The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.     

Time-dependent differential changes of immune function in rats exposed to chronic intermittent noise

Noise is a highly relevant environmental and clinical stressor. Compared to most other experimental stressors, noise is a modest activator of neuroendocrine pathways that mimic the situation in human health where neuroendocrine activation by environmental stressors is often absent or difficult to establish. Little is known about the effects of noise exposure on the immune system. In the present work, the effects of a low-intensity chronic intermittent unpredictable noise regimen on various parameters of immune function was studied. Male wistar rats were exposed to a randomized noise protocol (white noise, 85 dB, 2-20 kHz) for 10 h per day, 15 min per h over a total period of 3 weeks. Control animals were exposed to ambient sound only. Immune function was monitored after 24 h, 7 days, and 21 days of noise exposure. Noise induced several significant changes in immune function in a time-dependent differential pattern involving both immunosuppression and immunoenhancement. After 24 h, serum IgM levels were increased and peripheral phagocytic activity was decreased. Splenic lymphocytic proliferation to mitogens was significantly decreased after 7 days, but slightly elevated after 3 weeks. The activity of splenic NK cells was increased significantly after 24 h and 7 days, but suppressed after 3 weeks. These results show that various parameters of immune function are affected differentially over time in a period of chronic mild noise stress, possibly due to sequential activation of different physiological mechanisms.     

Reversible parotid enlargement and pseudo-Sj?gren's syndrome secondary to hypertriglyceridemia

We describe 2 patients with a Sj?gren-like syndrome apparently secondary to hypertriglyceridemia. Both had bilateral parotitis in addition to musculoskeletal and sicca symptoms. Parotid gland histology revealed fatty infiltration with no inflammation. Therapy with dietary modification and triglyceride lowering drugs resulted in resolution of symptoms and parotid swelling in one patient. In the 2nd patient, hypertriglyceridemia was resistant to triglyceride lowering drugs, and parotid symptoms and swelling continued unabated. Our findings suggest aggressive treatment of hyperlipidemia in pseudo-Sj?gren's syndrome may result in amelioration of musculoskeletal and parotid symptoms.     

Dual recognition of lipid A and DNA by human antibodies encoded by the VH4-21 gene: a possible link between infection and lupus

The VH4-21 (V4-34) gene segment, a member of the VH4 family, is expressed early in B-cell maturation and is utilized by approximately 6% of normal adult B lymphocytes. This prevalence indicates an importance of VH4-21 in the B-cell repertoire. The gene also encodes certain autoantibodies being mandatory for pathological IgM anti-red cell antibodies directed against the I/i antigen, and also capable of encoding anti-DNA antibodies. Recognition of I/i antigen or DNA appears to be via two distinct sites on VH, with I/i binding mediated by sequences in the framework region, and DNA binding correlating with the presence of positively charged amino acids in complementarity-determining region 3. However, these positively charged residues appear to suppress the ability of the framework region to interact with I/i, rendering a single sequence monospecific for I/i or DNA. The IgM anti-DNA antibodies also recognize bacterial lipid A, whereas the anti-I/i antibodies do not, indicating that CDR3 may be involved in binding the negatively charged lipid A. Structural similarities between the DNA backbone and lipid A provide a possible explanation for this cross-reactivity. This dual recognition of bacterial antigen and autoantigen provides a potential link between infection and autoimmunity.     

Pancreaticoduodenectomy for selected periampullary neuroendocrine tumors: fifty patients

BACKGROUND: Most resectable pancreatic or peripancreatic neuroendocrine tumors are treated by enucleation or distal pancreatectomy. A minority of tumors may require pancreaticoduodenectomy for complete tumor excision because of their large size, location, or lymph node involvement. METHODS: This study reviews the management of 50 patients treated by pancreaticoduodenectomy for periampullary neuroendocrine tumors between 1962 and 1996 at a single institution. RESULTS: There were 30 men and 20 women with a mean age of 52 +/- 2 years. Functional tumors were resected in 17 patients: insulinoma, seven tumors; gastrinoma, eight tumors; vipoma, one tumor; and glucagonoma, one tumor. Tumors were classified as malignant in 29 patients and benign in 21. The median intraoperative blood loss was 800 ml, and the median number of units of blood transfused was zero. The postoperative length of stay was 20 +/- 2 days. Postoperative morbidity included 11 patients (24%) with a pancreatic fistula and four patients (8%) with a biliary fistula. There was one in-hospital death (2%), in 1967. The actuarial survival rates at 2, 5, and 7 years are 81%, 73%, and 65%, respectively. Patients with benign tumors had a significantly improved 5-year survival rate (94%) compared with those with malignant tumors (61%; p = 0.03). CONCLUSIONS: Selected patients with periampullary neuroendocrine tumors can be managed successfully by pancreaticoduodenectomy, with low mortality and acceptable morbidity rates.     

Classifying rehabilitation inpatients by expected functional gain

OBJECTIVES: To create a more suitable payment system for medical rehabilitation, the authors developed a companion classification system to the original functional independence measure-function-related groups (FIM-FRGs), which classify patients having similar lengths of stay in a rehabilitation hospital or inpatient unit. The companion system presented here groups patients according to their gains in functional status during the rehabilitation stay. METHODS: Data from 84,492 patients discharged from 252 rehabilitation facilities in 1992 were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The gain-FRGs system used four predictor variables: (1) diagnosis leading to disability, admission scores on the (2) motor and (3) cognitive subscales of the FIM, and (4) patient age. RESULTS: The gain-FRGs system contained 74 patient groups and explained 21% of the variation in functional gain for patients in a different set of records withheld for validation. CONCLUSIONS: The gain-FRGs system should be considered for prospective payment systems because it gives the provider an incentive to improve patient outcomes, which is missing in a payment system based on FIM-FRGs alone.     

Cardiac rupture with dobutamine stress echocardiography

Dobutamine stress echocardiography is a safe method for the evaluation of coronary artery disease, myocardial function, and viability. The potential for cardiac rupture exists. Although clinical and electrocardiographic criteria may be helpful in identifying those patients at risk for cardiac rupture, the criteria are neither sensitive nor specific enough to exclude patients or make recommendations regarding which patients should undergo dobutamine stress echocardiography in the post-infarction period. Physicians must be aware of the possibility and be prepared to treat cardiac rupture when performing dobutamine stress echocardiography.     

Pain drawings in the assessment of nerve root compression: a comparative study with lumbar spine magnetic resonance imaging

STUDY DESIGN: Prospective comparative study of pain drawings with findings on lumbar spine magnetic resonance imaging. OBJECTIVES: To assess the ability of the pain drawing to predict the presence of nerve root compression. SUMMARY OF BACKGROUND DATA: Most research work has concentrated on the ability of the pain drawing to act as a screening method for psychological distress with less work directed at the influence the anatomic abnormality has on the pain drawing. METHODS: One hundred thirty-four consecutive outpatients attending for lumbar magnetic resonance imaging in the investigation of back and leg pain completed pain drawings and psychological testing immediately before the examination. The pain drawing was analyzed by previously reported criteria, and the magnetic resonance imaging was assessed independently for the presence of nerve compression by three radiologists. Multivariate stepwise discriminant analysis was used to identify patients with nerve compression on the basis of their pain drawing. RESULTS: Nerve compression was predicted by numbness in the anterolateral aspect of the foot. There was considerable overlap in the appearances of the pain drawings between patients with and without nerve compression, and the pain drawing correctly classified only 58% of patients with nerve compression. CONCLUSIONS: The pain drawing is not a good predictor of nerve compression on magnetic resonance imaging in a group of patients investigated for back and leg pain. It should be interpreted with caution and in light of the full clinical picture.