Role of phosphoinositide 3-kinase in TCR-signaled regulation of CD8-mediated adhesion to class I MHC protein.

CD8 must be activated by signaling through the TCR in order to mediate CTL adhesion. Up-regulation of adhesion to class I protein is shown to be blocked by specific inhibitors of phosphoinositide 3-OH kinase (PI3-K), indicating a critical role for this enzyme in signaling for activation of CD8. A minimal TCR stimulus that activates CD8 does not result in a detectable increase in total cellular PI3-K activity, but an increase in PI3-K activity associated with p59(fyn) kinase can be detected. Genistein blocks this increase concomitantly with blocking the activation of adhesion, suggesting that activation of fyn-associated PI3-K is downstream of TCR-dependent activation of protein tyrosine kinase(s) in the signaling pathway that leads to up-regulation of CD8-dependent adhesion. Treatment of cells with phorbol ester also blocks the TCR-dependent increase in fyn-associated PI3-K and inhibits CD8-dependent adhesion. This suggests a feedback model for deactivation of CD8 adhesion to allow target cell release by CTL and recycling to kill additional targets. In contrast, phorbol ester treatment up-regulates integrin-mediated adhesions, suggesting complex cross-talk between the TCR and the different adhesion/cosignaling receptors during the binding and killing of antigen-bearing targets.

Workplace assessment: a tool for occupational health and safety management in small firms?

This paper discusses the capability of small firms to comply with legislative demands on risk assessment. The results of a national survey show that only a minor fraction of small firms comply. Two case studies demonstrate that small firms are able to meet the demands. An analysis of these cases leads to some hypotheses on the preconditions for compliance. Many firms need a person to mediate legislative demands. The demands for qualifications to fulfil this role are discussed. The conclusion is that it is possible to qualify persons as mediators. Therefore, to stimulate ergonomic activities in small firms resources for such mediators are required. The occupational health services are able to train a staff to undertake the task.

Rapid adjustment of antihypertensive drugs produces a durable improvement in blood pressure.

Antihypertensive drugs are often initiated and adjusted over a period of weeks to months. It is not clear whether the time and inconvenience of this approach is necessary. We studied whether or not drug adjustment over several days in the context of a physician-nurse team could produce a durable blood pressure benefit according to home blood pressure measurements. Sixty-eight patients (aged 65 +/- 1 years, 47% men) were referred for management of hypertension. Indications for referral were new hypertension (13%), known/controlled hypertension (30%), or known/uncontrolled hypertension (57%). Patients had one to three brief nurse visits/day and were provided with an accurate semiautomated device for self-blood pressure (BP) measurement. Sixty patients provided follow-up data. Group 1 (n = 16) required no change in their preexisting drug regimen during clinic visits, whereas group 2 (n = 44) had drug therapy initiated or adjusted over 4 +/- 1 days. Patients were evaluated at baseline, at dismissal from the clinic, and at latest follow-up (mailed-in report of 42 readings taken over 7 days at 1- to 3-month intervals). Mean follow-up was 11 +/- 0.5 months. Mean BP at baseline, dismissal, and latest follow-up for group 1 were 132 +/- 4/73 +/- 2, 130 +/- 6/70 +/- 2, and 125 +/- 3/73 +/- 3 mm Hg (P = not significant). Mean BP for group 2 at the same intervals were 150 +/- 4/80 +/- 2, 139 +/- 3 (P < .01 v baseline)/75 +/- 2, 133 +/- 2 (P < .01 v baseline and < .05 v dismissal)/74 +/- 1 (P < .01 v baseline). The BP control rate (blood pressures less than 140/90 mm Hg) was 75% in group 2. Drug number/dose remained the same or lower in 87% and 91% of patients during follow-up in groups 1 and 2, respectively. These results suggest that a clinically significant lowering of blood pressure can often be achieved over several days and maintained for up to 1 year. Increased use of rapid drug titration, a physician-nurse team approach, and self-BP measurement at prescribed intervals have the potential to improve BP control rates and reduce the expense and inconvenience associated with the treatment of hypertension.

Are aneroid sphygmomanometers accurate in hospital and clinic settings?

BACKGROUND: The aneroid sphygmomanometer is commonly used for the indirect measurement of blood pressure despite significant concerns about its accuracy. Although the mercury sphygmomanometer is highly accurate, there are concerns about the environmental toxicity of mercury. In response to various external pressures to become essentially mercury free, the Mayo Clinic, Rochester, Minn, has replaced many mercury sphygmomanometers with aneroid devices. Since 1993, a maintenance protocol has been in place to ensure proper function and accuracy of these devices. METHODS: We assessed the accuracy of 283 aneroid devices using as the reference standard a digital pressure and vacuum meter that was calibrated using a mercury sphygmomanometer. RESULTS: The mean +/- SD values from the aneroid device in millimeters of mercury at each reference point (at 20-mm Hg intervals from 60 to 240 mm Hg defined by the reference device) were 59.9 +/- 1.9 at 60; 79.9 +/- 1.9 at 80; 100.0 +/- 1.8 at 100; 120.3 +/- 1.8 at 120; 140.7 +/- 1.4 at 140; 160.7 +/- 1.7 at 160; 180.9 +/- 1.3 at 180; 200.7 +/- 5.0 at 200; 221.0 +/- 1.3 at 220; and 240.8 +/- 1.6 at 240 (r = 0.99; P<.001). The values from the aneroid device underestimated those of the reference device by a mean of 0.5 mm Hg (95% confidence interval, 0.3-0.7). Virtually 100% of the values from the aneroid device were within the 4-mm Hg range recommended by the Association for the Advancement of Medical Instrumentation. CONCLUSION: Aneroid sphygmomanometers provide accurate pressure measurements when a proper maintenance protocol is followed.

Activation of antigen-specific T cells by artificial cell constructs having immobilized multimeric peptide-class I complexes and recombinant B7-Fc proteins.

T cell activation results from the engagement of multiple receptors on T cells by their respective ligands on antigen presenting cells. Studies using artificial cell surface constructs have demonstrated that effective T cell response requires that antigen be presented on a solid surface with dimensions that approximate those of an intact cell. In this report, we describe the cloning and expression of recombinant B7-1-Fc and B7-2-Fc proteins and their incorporation onto 5-microm latex microspheres along with renatured peptide-MHC. These microspheres provide a simple and effective method for the in vitro or in vivo stimulation of antigen-specific T cells under precisely controlled antigen and costimulation conditions.

Development and evaluation of a two-dimensional electrocutaneous cognitive feedback system for use in paraplegic standing.

Fatigue of electrically activated paralysed muscles is a major factor limiting the duration of functional electrical stimulation (FES) supported paraplegic standing. Fatigue can be significantly delayed by changing the posture. Since paralysed individuals are deprived of proprio- and exteroception from the lower limbs they are not aware of the posture and loading of their paralysed legs. If suitable cognitive feedback (CF) information about posture in the sagittal and frontal planes is provided, they might be able to successfully exercise posture switching. A two-dimensional electrocutaneous CF system was developed. Relative limb loading and the location of the weighted centre of pressure were selected as informational variables. Discrete encoding schemes in the form of spatial and frequency codes were employed and the informational signals were divided into three sub-regions. The ability to correctly interpret the CF was investigated using one- and two-dimension tracking tests in three paralysed subjects, each of whom were studied over five consecutive days. All three subjects were able to use the CF in one-dimension tests. Two subjects could do the same also in two-dimension tests. The encoding scheme which was developed to communicate the selected biomechanical variables proved to be easily understood and thus appropriate for use in paraplegic standing.

Spiral fracture fixation techniques. A biomechanical study.

The mechanical strengths of five common fixation techniques for spiral fractures have been tested. A total of 240 cadaver metacarpals and proximal phalanges were fractured and fixed by either crossed K-wires, interosseous loops, a dorsal mini-plate, a single compression screw or K-wire plus cerclage wire. Specimens were subjected to torsional and cantilever bending tests. A single compression screw provided the best overall fixation for the proximal phalanx. In addition, a single compression screw provided better fixation than any of the other techniques when proximal phalanges and metacarpals were subjected to torsional tests (P < 0.05). In apex dorsal bending tests of metacarpals, the screw provided fixation superior to interosseous wires, crossed K-wires, or dorsal mini-plates (P < 0.05). These results indicate that the use of a single compression screw provides the most satisfactory biomechanical advantage for spiral fracture fixation.

Adventitial cystic disease of the lesser saphenous vein.

Adventitial cystic disease or degeneration of the blood vessel wall is an unusual form of peripheral vascular disease that occurs almost exclusively in the popliteal artery and accounts for an estimated one in 1200 cases of claudication. The cause of adventitial cystic disease is unknown, but it has been attributed to repeated trauma, an ectopic ganglion, or primary dysplasia of the vascular connective tissue. We describe an unusual case of adventitial cystic disease of the lesser saphenous vein located adjacent to the ankle joint. Only a handful of cases of venous adventitial cystic disease have been reported in the English literature, and, to our knowledge, none involved the lesser saphenous vein.

Use of a portable floor crane as an aid to resection of the massive panniculus.

Resection of the massive abdominal panniculus is technically difficult due to the weight of the tissue and the difficulty in controlling the tissue during surgery. The authors describe the use of a portable floor crane that facilitates resection by reducing the number of assistants required, increasing exposure, and providing for adequate control of the specimen, which assures proper preoperative markings and sterile preparation. Blood loss is reduced, as is operating time. The portable floor crane is usually available in hospital maintenance departments and can be easily modified for intraoperative use.

Moderate cold exposure in the Faroe fishing industry.

Differences in female workers' finger temperatures, manual dexterity, ratings on thermal comfort, and local cooling exposure were studied in three factories in the Faroe Island fishing industry. Environmental temperatures in the factories varied from 5 to 19 degrees C with vertical gradients of 7 degrees C/m, and the mean temperatures of the flushing water varied from 2 to 15 degrees C. Finger temperature varied from 12 to 24 degrees C when measured 2 min after work was stopped, and about one-third of the women experienced thermal discomfort in the fingers during work. The fish temperature increased, on the average, less than 1 degrees C during passage through the production room, notwithstanding the thermal differences among the factories. These findings should be used in attempts to reduce the cold exposure of the workers; but also improved control should be recommended for both environmental and water temperatures in the factories.

[Subcutaneous emphysema caused by anastomotic leakage]. / Subkutant emfysem ved anastomosebrist.

A case of subcutaneous emphysema with pneumoperitoneum/mediastinum caused by anastomic leakage is reported.

Induced rhinovirus infection under controlled exposure to sulfur dioxide.

The interaction between short-term sulfur dioxide (SO2) exposure and experimentally induced rhinovirus infection was studied in thirty-two volunteers divided into two groups balanced with respect to age, antibody levels, and nasal mucus flow rates. One group was exposed to SO2 exposure at the threshold limit value (TLV) of 5 ppm during 4 hours; the other group served as controls exposed to pollution-free air under the same conditions. The SO2 exposure caused a 50% decrease in nasal mucus flow rate in the anterior parts of the nose, but there was no difference in the number of colds which developed in the two groups. The group exposed to SO2 had fewer symptoms and a possibly shorter incubation period (P = .06), and virus shedding was at a lower level but more persistent than in the control group. No differences were found in antibody response. The rhinovirus infection in the control group caused a gradual decrease in nasal mucus flow rate starting 2 days after the virus instillation, and after 5 days the rate was less than half its initial value. For future experiments on the interaction between airborne pollutants and rhinovirus infections, a virus challenge by aerosol inhalation is recommended. Our study supports an earlier observation that growth of influenza virus in the nasal cavity of mice was inhibited by exposure to SO2 concentrations of 6 or 20 ppm.

The effects of moderate heat stress on patients with ischemic heart disease.

With the use of a climate chamber, the effects of a 3-h exposure to moderate heat stress (23 to 29 degrees C) on the physiology, comfort, and performance of 20 subjects, 10 with slight (group I) and 10 with moderate (group II) ischemic heart disease (IHD), were studied. Twenty matched control subjects were similarly exposed. All of the subjects performed sedentary, mental work throughout the exposure. Humidity was 9 mm Hg; air velocity, 10+/-3 cm per second; and thermal resistance of the clothing, 0.7 clo. Under identical conditions no significant differences in rectal, skin, and finger temperatures or weight loss existed between the three groups, but during heat stress the temperatures and weight loss were always significantly higher than under the control conditions, except for rectal temperatures during the first 2 h. There was no difference between the groups or the two sets of conditions in respiration rate and diastolic blood pressure, but the patients had a significantly lower systolic blood pressure in the third hour of heat stress than under the control conditions. Heart rate and the rate-pressure-product during heat stress were significantly higher in the controls than in the patients. A few patients experienced a slight retrosternal oppression during heat stress, but only one had ECG changes, and none of these symptoms or signs were present under control conditions. Under both sets of temperature conditions the patients were uncomfortable during a longer period of time than the controls, and they were more sensitive to temperature changes, group II being more sensitive than group I. The comfort distribution curve was very narrow for group II. The performance tests were numerical addition, card punching, cue-utilization and creative association. In numerical addition no temperature effect could be shown on the speed of working, but for the patients in group II during heat stress the level of accuracy in the second hour was lower than under control conditions; the trend was the opposite for control subjects. No differences occurred in the first or third hour. In card punching the patients in group II worked significantly more slowly during heat stress than did the control subjects, who improved their performance in heat, as did the paracy with which this task was performed, the patients in group II making significantly more errors in the heat than patients in group I. Cue-utilization did not differ between groups or conditions. Patients performing the creative association test under heat stress supplied significantly fewer unique answers than did patients working under control conditions; no such effect of heat was observed for control subjects. We conclude that patients with IHD are more sensitive to moderate heat stress than healthy control subjects in terms of mental performance and comfort. There are some differences in cardiopulmonary function but no differences in thermoregulation.