The relationship of depression and stressors to immunological assays: a meta-analytic review.

This is a broad meta-analysis of the relations of both depression and stressors to immunological assays. The number of study samples (greater than 180) and measures (greater than 40) is much more extensive than any so far. Analyses are done by both fixed and random effects. By a fixed-effects analysis, both major depression and naturally occurring acute stressors are associated with (1) an overall leukocytosis, (2) mild reductions in absolute NK-cell counts and relative T-cell proportions, (3) marginal increases in CD4/CD8 ratios, and (4) moderate decreases in T- and NK-cell function. However, the degree of heterogeneity of the studies' results raises questions about their robustness. Therefore, we also did the first random effects analysis to estimate what is likely to appear in future studies. For depression, the analysis showed the immunological correlates included (1) an overall leukocytosis, manifesting as a relative neutrophilia and lymphoenia; (2) increased CD4/CD8 ratios; (3) increased circulating haptoglobin, PGE(2), and IL-6 levels; (4) reduced NK-cell cytotoxicity; and (5) reduced lymphocyte proliferative response to mitogen. For stressors, the random effects analysis showed that future studies are likely to find the following effects: (1) an overall leukocytosis, manifesting as an absolute lymphocytosis; (2) alterations in cytotoxic lymphocyte levels, CD4/CD8 ratios, and natural killer cell cytotoxicity with the direction of change depending on the chronicity of the stressor; (3) a relative reduction of T-cell levels; (3) increased EBV antibody titers; (4) reduced lymphocyte proliferative response and proportion of IL-2r bearing cells following mitogenic stimulation; and (5) increased leukocyte adhesiveness. The random-effects analysis revealed that for both major depression and naturally occurring stressors the following effects are shared: leukocytosis, increased CD4/CD8 ratios, reduced proliferative response to mitogen, and reduced NK cell cytotoxicity. The implications for these findings for disease susceptibility and the pathophysiology of these conditions is discussed.

Nutritional adaptation of women living with HIV: a pilot study.

The incidence of human immunodeficiency virus (HIV) infection in women worldwide is increasing rapidly. Assumptions about HIV-related immunologic and nutritional changes are primarily based on data derived from men infected with HIV. The article reports a pilot study designed to examine the immunologic and nutritional responses of a small group of women with HIV infection and to suggest the Roy adaptation model as a framework for understanding HIV-related changes in women. A cross-sectional descriptive design was used to study physiologic mode responses in women seropositive for HIV. Results indicated that the subjects had lower than normal total CD4+ counts. The mean body mass index and midarm muscle area of this cohort of women fell between the 50th and 75th percentiles, and the triceps skinfold thickness was slightly below the 50th percentile, compared with age-matched norms derived from NHANES II data. Although wasting and nutritional problems are common in men with HIV disease the results suggest that women at the midlevel of the disease may not yet have major problems with nutritional adaptation to HIV. Future studies using the Roy adaptation model with larger samples of women who are followed over time are needed to determine whether the decline in physiologic mode adaptation level noted in men infected with HIV is also experienced by women infected with HIV.

[Thumb reconstruction with free neurovascular wrap-around flap (bit-toe skin-nail flap) after traumatic amputation]. / Daumenrekonstruktion mit freiem, neurovaskulärem "Wrap-around"-Lappen (Big-toe Skin-Nail Flap) nach traumatischer Amputation.

From November 1993 until May 1995 there were three cases of traumatic loss of the thumb reconstructed, using the above mentioned method. In two cases, the thumbs were amputated in the region of the first phalanx, in one case in the region of the metacarpophalangeal joint. Thumb reconstruction in the technique described by Morrison et al. (1980) involved the neurovascular wrap-around flap from the ipsilateral greater toe. The flap consisted of 4/5 of the soft-tissue including the nail of the big toe and parts of the distal phalanx as well as the fibular nerve of the toe. The vessels of the flap included the first dorsal metatarsal artery and two branches of the vena saphena magna. This paper details surgical technique, pointing out its advantages and disadvantages and compares it with other procedures.

Experiences of African American and Caucasian women who survive urban residential fires.

This study examined differences in socioeconomic characteristics, traumatic experiences suffered, and psychological distress in African American and Caucasian women 3 months after urban residential fires. Distress was measured by the Brief Symptom Inventory (BSI). The sample included 310 women (224 African Americans and 86 Caucasians). The African American women had lower levels of education and income than the Caucasian women, and were more likely to be unmarried. Injury and deaths of loved ones were similar in the two groups; African American women reported greater loss of possessions, less insurance coverage, and less displacement than Caucasian women. African American and Caucasian women scored similarly on the BSI. Scores on the BSI for both groups were higher than the norms reported in the literature.

Natural killer cells over time in patients with colorectal cancer.

PURPOSE: The purposes of the investigation were: 1) to examine the natural killer (NK) cell levels in a homogeneous group of patients with cancer between the presurgical period and 6 months after surgery; 2) to identify changes in the number of NK cells over time; and 3) to determine whether an association exists among the number of NK cells, demographics, stage of cancer, and treatment variables. DESCRIPTION OF STUDY: A longitudinal descriptive design was used to study biopsychosocial factors in persons newly diagnosed with colorectal cancer over a 6-month period. RESULTS: Patients without ostomies had a significant decrease in NK levels over time, whereas patients with ostomies had a significant increase in NK levels over time. There was a difference in NK level over time for patients who were receiving the additional therapy of radiation alone and a combination of radiation and chemotherapy from those patients who were not receiving additional therapy. Natural killer levels in patients who were receiving radiation alone or a combination of radiation and chemotherapy significantly declined over time, where NK levels in patients receiving no additional treatment significantly increased over time. CLINICAL IMPLICATIONS: Patients with low NK levels should be monitored during the course of their illness and cancer treatment to determine the relationship to immune status of other variables such as nutritional status, infection rates, and functional status.

Backward and forward walking use different patterns of phase-dependent modulation of cutaneous reflexes in humans.

1. The phase-dependent modulation of medium-latency (P2) (70-80 ms) responses in semitendinosus (ST), biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) was studied with the use of low-intensity stimulation (2 times perception threshold) of the sural nerve. The shocks were given in a random order at 16 phases of the step cycle in 10 normal subjects during forward walking (FW) or backward walking (BW) on a treadmill. 2. All subjects exhibited P2 responses in all muscles studied both during BW and FW. The amplitude of the facilitatory P2 responses showed phase-dependent changes that could not have been predicted on the basis of the variations in background activity throughout the step cycle. 3. During FW, the P2 facilitatory responses in BF were large (with respect to the background activity) throughout the whole step cycle except for a short period near the end of the swing phase. In ST the responses were smaller and appeared primarily at the end of the stance phase and during the first part of the swing phase. During the second half of swing the P2 responses were basically suppressive. A modulation pattern similar to the one in ST was found in RF and TA, except that there was no reversal to suppressive responses in the swing phase in RF. Instead, a reduction in the amplitude of the facilitatory P2 responses occurred. 4. During BW, the modulation pattern recorded in the same subjects was different from the one seen during FW. Large facilitatory P2 responses were present in all muscles in middle and late swing. In the first half of stance the responses were most prominently seen in BF and RF. At the end of stance and/or at the onset of swing the facilitatory responses decreased in amplitude (BF and RF) or reversed to P2 suppressions (ST and TA). 5. We conclude that there are both facilitatory and suppressive pathways from the sural nerve to the leg muscles studied and that the balance of activity in these paths is phase dependent during both FW and BW. It is suggested that the phase-dependent modulation of P2 responses could largely rely on a central motor program. During BW the same motor program is used as during FW, but possibly running in reverse, thereby causing a shift both in the timing of the reflex reversal and in the periods of reflex suppression.

Bipedal reflex coordination to tactile stimulation of the sural nerve during human running.

1. Cutaneous reflex responses were elicited during human running (8 km/h) on a treadmill by electrical stimulation of the sural nerve at the ankle. Stimulus trains (5 pulses of 1 ms at 200 Hz) at three nonnociceptive intensities, which were 1.5, 2.0, and 2.5 times perception threshold (PT), were delivered at 16 phases of the step cycle. For 11 subjects the surface electromyographic (EMG) activity of both the ipsilateral and contralateral long head of the biceps femoris (iBF and cBF, respectively), the semitendinosus (iST and cST), the rectus femoris (iRF and cRF), and the tibialis anterior (iTA and cTA) were recorded. 2. During human running nonnociceptive sural nerve stimulation appears to be sufficient to elicit large, widespread and statistically significant reflex responses, with a latency of approximately 80 ms and a duration of approximately 30 ms. These reflex responses seem to be an elementary property of human locomotion. This is indicated by the occurrence of the responses in all subjects, the consistency of most of the reflex patterns across the subjects and, apart from a small amount of habituation, the reproducibility of the responses during the course of the experiment. 3. The responses are modulated continuously throughout the step cycle such that their magnitude does not in general covary with the background locomotor activities. This is observed most clearly in iST, iTA, and cTA for which statistically significant reflex reversals are demonstrated, and in cRF and cTA for which the responses are gated during most of the step cycle. 4. The response magnitude generally increases as a function of increasing intensity, whereas the phase-dependent reflex modulation is intensity independent. 5. A functional dissociation within the ipsilateral hamstring muscles is demonstrated: the iBF and iST show an antagonistic reflex pattern (facilitatory and suppressive, respectively) during the periods of synergistic background locomotor activity in the step cycle. Contralaterally, however, the cBF and cST are reflexively activated as close synergists during these periods. 6. The reflex responses and their phase-dependent modulation are different for the homologous muscles in the two legs. Yet, some similarities are observed. These are present rather with respect to the phase of the corresponding leg than with respect to the phase of the stimulated leg. Both observations suggest that the phase-dependent reflex modulation is controlled separately in the ipsilateral and contralateral legs. 7. The response simultaneity in all investigated muscles supports the notion of a coordinated cutaneous interlimb reflex during human running.(ABSTRACT TRUNCATED AT 400 WORDS)

Gating of sensation and evoked potentials following foot stimulation during human gait.

To investigate how gait influences the perceived intensity of cutaneous input from the skin of the foot, the tibial or sural nerves were stimulated at the ankle during walking or running on a treadmill. As compared to standing, the detection threshold for these stimuli was raised by more than 30% during the locomotion tasks. During walking, there was a phase-dependent modulation in perceived intensity of suprathreshold stimuli (1.5, 2, or 2.5 x PT). Stimuli given just prior to footfall were perceived as significantly above average (Wilcoxon signed-rank test). In contrast there was a significant phasic decrease in sensitivity for shocks delivered immediately after ipsi- and contralateral footfall. The amplitude of somatosensory evoked potentials (P50-N80 complex), simultaneously evoked from pulse trains to the sural nerve and recorded at scalp level, was, on average, 62% of the level during standing. During gait, the amplitude of this complex was significantly smaller just after footfall than the amplitude during late swing (MANOVA). It is suggested that the reduced sensation and the decreased evoked potentials after touchdown may be due to occlusion or masking by concomitant afferent input from the feet. On the other hand, the phasic increase in sensitivity at the end of swing is thought to result from a centrally generated facilitation of sensory transmission of signals in anticipation of foot-placing.

A descriptive study of immune status in patients undergoing colorectal surgery: lymphocyte phenotypes.

PURPOSE/OBJECTIVES: To describe immune status in patients prior to colorectal surgery for cancer, to establish values to serve as a baseline for subsequent analyses, and to describe a procedure for studying phenotypes of the immune system, elucidating its advantages. DESIGN: One component of a larger longitudinal survey. SETTING: Two large, inner-city university hospitals and two of their affiliated hospitals in the northeastern United States. SAMPLE: Patients undergoing surgery for colorectal cancer (N = 94). Subjects were primarily male (n = 57) and Caucasian (n = 85) and ranged in age from 26-88 years (mean = 63). Seventy-seven percent (n = 73) had cancer, 23% (n = 21) had benign diseases or conditions. METHODS: Flow cytometry analysis of lymphocyte phenotypes was performed on blood samples drawn from patients before they underwent surgery for colorectal cancer. MAIN OUTCOME MEASURES: The average absolute lymphocyte subset levels and the average relative lymphocyte subset levels of blood samples taken from patients undergoing surgery for colorectal cancer were compared (using t-tests) with the subset levels of two normal reference samples. FINDINGS: The average absolute lymphocyte subset levels and average relative lymphocyte subset levels of patients undergoing surgery for colorectal cancer fell within normal ranges. CONCLUSIONS: These findings suggest that this sample of patients undergoing surgery has one essential element of an intact immune system--normal levels of lymphocyte subsets. IMPLICATIONS FOR NURSING PRACTICE: There is no indication preoperatively that this population is at a higher risk for infection or delayed wound healing. However, there may be other times in the illness trajectory when the immune system does become compromised, and these values prior to surgery will serve as a baseline to identify changes in patients' immune status over time. Further longitudinal studies are necessary.

Increased amplitude of cutaneous reflexes during human running as compared to standing.

The amplitude of H-reflexes is decreased during walking as compared to standing and a further reduction is seen during running as compared to walking. Does a similar reduction occur for reflexes elicited by cutaneous stimulation? To answer this question, the electromyographic (EMG) responses in biceps femoris (BF) and tibialis anterior (TA) to a 20 ms train of 5 electrical pulses, were recorded. This stimulus was applied to the sural nerve at the ankle, either at 16 different phases of the step cycle in human volunteers running on a treadmill at 8 km/h or at different isometric contraction levels of TA and BF in the same subjects during standing, imitating the postures of different phases of the step cycle. The mean latency of the main responses in BF of all subjects was 76 ms. Similar responses (P2), with a latency of 79 ms were seen in TA in 6 of the 10 subjects. For a constant strength of stimulation (2 times perception threshold) during isometric contractions at different levels in early stance imitation, the mean reflex ratio's (reflex/background) of BF and TA responses were 1.07 and 0.53, respectively, while the ratio's for these 2 muscles during running were 1.78 and 1.1. The higher reflex ratio's in running were primarily due to the large facilitatory responses, which were present during most of the step cycle but rarely during voluntary contractions in the subjects during standing. At the end of the swing phase, however, the responses in BF and TA were predominantly suppressive, as were most of the responses to stimulation applied to the standing subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

New aspects of human muscle coordination as revealed by motor-unit studies.

Increasing evidence has become available against the view that individual muscles should be regarded as functional units in the control of force by the motor apparatus. The relative contribution of various motoneurone pools (belonging to a single muscle) to muscle force appears to depend on the direction of torque exerted by the corresponding limb. This clearly indicates the presence of more than one control or activation parameter for the total motoneurone pool of a single muscle. Windhorst et al. (1989) have even proposed a combined sensory and neuromuscular partitioning, such that segmental control mechanisms are based on subdivisions of motoneurone pool--muscle complexes. Size-related recruitment occurs within these subdivisions rather than in the motoneurone pool as a whole. Moreover, motoneurones can operate in various modes (different relative contributions of the recruitment mechanism and the firing frequency mechanism to muscle force) related either to movement or to force. This indicates that muscle coordination is organised differently in force tasks and in movement tasks. These properties of motoneurone activation mentioned above are difficult to incorporate in existing models on sensorimotor organisation. Some of these discrepancies will be reviewed in order to highlight future directions for modelling.

Phase-dependent reversal of reflexly induced movements during human gait.

To investigate whether phase-dependent reversals in reflex responses on electromyography (EMG) are accompanied by movement reversals, a series of human volunteers were studied for their behavioural responses to sural nerve stimulation during running or walking on a treadmill. Low-intensity stimulation (less than 2.5 x perception threshold, T) of the sural nerve yielded facilitatory responses in the tibialis anterior muscle (TA), correlated with an induced ankle dorsiflexion (mean maximum 4 degrees) in early swing. The same stimuli yielded primarily TA suppression and weak ankle plantar flexion (mean maximum 1 degree) at end swing. The correlated induced knee angle changes did not precede the ankle changes, and they were relatively small. Mean maximum flexion in early swing was 6.2 degrees, while mean maximum extension was 3.7 degrees. High-intensity stimulation of the sural nerve (greater than 2.5 x T) always gave rise to suppression of the ongoing activity. This resulted in a second type of movement reversal. During late stance and early swing the responses in TA were suppressive (i.e. below background activity) and related to ankle plantar flexion. In contrast, the responses during early and middle stance consisted of suppression in extensor activity (gastrocnemius medialis and soleus) and ankle dorsiflexion. The data are discussed in terms of a new hypothesis, which states that the responses to electrical stimulation of cutaneous nerves during locomotion do not correspond directly to corrections for stumbling following mechanical perturbations during the step cycle. Instead, the data invite a reinterpretation in terms of the opening and closing of reflex pathways, presumably by a central pattern generator for locomotion.

A model for neural control of gradation of muscle force.

A mathematical muscle model is presented that relates neural control signals linearly to muscle force without violating important known physiological constraints, such as the size-principle (Henneman and Mendell 1981) and non-linear twitch summation (Burke et al. 1976). This linearity implies that the neural control signals (defined as a weighted sum of activities in a nerve bundle) can be interpreted as the internal representation of total muscle force. The model allows for different relative contributions from the two force-grading mechanisms, i.e. the recruitment of motor units and the modulation of their firing frequency. It can therefore be applied to a variety of (distal and proximal) muscles. Furthermore, it permits simple mechanisms for controlling muscle force, e.g. in superposed motor tasks. The model confirms our intuitive notion that a weighted sum of activities in a nerve bundle can directly represent an external controlled variable, which in this case is exerted muscle force.

Selective activation of human soleus or gastrocnemius in reflex responses during walking and running.

Phase-dependent reflex modulation was studied by recording the electromyographic (EMG) responses in soleus (SOL) and gastrocnemius medialis (GM) to a 20 ms train of 5 electrical pulses, applied to the sural or tibial nerve at the ankle, in 14 volunteers walking or running on a treadmill. Although both the spontaneous activity and the reflex responses were usually similar for both muscles, instances were identified in which separate control was evident. During walking (4 km/h), activity in SOL started earlier in the stance phase than GM activity. Correspondingly, the amplitude of the reflex responses was larger in SOL than in GM in early stance, both ipsi- and contralateral to the side of stimulation. In some cases, the same stimulus could elicit contralaterally a suppression of GM in synchrony with a facilitation of SOL. These crossed extensor reflexes had a low threshold (1.2 x T) and a latency ranging from 72 to 105 ms. During running (8 km/h or more), responses were seen selectively in GM instead, without concomitant responses in SOL. Such responses had a latency ranging from 82 to 158 ms and they appeared during the first extension phase, at the end of the swing phase. In addition, selective GM responses, with latencies above 200 ms, were seen near the transition from stance to swing during running. These instances of separate reflex control of SOL and GM were correlated with step cycle periods during which the motoneurones of either one of these muscles received more spontaneous activation than the other. Nevertheless, it is argued that premotoneuronal gating must also be involved since the increased amplitude of the crossed SOL responses (in early stance) and of GM responses (at end swing) was not strictly linked to an elevated amount of spontaneous activity during these parts of the step cycle as compared to other parts.

Differences in coordination of elbow flexor muscles in force tasks and in movement tasks.

Motor-unit activity in m. biceps brachii, m. brachialis and m. brachioradialis during isometric contractions has been compared with motor-unit activity during slow voluntary (extension and flexion) movements made against external loads. During these slow movements the recruitment threshold of m. biceps motor units is considerably lower than it is during isometric contractions but the recruitment threshold of both m. brachialis and m. brachioradialis motor units is considerably higher. For all three elbow flexor muscles the motor-unit firing frequency seems to depend on the direction of movement: the firing frequency is higher during flexion movements (3 deg/s) and lower during extension movements (-3 deg/s) than during isometric contractions. The relative contribution of the biceps to the total exerted flexion torque during slow voluntary movements is estimated to increase from 36% to about 48% and that of the brachialis/brachioradialis is estimated to decrease from 57% to about 45% compared to the relative contribution of these muscles during isometric contractions. This difference in the relative contribution of the three major elbow flexor muscles is shown to be caused by differences in the central activation in force tasks and movement tasks.

Differences in central control of m. biceps brachii in movement tasks and force tasks.

Motor-unit activity in m. biceps brachii during isometric flexion contractions has been compared with motor-unit activity during a) slow voluntary movements against constant or increasing preloads and b) flexion contractions while movements were imposed by a torque motor. Recruitment levels and firing frequency behaviour of the motor units were found to be very similar when torques were generated during isometric contractions and during the imposed movements. However, these characteristics of the biceps motor units were quite different during the slow voluntary movements. It is suggested that the central activation of the alpha and/or gamma motoneurone pools of m. biceps brachii is different for force tasks and slow movement tasks, even if the same torques are exerted and/or movements are made.

Differences in the activation of m. biceps brachii in the control of slow isotonic movements and isometric contractions.

We have compared muscle activation in the control of slow isotonic movements and isometric contractions. Specific attention has been given to the contribution of the two force-grading mechanisms, the recruitment of motor units and the modulation of firing frequency in motor units that have already been recruited. The recruitment order of the m. biceps motor units under study was the same during isometric contractions and slow isotonic movements. However, the recruitment thresholds of the m. biceps units were considerably lower for both isotonic flexion and extension movements, even at velocities as low as 2 deg/s, than for isometric contractions. Furthermore, firing frequency at recruitment was found to depend on the motor task: at recruitment the motoneurone starts firing with a higher firing frequency during isotonic flexion movements and a lower firing frequency during isotonic extension movements than during isometric contractions. Two main conclusions can be drawn from these results. First of all, the concept of one single activation parameter (total synaptic drive?) cannot account for the motor-unit behaviour observed during our experiments: the relative contribution of the two force-grading mechanisms is different for different tasks. Secondly, the distribution of activity among flexor motoneurone pools is different for isometric contractions and isotonic movements.

Collicular ensemble coding of saccades based on vector summation.

The superior colliculus in the monkey contains a topographically organized representation of the target in its upper layers and saccade-related activity in its deeper layers. Since collicular movement fields are quite large, a considerable region of the colliculus is active whenever a saccade is made. We have modelled the collicular role in saccade generation based on the idea, proposed earlier in the literature, that each movement cell causes a movement tendency in the direction of the external world point which it represents in the collicular map. The model is organized as follows: An anisotropic logarithmic mapping transforms retinal coordinates into collicular coordinates. A two-dimensional Gaussian function describes the spatial extent of the movement-related activity in the deeper layers. An efferent mapping function specifies how the direction and the size of the movement contribution of each colliculus neuron depends on its location and its firing rate. The total saccade is the vector sum of the individual cell contributions. This very simple model (seven fixed parameters) has been used to simulate metrical properties of saccades: in response to visual targets; in response to electrical stimulation in one colliculus, and after a colliculus lesion. Model performance appears to be remarkably realistic but cannot account for some border effects and responses to double stimulation. Suggestions on how the model can be improved and extended will be presented.

A subset of normal human B lymphocytes expresses an antigen cross-reactive with gp52 of murine mammary tumor virus.

Three monoclonal antibodies (MAbs), VE7, VIG3, and IXF9, that detect the 52-kd glycoprotein (gp52) of murine mammary tumor virus (MMTV) were tested for reactivity on normal human tonsillar lymphoid cells in an indirect immunofluorescence assay. Two of the MAbs, VE7 and VIG3, reacted with subpopulations of B cells, whereas the third MAb, IXF9, showed only very low-level reactivity with human lymphoid cells. VE7 and VIG3 also reacted with small populations of peripheral blood lymphocytes, and all three MAbs reacted with some transformed human cell lines. The data suggest that subpopulations of normal human lymphocytes express antigens that are cross-reactive with the MMTV gp52, although not all of the viral gp52 epitopes are expressed on the surface of these cells.