Rational sequence of tests for pancreatic function.
Of 144 patients with suspected pancreatic disease in whom a 75Se-selenomethionine scan was performed, endoscopic retrograde pancreatography (ERP) was successful in 108 (75%). The final diagnosis is known in 100 patients and has been compared with scan and ERP findings. A normal scan reliably indicated a normal pancreas, but the scan was falsely abnormal in 30%. ERP distinguished between carcinoma and chronic pancreatitis in 84% of cases but was falsely normal in five patients with pancreatic disease. In extrahepatic biliary disease both tests tended to give falsely abnormal results. A sequence of tests to provide a rapid and reliable assessment of pancreatic function should be a radio-isotope scan, followed by ERP if the results of the scan are abnormal, and a Lundh test if the scan is abnormal but the findings on ERP are normal. (+info
Activation of alveolar macrophages in lung injury associated with experimental acute pancreatitis is mediated by the liver.
OBJECTIVE: To evaluate (1) whether alveolar macrophages are activated as a consequence of acute pancreatitis (AP), (2) the implication of inflammatory factors released by these macrophages in the process of neutrophil migration into the lungs observed in lung injury induced by AP, and (3) the role of the liver in the activation of alveolar macrophages. SUMMARY BACKGROUND DATA: Acute lung injury is the extrapancreatic complication most frequently associated with death and complications in severe AP. Neutrophil infiltration into the lungs seems to be related to the release of systemic and local mediators. The liver and alveolar macrophages are sources of mediators that have been suggested to participate in the lung damage associated with AP. METHODS: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. The inflammatory process in the lung and the activation of alveolar macrophages were investigated in animals with and without portocaval shunting 3 hours after AP induction. Alveolar macrophages were obtained by bronchoalveolar lavage. The generation of nitric oxide, leukotriene B4, tumor necrosis factor-alpha, and MIP-2 by alveolar macrophages and the chemotactic activity of supernatants of cultured macrophages were evaluated. RESULTS: Pancreatitis was associated with increased infiltration of neutrophils into the lungs 3 hours after induction. This effect was prevented by the portocaval shunt. Alveolar macrophages obtained after induction of pancreatitis generated increased levels of nitric oxide, tumor necrosis factor-alpha, and MIP-2, but not leukotriene B4. In addition, supernatants of these macrophages exhibited a chemotactic activity for neutrophils when instilled into the lungs of unmanipulated animals. All these effects were abolished when portocaval shunting was carried out before induction of pancreatitis. CONCLUSION: Lung damage induced by experimental AP is associated with alveolar macrophage activation. The liver mediates the alveolar macrophage activation in this experimental model. (+info
Enhanced Th1 and dampened Th2 responses synergize to inhibit acute granulomatous and fibrotic responses in murine schistosomiasis mansoni.
In murine schistosomiasis mansoni, CD4(+) Th1 and Th2 cells participate in the ovum-induced granulomatous inflammation. Previous studies showed that the interleukin-12 (IL-12)-induced Th1 response strongly suppressed the Th2-cell-mediated pulmonary granuloma development in naive or primed mice. However, liver granulomas were only moderately suppressed in egg-vaccinated, recombinant IL-12 (rIL-12)-treated infected mice. The present study shows that repeated rIL-12 injections given during early granuloma development at 5 to 7 weeks after infection prolonged the Th1 phase and resulted in gamma interferon-mediated suppression of liver granulomas. The timing is crucial: if given at 6 to 8 weeks, during the Th2-dominated phase of florid granuloma growth, the treatment is ineffective. Daily injections of rIL-12 given between 5 and 7.5 weeks during the period of granuloma growth achieved a somewhat-stronger diminution in granuloma growth with less deposition of collagen but caused 60% mortality and liver pathology. In contrast, combined treatment with rIL-12 and anti-IL-4-anti-IL-10 monoclonal antibody (MAb) injections given during the Th2 phase strongly inhibited liver granuloma growth without mortality. The diminished inflammatory response was accompanied by less deposition of collagen in the liver. Moreover, neutralization of endogenous IL-12 by anti-IL-12 MAbs effectively decreased the early Th1 phase (between 5 and 6 weeks after infection) but not the developing Th2 phase (5 to 7 weeks) of granuloma development. These studies indicate that the granulomatous response in infected mice can be manipulated by utilizing the Th1-Th2-subset antagonism with potential salutary results in the amelioration of fibrous pathology. (+info
Delay in presentation of patients with acute stroke to hospital in Oxford.
We identified prospectively all patients (181 patients, 183 episodes) admitted to hospital in Oxford with acute stroke from 1 January to 30 June 1997. Data were inadequate in 30, leaving 153 episodes in 151 patients (63 men, 90 women). Structured interviews were used to investigate the timing of events preceding admission. Most strokes (91%) occurred at home, and 36% of patients were alone. After a median delay of 15 min, 56% called a GP (median 30 min response), 41% an ambulance (median 48 min to admission), and 3% went directly to A&E. Median time from hospital admission to doctor assessment was 69 min. Factors reducing delay were: initially calling an ambulance rather than a GP (p < 0.0001); onset not at home (p < 0.001); symptoms improving between onset and admission (p < 0.002); and altered consciousness (p < 0.002). The stroke was not recognized by 44% of patients, but no significant delay resulted. Overall, 31% were admitted within 3 h of onset, 46% within 6 h. Initial contact with the GP is a major determinant of delay. If acute therapies for stroke become available, GPs should be the primary targets for an educational initiative. (+info
Assessment of swallowing and referral to speech and language therapists in acute stroke.
The best clinical assessment of swallowing following acute stroke, in order to decide whether to refer a patient to a speech and language therapist (SLT), is uncertain. Independently of the managing clinical team, we prospectively investigated 115 patients (51 male) with acute stroke, mean age 75 years (range 24-94) within 72 h of admission, using a questionnaire, structured examination and timed water swallowing test. Outcome variables included referral to and intervention by a speech and language therapist (SLT), dietary modification, respiratory complications and death. Of those patients in whom an SLT recommended intervention, 97% were detected by an abnormal quantitative water swallowing test; specificity was 69%. An SLT was very unlikely to recommend any intervention if the test was normal. Inability to perform a water test and/or abnormality of the test was associated with significantly increased relative risks of death, chest infection and dietary modification. A timed water swallowing test can be a useful test of swallowing and may be used to screen patients for referral to a speech and language therapist after acute stroke. (+info
Chlamydia pneumoniae and atherosclerosis.
OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae. (+info
Painful incarcerated hernia following a rugby union lineout.
Discussion related to hernias in sport usually involves the diagnosis and treatment of chronic musculotendinous groin disruption. A case of acute trauma in an incarcerated inguinal hernia, occurring in a rugby union player during a lineout, is presented. The injury arose as a result of a change in the laws of the game. (+info
T lymphocyte adhesion mechanisms within inflamed human kidney: studies with a Stamper-Woodruff assay.
Renal inflammatory conditions are characterized by mononuclear cell recruitment to sites of inflammation. We have developed a modified Stamper-Woodruff assay system to analyze mechanisms of functional T cell adhesion to cryostat sections of renal biopsy material from patients with vasculitic glomerulonephritis (GN) and acute allograft rejection. Peripheral blood T cells adhered to intraglomerular, periglomerular, and tubulointerstitial regions of the cortex. Blocking monoclonal antibodies against tissue expressed ICAM-1, VCAM-1, and the CS-1 domain of fibronectin (CS-1Fn) differentially attenuated T cell adhesion. Glomerular adhesion in vasculitic GN and tubulointerstitial adhesion in acute rejection were particularly sensitive to both anti-ICAM-1 and anti-VCAM-1 antibodies, indicating a prominent role for ICAM-1 and VCAM-1 at glomerular sites in vasculitis and at tubulointerstitial sites in rejection. Furthermore, using KL/4 cells (LFA-1 expressing) and Jurkat cells (VLA-4 expressing), we demonstrated specific LFA-1/ICAM-1- and VLA-4/VCAM-1-mediated interactions within glomerular and tubulointerstitial compartments. Jurkat cells also adhered to VCAM-1-free sites, and binding was inhibitable by anti-CS-1Fn antibody, thereby demonstrating a role for VLA-4/fibronectin interactions especially at intraglomerular sites in acute rejection where VCAM-1 is notably absent. We therefore propose a prominent functional role for ICAM-1, VCAM-1, and CS-1 domain fibronectin in T cell recruitment to the inflamed kidney. (+info