months, 6 months, 1 year, and 2 years after injections. Tinnitus was surveyed with a questionnaire. The mean duration of Meniere's disease was 9.8 years (range, 1-33 years). PATIENTS: The study group consisted of 28 men and 65 women. The mean age was 50.9 years (range, 19-74 years). RESULTS: The mean PTA at speech frequencies for the group worsened from 60 dB to 68 dB, which was statistically significant. Ten ears were deafened. The mean tinnitus handicap score before treatment was 2.92; 2 years after treatment, it was 2.26, indicating significant abatement of tinnitus during the course of the treatment. CONCLUSIONS: The authors found that the average frequency of deafening was 10% and it was dose dependent. GM caused alleviation of tinnitus in the majority of the patients.

A signal analysis method for impulse-like eye movements.

Eye movement investigations are performed in several fields of medicine. We have developed signal analysis methods of eye movements studied in otoneurology for several years. Previously, we have designed methods for eye movement types of saccades, nystagmus, smooth pursuit, and vestibulo-ocular reflex. In this paper we extend and develop further our method to concern also impulse-like eye movements, i.e. a new type of eye movement tests for investigations of vertiginous patients. According to our preliminary results the use of our method is efficient to differentiate patients with inner ear diseases from normals.

One-footed and externally disturbed two-footed postural control in patients with chronic low back pain and healthy control subjects. A controlled study with follow-up.

STUDY DESIGN: A study of postural control during one-footed and externally disturbed two-footed stance among healthy control subjects and patients with chronic low back pain at the beginning of a functional back restoration program and 6 months later at follow-up examination. OBJECTIVES: To study postural control cross-sectionally among control subjects and patients with low back pain, and to evaluate the effects of functional restoration on the postural control parameters in a follow-up examination. SUMMARY OF BACKGROUND DATA: Deficits of motor skills and coordination have been reported in association with musculoskeletal disorders. It has been found that patients with chronic low back pain have impaired psychomotor control, but the impairment is reversible with successful low back rehabilitation. It is insufficiently known how functional activation and intensive physical training affect postural control. METHODS: Sixty-one healthy volunteers (32 men, 29 women) and altogether 99 patients with low back pain participated in the study. Sixty-eight patients (33 men, 35 women) had moderate and 31 (18 men, 13 women) had severe low back pain. Postural stability was measured with a force platform. In two-footed stance, vibration stimulation on calf and back muscles was used to disturb the balance. Center point of force-velocity (cm/sec), average position shift in anteroposterior direction (cm), and maximal position shift in lateral direction (cm) were used as the parameters. RESULTS: Reliability of all tests was acceptable. Center point of force-velocity was the most sensitive parameter and the one-footed measurement the most sensitivetest for evaluating postural stability. At the beginning, the patients with severe low back pain had poorer one-footed postural control compared with the control subjects (P = 0.0003). The subgroup of patients with moderate low back pain participated in the restoration program. The outcome of the restoration program was considered good if the disability because of low back pain (Oswestry index) decreased during the restoration program and poor if the disability increased or did not change. The one-footed postural stability remained primarily at the same level as the initial results in the control and good outcome groups, but became significantly poorer in the poor outcome group. The difference between poor outcome and control groups was statistically significant (P = 0.04). CONCLUSIONS: Impaired postural stability seems to be one factor in multidimensional symptomatology of patients with chronic low back trouble. Postural stability is easily disturbed in case of impairment in strength, coordination, or effective coupling of muscles in the lumbar and pelvic area. Patients with chronic low back pain seem to experience impairment in these functions, which should be taken into consideration when back rehabilitation programs are planned.

Intratympanic gentamicin in Meniere's disease.

Ninety-three patients with intractable Meniere's disease were treated with gentamicin (Garamycin 40 mg/ml) administered in 1 to 4 transtympanic injections. The patients were tested at frequent intervals and followed up for 2 years. Before treatment all subjects experienced moderate or severe handicap caused by Meniere's disease. Two years after the treatment, rotatory vertigo was abolished in 81% of subjects, Tumarkin attacks were cured in 60%, and work capacity was severely reduced in 10% and moderately reduced in 17% of subjects. The outcome of the caloric responses did not correlate with the outcome of the treatment. In logistic regression analysis poor outcome of treatment correlated with Tumarkin attacks (odds ratio 5.5), severity of vertigo (odds ratio 3.8) and gait disorders (odds ratio 2.9). The mean hearing level was significantly affected by the treatment (before, 59.1 dB HL; after, 67.9 dB HL). Ten treated ears became deafened. During follow-up 44 subjects were subjected to retreatment, usually after 6 months. Intratympanic gentamicin treatment is a relatively safe and effective way to treat Meniere's disease. The authors recommended starting with 2 injections and renewing the injections if relapse occurs.

A head autorotation test for patients with Menière's disease.

OBJECTIVE: We compared the vestibulo-ocular reflex (VOR) of healthy volunteers and of two groups (group A, conservatively treated; and group B, with gentamicin or surgically treated) of Menière's disease (MD) patients to determine whether the head autorotation test (HART) can reveal abnormality of the VOR and whether the HART can be applied in evaluation of MD. METHODS: The gain, phase, asymmetry, and the highest frequency band reached was evaluated with the HART in the frequency range of 1-5 Hz. The caloric responses and posturography results were also determined. RESULTS: The mean gain was lower for the both groups of MD patients than for the controls. In the MD patients the phase difference was shorter and the asymmetry was greater than in the controls. Only 58% (group A) and 36% (group B) of the MD patients reached the frequency band of 4 Hz, and 33% (group A) and 19% (group B) reached 5 Hz. The respective percentages for the controls were 97 and 77%. Of the 25 MD patients (group B) 72% had abnormal HART results. Among the group A of MD patients the HART (50%) was more sensitive to VOR abnormality than the caloric test (10%) was. For aggressively treated MD patients a decrease in gain at 2 and 3 Hz in the HART correlated with abnormal caloric test results. Increased body sway in posturography correlated with the pathological results in the HART. CONCLUSION: The HART is a complementary method for evaluating the natural frequency range of the VOR, and evaluation of MD patients may benefit from combined results of the caloric test and HART.

Changes in the vestibulo-ocular reflex: a study of elderly day hospital patients.

The vestibulo-ocular reflex (VOR) of 50 elderly day hospital patients (mean age of 82 years) was studied with the head autorotation test. Amplitude gain, phase and the highest frequency band reached were determined in the five frequency bands of 1, 2, 3, 4, and 5 Hz. Of the 50 patients, 81% had abnormal results. The gain of the elderly was significantly increased to 1.06-1.24 in the frequency bands of 3, 4, and 5 Hz in comparison with that of a control group. The elderly showed constantly a phase lead of 8-19 degrees in the frequency range of 1-4 hz and in this range differed significantly from the control group. The percentage of the elderly who reached high frequencies of head movements was reduced to 55% in the frequency band of 3 Hz and to 30% in the frequency band of 4 Hz. These findings may lead to oscillopsia and explain the high prevalence of dizziness and falls among the elderly.