Degree Of Organ Damage Research Articles

Pancreatic injury, genetic variation of PNPLA3, and risk of pancreatic cancer.

141 Background: Similar to primary liver cancer, obesity, diabetes mellitus and hepatitis B virus infection have been associated with increased risk of pancreatic cancer (PC) development. A genome-wide association study has reported that a polymorphic variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene was associated with a higher susceptibility to fatty liver and liver cancer. The relationship between this variation and PC has not been previously examined. We investigated the correlation in the degree of organ damage between the liver and the pancreas in patients with PC. In addition, we examined the effect of PNPLA3genetic variation (rs738409: C>G) on PC development. Methods: Using resources of our case-control study in MD Anderson Cancer Center, we analyzed 544 pathologically confirmed PC patients and 498 healthy controls. Cases and controls were frequency matched by age, gender, and race. Multivariate logistic regression analysis was performed to adjust for the confounding factors. Medical records of PC patients were reviewed for pancreatic and liver fatty changes. Results: We found that 18.8% of PC patients had evidence of pancreatic steatosis, fibrosis, or pancreatitis. Fatty liver was observed in 14.5% of PC patients which was frequently detected in patients with pancreatitis (p=0.002). A significant correlation between pancreatitis and cirrhosis was observed in PC patients with a prior history of obesity but not in patients without a history of obesity (p=0.001). On the other hand, we observed no significant association between PNPLA3 genotype and risk of PC. The adjusted odds ratio (OR) was 1.4 (95% confidence interval [CI], 0.7-2.7) for the homozygous variant GG genotype compared with the CC/CG genotypes. Conclusions: We concluded that despite the similarities between the liver and the pancreas, genetic susceptibility to fatty infiltration and its effect on cancer development may differ between the two organs. Evaluation and assessment of nonalcoholic fatty pancreatic disease (NAFPD) in PC patients and genetic susceptibility of NAFPD may be warranted in future research.

Pancreas and Liver Injury Are Associated in Individuals With Increased Alcohol Consumption

Although chronic pancreatitis and liver cirrhosis are common sequelae of excess alcohol consumption, the 2 conditions are rarely associated. We studied the prevalence of simultaneous liver cirrhosis and chronic pancreatitis in alcoholics. Postmortem autopsy data from 620 individuals with a history of excess alcohol consumption and 100 nonalcoholics (controls) were analyzed. The individuals were classified into groups based on macroscopic observations of pancreas (no injury, acute pancreatitis, fibrosis, and chronic pancreatitis) and liver (no injury, moderate steatosis, severe steatosis, and cirrhosis). The same classification system was used for histological data, which was used to confirm and correlate macroscopic results. Out of the 183 patients with liver cirrhosis, 33 (18%) had chronic pancreatitis and 93 (51%) had pancreatic fibrosis. Out of the 230 patients with severe steatosis, 37 (16%) had chronic pancreatitis and 97 (42%) were found to have a pancreatic fibrosis. Thirty-three (39%) with chronic pancreatitis also showed liver cirrhosis and 37 (44%) showed severe steatosis. Thirty-eight percent of the patients with a pancreatic fibrosis were found also to have liver cirrhosis and in another 40% severe steatosis. Thirty-five patients showed neither hepatic or pancreatic injury. We found no chronic pancreatitis or liver cirrhosis in the control group (n = 100). Contrary to common belief there is a close association between pancreatic and hepatic injury in patients with increased alcohol consumption, and the degree of organ damage between the 2 organs correlate.

Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients

IntroductionSystemic lupus erythematosus (SLE) is a multi-system autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; thus, there is increasing interest in identifying biomarkers for SLE. In this study we correlated the combined expression level of multiple interferon-inducible chemokines with disease activity, degree of organ damage and clinical features in SLE, and we investigated their roles as biomarkers.MethodsPeripheral blood cells obtained from 67 patients with SLE patients, 20 patients with rheumatoid arthritis (RA) and 23 healthy donors were subjected to real-time PCR in order to measure the transcriptional levels of seven interferon-inducible chemokines (RANTES, MCP-1, CCL19, MIG, IP-10, CXCL11, and IL-8). The data were used to calculate a chemokine score for each participant, after which comparisons were performed between various groups of SLE patients and control individuals.ResultsChemokine scores were significantly elevated in SLE patients versus RA patients and healthy donors (P = 0.012 and P = 0.002, respectively). Chemokine scores were correlated positively with SLE Disease Activity Index 2000 scores (P = 0.005) and negatively with C3 levels (P < 0.001). Compared with patients without lupus nephritis and those with inactive lupus nephritis, chemokine scores were elevated in patients with active lupus nephritis, especially when their daily prednisone dosage was under 30 mg (P = 0.002 and P = 0.014, respectively). Elevated chemokine scores were also associated with the presence of cumulative organ damage (Systemic Lupus International Collaborating Clinics/American Society of Rheumatology Damage Index ≥ 1; P = 0.010) and the occurrence of anti-Sm or anti-RNP autoantibodies (both P = 0.021).ConclusionsThe combined transcription level of interferon-inducible chemokines in peripheral blood leucocytes is closely associated with disease activity, degree of organ damage, and specific autoantibody patterns in SLE. The chemokine score may serve as a new biomarker for active and severe disease in SLE.

Impairment of microcirculation in the early reperfusion period predicts the degree of graft pancreatitis in clinical pancreas transplantation.

Graft pancreatitis is thought to be induced by ischemia/reperfusion. Animal experiments have suggested that an impaired microcirculation is crucial in this process. We have therefore studied the relevance of microcirculation in clinical pancreas transplantation. In 17 patients undergoing pancreas transplantation, tissue pO2 was monitored continuously by an electrode implanted into the pancreatic tail. A catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were taken from this catheter and blood flow was measured by the venous outflow method. The degree of graft pancreatitis was assessed by peak-C-reactive protein (CRP) defined as highest CRP within 3 days after transplantation. Tissue pO2 increased within 5 min after reperfusion. Thereafter, in most patients a transient decrease was noted, indicating impairment of nutritive perfusion. During this period there was an increasing negative correlation between peak-CRP and tissue pO2 which was highly significant at 60 min after reperfusion (r=-0.70, P<0.002). Also donor age correlated significantly with peak-CRP (r=0.64, P<0.005) and to a somewhat lesser extend with tissue pO2 60 min after reperfusion (r= -0.55, P<0.03). These data show that the degree of organ damage in clinical pancreas transplantation is directly related to an impairment of microcirculation in the early reperfusion period. These data also support the idea that grafts from older donors have a higher probability to develop graft pancreatitis and that this might be due to an increased incidence of microcirculatory disturbances in these organs.

Impairment of pancreatic microcirculation in the early reperfusion period correlates with degree of organ damage in clinical pancreas transplantation

Impairment of pancreatic microcirculation in the early reperfusion period correlates with degree of organ damage in clinical pancreas transplantation

Pulsatile compression of the rostral ventrolateral medulla in hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

Normal sympathetic vasomotor and cardiac parasympathetic activities in patients with primary aldosteronism: assessment by spectral analysis

The role of the autonomic nervous system in hypertension due to mineralocorticoid excess remains unclear. To address this issue, we performed power spectral analysis of blood pressure (BP) and RR interval oscillations in 20 patients with primary aldosteronism (PA), 54 patients with essential hypertension (EH) and 45 normotensive (NT) subjects. Blood pressure and the degree of organ damage were similar between PA and EH groups. Age did not differ between the three groups. The Mayer wave power spectrum (MWP) of BP (approx. 0.1 Hz), an index of sympathetic vasomotor tone, was smaller in patients with PA than in patients with EH either while subjects were supine (systolic/diastolic; 3.9 ± 3.2 (SD)/1.5 ± 1.3 vs. 5.5 ± 4.2/2.1 ± 1.6 mmHg 2, P < 0.05 for both) or standing (7.6 ± 6.6/3.0 ± 3.0 vs. 17.7 ± 23.7/7.2 ± 8.3 mmHg 2, P < 0.05 for both). Supine respiratory-related power spectrum (RRP) of the RR interval (approx. 0.25 Hz), an index of cardiac parasympathetic tone, was greater in patients with PA than in patients with EH (545 ± 574 vs. 302 ± 464 ms 2, P < 0.01). The MWP of BP and the RRP of the RR interval were similar between patients with PA and NT subjects. Adrenalectomy reduced the 24-h mean BP (−18 mmHg for systolic BP, P < 0.001; −12 mmHg for diastolic BP, P < 0.01) and increased the 24-h mean heart rate (+8 bpm, P < 0.001). Furthermore, the diastolic MWP increased mildly (+32%, P < 0.05) and the RRP of the RR interval decreased dramatically (−75%, P < 0.01) following adrenalectomy. These results suggest that both vascular sympathetic and cardiac parasympathetic regulatory systems have minor roles in the maintenance of hypertension in patients with PA. The autonomic nervous system contributes more to the maintenance of BP following than prior to adrenalectomy. This information may be useful for the management of hypertension still persists after removal of adrenal adenoma.

Haematology of the haemolytic uraemic syndrome

The Haemolytic Uraemic Syndrome (HUS), characterised by a microangiopathic haemolytic anaemia, thrombocytopaenic purpura and renal failure, is the commonest cause of acute renal failure in children. Most cases of HUS are associated with enteropathogenic Escherichia coli which elaborate an exotoxin called verotoxin. Verotoxin has been shown to produce red cell abnormalities and induce a platelet aggregating activity. It also exerts a cytopathic effect on cultured endothelial cells. These findings are discussed in relation to the pathogenesis of HUS. Recent studies demonstrating homology between the verotoxin glycolipid receptor and the red cell P group antigens have led to the hypothesis that variability in the expression of these red cell antigens may account for the marked individual variations in the degree of organ damage in children with HUS. This hypothesis could provide a criterion for rational immunisation of at risk children.

Thoraco-abdominal injuries

T HE DIAGNOSIS of thoraco-abdomina1 injuries requires menta1 projection of considerable knowIedge and more mental gymnastics and more finesse in management than aImost any other type of injury. The diagnosis of these injuries requires, as a minimum, a knowIedge of regiona anatomy and proper and compIete physica examinations. Certain anciIIary information is heIpfu1, but not essential to successfu1 diagnosis. This information covers such points as position of patient and assaiIant at the time of injury, type of instrument and manner of manipuIation or method of impact, and so forth. A detaiIed knowIedge of regiona anatomy is without question absolutely essentia1. One must practice drawing straight Iines through the body, using any point as the entrance of a buIIet, projecting the Iine in many different angIes and trying to visualize the various organs involved. To make this exercise a bit Iess arduous, the reader shouId know that in 90 per cent of buIIet wounds the course of the missiIe is straight from entrance to exit or to point of Iodging. The stories of buIIets or missiIes ricocheting around in circIes are oId wives’ taIes and can be readiIy expIained by knowing the position of the patient at the moment of wounding. For exampIe, a case was that of a soIdier hit by a single buIIet traveling in a straight line. (Fig. I.) This missiIe involved the Ieft Iower Iobe of the lung, diaphragm, stomach, Iarge bowel, spIeen and Ieft kidney. (Fig. 2.) This soIdier was Iying down with Ieft side up, facing up a hi& and was shot as the enemy came over the hilltop. A gIance at Figure z shows how straight was the buIIet’s course, but this is regional anatomy which was never taught in the past in medica schoo1 cross sectiona anatomy. Practice in projection of straight Iines traversing the body in many different directions is exceIIent preparation for proper diagnosis of organ invoIvement. KnowIedge of the mobiIity of organs and extremes of their dispIacement in the norma human being is vital. As an exampIe, a buIIet wound with entrance just media1 to the midcIavicuIar Iine anteriorly, entering the Ieft portion of chest through the third intercosta1 space (nicking the superior border of the fourth rib) and exiting posteroIateraIIy on a Iine paraIIe1 with the ground, resuIted in invoIving the stomach and spIeen. The answer simpIy is that the man was squatting and was in deep expiration at the time of wounding. The extremes of diaphragmatic excursion in deep inspiration and expiration are depicted in Figure 3. OccasionaIIy, one sees instances of wounding in which, at first gIance, ricocheting of the missiIe is seriousIy considered; for exampIe, a wound of entrance high in the chest anteriorIy with a missiIe found posteriorIy in the chest at the IeveI of the eIeventh rib posteriorIy. CIose examination of the roentgenogram reveaIed that the rib posteriorly, at the same IeveI of the anterior wound of entrance, had been fractured. Thus, the expIanation is simply that the missile traveling in a straight Iine hit a rib posteriorIy and (either having a Iow veIocity or near a high veIocity end point) was stopped by the posterior portion of the rib, dropped free in the pIeura1 cavity and came to rest deep in the posterior costophrenic angIe. KnowIedge of buIIet veIocity and the distance of air trave1 gives vaIuabIe information as to organ damage [I]. There is a direct proportion between the degree of organ damage and muzzIe veIocity. A missiIe of high velocity does far more damage by its “shock wave” than by the simpIe hoIe it makes. This is, of course, more evident in solid organs and is even more important in hemorrhage from late or delayed necrosis. In the use of knives, information as to the