Release of mediators of systemic inflammatory response syndrome in the course of a severe delayed hemolytic transfusion reaction caused by anti-D

Cells from primary porcine hepatocytes (PPH) and the immortalized human hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS). In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, because the cells come into direct or indirect contact with human blood components in BALSS, the effects of human complement on survival and functions of the cells was evaluated. For short-term culture, maintenance of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0.01). When cell viability was below 60% P450IA1 activity could not be recorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated with C3A viability (r = 0.896, p < 0.05). PPH metabolic function was superior to that of the C3A cell line when evaluated by P450IA1 activity, ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversible deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement. When sodium citrate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line. However, there was no demonstrable toxic effect when hepatic cells of either type were exposed to heparin. We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, and that heparin should be preferred for anticoagulation in BALSS.     

Favorable response to corticoid therapy in a patient with transverse myelitis in systemic lupus erythematosus

Transverse myelitis is one of the most unusual neurologic complications of systemic lupus erythematosus. Its pathogenetic mechanisms are controversial. Several therapeutic regimens have been attempted with contradictory results. Corticotherapy appears to improve prognosis, although some authors question its beneficial effects. The case of a patient with systemic lupus erythematosus and transverse myelitis, who presented a favourable clinical course following early treatment with high-dose corticoids, is reported.     

Development of severe secondary hypertension in a patient with systemic entomophthoromycosis

The sudden onset of hypertension mandates investigation for secondary causes. We report the case of a young man with a very rare systemic fungal disease that included massive unilateral perirenal adenopathy. Treatment was associated with the abrupt onset of severe hypertension. Imaging studies suggested progressive constriction of one kidney with treatment, presumably as a result of healing adenopathy. We suggest that this case is a new example of hypertension secondary to constrictive perinephritis (Page kidney).     

The effects of treatment with chemotherapy on energy metabolism and inflammatory mediators in small-cell lung carcinoma

A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (sICAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response.     

The effects of warfarin on calcinosis in a patient with systemic sclerosis

We describe the use of low doses of warfarin to treat calcinosis in a patient with systemic sclerosis or CREST syndrome. Our patient had Raynaud's phenomenon, skin sclerosis of the neck and the distal surface of the elbows, and pitting ulcers and scarification of the fingers as well as cutaneous calcinosis. After beginning warfarin, no calcium containing substance was discharged from the fingertip ulcers. There was no tendency to bleed and activated partial thromboplastin time and prothrombin time were normal. Sequential radiographs of the hands showed that calcinosis had improved. Since there seem to be few adverse effects, the use of warfarin in patients with calcinosis warrants further study.     

Relative contribution of endothelial cell and polymorphonuclear neutrophil activation in their interactions in systemic inflammatory response syndrome

OBJECTIVE: To examine the relative contribution of polymorphonuclear neutrophil (PMN) vs endothelial cell (EC) activation on the adherence and subsequent killing of ECs by PMNs. DESIGN: In vitro comparative studies of PMN-EC adherence and cytotoxicity. SETTING: Research laboratory and the surgical intensive care unit of a tertiary-level university hospital. PATIENTS: Patients with systemic inflammatory response syndrome admitted to the surgical intensive care unit and hospitalized preoperative noninfected surgical patients. INTERVENTION: None. METHODS: Polymorphonuclear neutrophils were isolated from 21 healthy volunteers, 22 preoperative patients, and 30 patients from the surgical intensive care unit with systemic inflammatory response syndrome. The PMNs were activated with lipopolysaccharide, 100 ng/mL (Escherichia coli 0111:b4), for 40 minutes at 37 degrees C before the adherence and cytotoxicity assays. Human umbilical vein endothelial monolayers were stimulated with tumor necrosis factor alpha, 25 ng/mL, and interleukin 1 beta, 15 U/mL, for 3 hours. The PMNs or EC cells were labeled with sodium chromate Cr 51 and used in a standard adherence or killing assay as required. RESULTS: Control and preoperative patient PMN treatment with lipopolysaccharide produced a modest increase in adherence. The PMNs from patients with systemic inflammatory response syndrome showed moderately increased human umbilical vein endothelial cell adherence, and this could not be augmented further with lipopolysaccharide stimulation. There was a marked increase in PMN adherence to EC after EC activation in all study groups (P < .001). Similar to the adherence data, human umbilical vein endothelial cell cytotoxicity was significantly increased in all groups after human umbilical vein endothelial cell activation (P < .01) but not after PMN stimulation with lipopolysaccharide. CONCLUSION: These data suggest that stimulation of ECs is far more important in producing increased adherence and cytotoxicity of EC than PMN stimulation with lipopolysaccharide in all study groups. Therapeutic efforts in patients with systemic inflammatory response syndrome should be focused on the EC.     

The relationship of packed cell transfusion to red blood cell deformability in systemic inflammatory response syndrome patients

Minor traumatic brain injury accounts for the majority of the one million head trauma attendances at A&E departments in the United Kingdom. Guidelines have been established listing criteria for skull films, admission to hospital, computed tomography, and neurosurgical consultation. These are currently undergoing revision and were the subject of a satellite symposium to the J Douglas Miller memorial meeting held in October 1996 in Edinburgh. In the East Anglia Region the current guidelines have been issued as memo-cards for A&E officers. The aim of admission is to observe for deterioration, predominantly caused by intracranial haematomas. The indicators for the development of such lesions are an impaired level of consciousness and presence of a skull fracture. Such patients should therefore undergo regular and frequent neurological observations, and be admitted for at least 12 hours. Following discharge, routine follow up should be considered to identify and treat patients with postconcussion symptoms and signs. The possible way forward for the management of these patients is adopting a greater emphasis on preventative aspects, and establishing, implementing, and auditing evidence based guidelines. Improved teaching in the form of formal induction seminars and computerised teaching aids is required, and a better understanding of the aetiology and treatment of the postconcussion syndrome.     

Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

BACKGROUND: Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B). METHODS AND RESULTS: Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001). CONCLUSIONS: Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.     

Local and systemic effects of macrophage cytokines in intestinal inflammation

The activation of macrophages and newly recruited monocytes appears to be common to both Crohn's disease and ulcerative colitis, despite different inductive stimuli. Similar activation occurs acutely during the course of invasive intestinal infections such as shigellosis, but is then usually downregulated. The macrophage cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1) are centrally involved in the local inflammatory response, and blockade of either cytokine greatly attenuates the inflammatory lesion. Induction of focal vascular thrombosis and matrix degradation are thought to be an important component of this focal damage. Both cytokines and IL-6 are now recognized to contribute to the systemic effects of intestinal disease, including growth suppression, anorexia, and chronic anemia. Disturbance of sleep patterns, mood, and affect may also occur, and recent evidence points towards bidirectional interplay between macrophage cytokines and central nervous system function.     

Azelastine reduces mediators of inflammation in patients with nasal polyps

Foot type and location of area of peak pressure under the metatarsal heads were determined for 54 healthy adults between the ages of 21 and 39 years. Feet were classified as neutral, pronated, or supinated. Each subject walked barefoot over a pedobarograph, and the area of peak pressure was identified as being either medial, central, or lateral under the metatarsal heads. A Fisher's exact test determined that there was a significant relationship between the area of peak pressure and foot type. A post hoc lambda asymmetric test showed that the relationship was very weak. Nearly half (49%) of the feet were classified as neutral, 36% were pronated, and 15% were supinated. Pressure patterns were as follows: 62% central, 26% medial, and 12% lateral. Other factors besides foot type influence the area of peak pressure under the metatarsal heads.     

Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis

OBJECTIVE: To compare the construct validity and sensitivity to change of 2 spondylitis-specific measures of functional disability, the Health Assessment Questionnaire Disability Index modified for the spondyloarthropathies (HAQ-S) and the Dougados Functional Index, with 2 more generic instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales-2 (AIMS2), in patients with ankylosing spondylitis (AS). METHODS: Construct validity was assessed in 2 ways: (1) by comparisons of the cross sectional correlations between each functional disability instrument and 6 measures of physical impairment in 216 patients, and (2) by relating changes over time in the HAQ-S and the Functional Index with changes in patient reported pain and stiffness in 153 patients followed for at least 2 years. Sensitivity to change was measured from the responses of 155 patients who reported a qualitative change in the activity of their AS during followup. RESULTS: Most patients had mild functional disability, with median scores of 0.5 on the HAQ-S (possible range 0-3), 0.375 on the HAQ (possible range 0-3), 11 on the Functional Index (possible range 0-40), and 5 on the AIMS2 (possible range 0-60). Scores on the HAQ-S (R2 = 0.24) and the unmodified HAQ (R2 = 0.18) were more highly correlated with measures of physical impairment than were scores on the AIMS2 (R2 = 0.10) or the Functional Index (R2 = 0.09). Changes over time in the HAQ-S and HAQ were more closely related to changes in pain and stiffness than were changes in the Functional Index. The HAQ-S and HAQ were also more sensitive to change than the Functional Index. CONCLUSION: The HAQ-S showed greater construct validity and sensitivity to change than the Functional Index, but performed similarly to the unmodified HAQ.     

Pulmonary infections associated with systemic capillary leak syndrome attacks in a patient with hypogammaglobulinemia

Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology, characterized by recurrent hypovolemic shock attacks associated in most cases with a serum monoclonal immunoglobulin. Prophylactic therapy is usually disappointing and the outcome is often fatal. We report on a patient with recurrent hypovolemic shocks consistent with the diagnosis of SCLS associated with severe serum panhypogammaglobulinemia but no detectable monoclonal immunoglobulin or B cell proliferation. Attacks were often preceded by severe respiratory infections. Both infections and attacks were successfully prevented by i.v. gammaglobulin replacement. Further evaluation is needed to assess the efficacy of i.v. gammaglobulins in patients with SCLS but without hypogammaglobulinemia.