Obstruction of proximal tubules initiates cytoresistance against hypoxic damage

Following acute tubular necrosis (ATN), cytoresistance to further renal injury results. However, the initiating events and the subcellular determinants of this phenomenon have not been defined. Since tubular obstruction is a consequence of ATN, this study evaluated whether it alters tubular susceptibility to hypoxic damage. Extrarenal obstruction (ureteral ligation in rats) was used for this purpose to dissociate obstructive effects from those of ATN. Twenty-four hours following ureteral ligation or sham surgery, cortical proximal tubular segments (PTS) were isolated and subjected to hypoxic (15 or 30 min)/reoxygenation injury. Since oxidant stress, cell Ca2+ overload, and PLA2 attack are purported mediators of hypoxic/reoxygenation injury, degrees of FeS04, Ca2+ ionophore, and phospholipase A2-induced PTS damage also were assessed. The cell injury (% LDH release) which resulted from each of the above was consistently less in PTS obtained from obstructed kidneys. This cytoresistance: (a) did not require prior uremia to develop (seen with unilateral obstruction); (b) it did not appear to correlate with a tubular proliferative response (assessed by proliferating cell nuclear antigen expression); (c) it was uninfluenced by early tubular repair (unchanged by 24 hrs of obstruction release); and (d) it occurred without increased heat shock protein (HSP-70) or antioxidant enzyme (superoxide dismutase, catalase) expression. Total adenylate pools were higher in obstructed versus control PTS during injury; however, this appeared to be a correlate of the protection, rather than a mediator of it. In contrast, obstructed tubules manifested a primary increase in plasma membrane resistance to PLA2 attack (approximately 3-fold less lysophosphatidylcholine and free fatty acid generation in obstructed vs. control PTS during incubation with exogenous PLA2). In sum, these results indicate that: (1) tubular obstruction protects PTS from injury, suggesting that its development during ATN may initiate cytoresistance; and (2) this cytoresistance appears to be mediated, at least in part, by a direct increase in plasma membrane resistance to PLA2 and potentially other forms (such as, oxidant stress, cytosolic Ca2+ loading) of attack.     

MR cholangiopancreatography: technique, indications and clinical results

INTRODUCTION: MR cholangiopancreatography (MRCP) is a new noninvasive imaging technique for the study of biliopancreatic disorders, providing projectional images of the biliary tree and pancreatic duct without any contrast agent. MATERIAL AND METHODS: We used different sequences, with both breath-hold and nonbreath-hold techniques, to acquire MRCP images, first based on GE and then on FSE sequences. FSE images provide higher SNR and are less susceptible to artifacts (metal objects, motion and blood flow artifacts). At the Department of Radiology of the University of Rome La Sapienza, we acquired MRCP images with non breath-hold, 3D fat-suppressed TSE sequences (TR = 3000-2000, TE 700, turbo factor 128) optimized on a .5T magnet with 15 mT/m gradients. No patient preparation or sedation was required, although antiperistaltic drugs and oral administration of tap water were preferred. Four hundred and thirty patients were examined, all of them with an indication to conventional cholangiography. RESULTS: MRCP depicted the whole common bile duct and the first-order intrahepatic branches in all the normal cases. Its accuracy in identifying biliary obstruction level and site was 100%, versus 94.6% in characterizing its cause. MRCP had 96.3% diagnostic accuracy in choledocholithiasis, with some false positives and false negatives caused by: 1) small stones missed on MIP reconstructions; 2) signal loss due to complete CBD obstruction by stones; 3) pneumobilia; 4) differential diagnosis between small stones and air bubbles. The main role of MRCP in benign strictures is to provide a detailed map of the biliary tract for better treatment planning. In particular, MRCP is extremely useful in hepaticojejunostomy patients, where ERC is not indicated because of postoperative anatomical changes. Both conventional MRI and MRCP are important in malignant strictures to identify the lesion and to characterize and stage it. Finally, MR pancreatography is very useful to follow up chronic pancreatitis patients because it shows Wirsung duct strictures and dilatations, intraductal filling defects and, in some cases, the communication between the pseudocyst and the pancreatic duct. CONCLUSIONS: MRCP combined with conventional MRI can completely replace CT and ERCP in bilio-pancreatic disorders.     

Effect of experimentally induced urethral obstruction and surgical decompression in utero on renal development and function in rabbits

To investigate the effect of urethral obstruction during late fetal life on renal development and function, we developed a rabbit fetal model of obstructive nephropathy to examine the pathological and biochemical consequences of urethral obstruction and beneficial effects of early surgical decompression. Animals were divided into four groups, i.e., obstructed, early decompressed, late decompressed, and control. Fetal renal development was evaluated by histological examination and counting the number of glomeruli in the four groups. The number of renal glomeruli correlated with gestational age in the normal fetus (r = 0.90, P < 0.0001). Urethral ligation on gestational day 25 (full-term, 31 days) resulted in thinning of the renal cortex and significantly decreased the number of renal glomeruli. The concentration of urinary microalbumin was higher when urethral obstruction was maintained for 3 days than 1 day after urethral obstruction, although urinary beta2- microglobulin, Na, Cl, and osmotic pressure did not change during this period. Decompression of urethral obstruction 1 day after induction of urethral obstruction resulted in improvement in the severity glomerular hypoplasia compared with late decompression (P < 0.01). Our results suggest that the rabbit fetal model simulates fetal urethral obstruction in humans, and indicates that early surgical decompression may be effective in restoration of normal renal function.     

Familial dementia lacking specific pathological features presenting with clinical features of corticobasal degeneration

A family is described in which one member presented with symptoms and signs suggestive of corticobasal degeneration and a sibling presented with features of a frontal lobe dementia. Their mother developed a presenile dementia and movement disorder. At postmortem examination the member with clinical corticobasal degeneration had non-specific pathological features. Therefore, the clinical features of corticobasal degeneration can occur with non-specific pathological changes. Within a pedigree, different members can present with different clinical syndromes, which may reflect variation in the distribution and severity of the pathological process.     

Endoscopic biliary manometry in cholecystectomized patients with and without choledocholithiasis

BACKGROUND/AIMS: Direct study of the function of the sphincter of Oddi became possible recently with the advent of endoscopic manometry. A dysfunction of the bilio-pancreatic sphincter apparatus has been implicated in some bilio-pancreatic disorders. The purpose of this study was to examine the relation between dysfunction of the sphincter of Oddi and the formation of common bile duct stones. METHODOLOGY: Endoscopic biliary manometry was performed on 45 cholecystectomized patients. Endoscopic retrograde cholangiography showed choledocholithiasis in 26 patients while 19 patients were free of common bile duct stones. Nine healthy subjects served as controls. RESULTS: Manometric investigation showed a significant increase in the percentage of retrograde phasic contractions of the sphincter of Oddi (SO) in patients with choledocholithiasis compared to the control group (p < 0.05). Also, a significantly higher frequency of SO phasic contractions was found in the group of patients with choledocholithiasis when compared to the cholecystectomized group without common bile duct stones (p < 0.05), but there was no difference when compared with the control group. Markedly increased SO basal pressure was found in 5 patients with choledocholithiasis as well as in one cholecystectomized patient without choledocholithiasis (greater than x + 3SD). However, the SO basal pressure, phasic SO pressure, amplitude and duration of the phasic contractions as well as the choledochal pressure did not differ significantly between the groups. CONCLUSIONS: This study demonstrates manometric abnormalities in the SO of patients with choledocholithiasis which suggests that SO dysfunction and pathophysiological mechanisms are related to the formation of common bile duct stones.     

Airway remodeling: potential contributions of subepithelial fibrosis and airway smooth muscle hypertrophy/hyperplasia to airway narrowing in asthma

Recently, much attention has been focused on the airway structural changes accompanying chronic, severe asthma, and the potential ramifications of these changes for airway function and medical management. Airway remodeling may exaggerate airway narrowing by: (i) thickening of the airway wall internal to the smooth muscle, thereby increasing the luminal obstruction generated by a given degree of smooth muscle shortening; (ii) increasing the amount of smooth muscle, thereby increasing shortening; and/or (iii) reducing the load on the smooth muscle, either by increasing the compliance of the airway wall or by reducing airway-parenchymal interdependence. The possibility also exists that airway remodeling represents a protective mechanism against excessive airway narrowing. The major airway structural changes occurring in asthma are subepithelial protein deposition and increased airway smooth muscle mass (hypertrophy, hyperplasia, or both). Several investigators have found correlations between the magnitudes of subepithelial thickening and smooth muscle hypertrophy/hyperplasia and the severity of airways disease, though interpretation has been made difficult by study differences in patient population, treatment, indices of disease severity, and morphometric technique. Taken together, these data suggest that increases in airway remodeling may contribute significantly to the airflow obstruction observed in patients with asthma. However, data proving a causal relationship between airway remodeling and asthma severity remain elusive.     

Stages of Change in Treatment-Seeking Pathological Gamblers.

The transtheoretical model has been applied to many addictive disorders. In this study, psychometrics properties of the University of Rhode Island Change Assessment (URICA) scale were evaluated in 234 pathological gamblers initiating treatment. Four components were identified--reflective of precontemplation, contemplation, action, and maintenance stages--with internal consistency from .74 to .88. Cluster analyses identified 4 patterns of responding, ranging from ambivalent to active change. The 4 clusters differed with respect to baseline gambling variables and treatment engagement and outcomes assessed 2 months later. A continuous measure of readiness to change was also correlated with gambling severity and predictive of reductions in gambling. This study provides initial support for reliability and validity of the URICA in treatment-seeking gamblers, and it suggests that stage of change may have an impact on outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase

Idiopathic Parkinson's disease (IPD) is characterised by the loss of pigmented neurones in the substantia nigra, leading to reduced tyrosine hydroxylase activity and depletion of dopamine. Treatments attempt to correct this deficit by the use of levodopa and inhibitors of dopamine metabolising enzymes such as catechol-O-methytransferase (COMT). A common amino-acid polymorphism in COMT, valine-108-methionine, results in a low activity form of the enzyme which we hypothesised may influence susceptibility to IPD. We examined this polymorphism in 139 Caucasian subjects with IPD and 173 control subjects, using a PCR-RFLP and a novel Amplification Refractory Mutation System (ARMS) assay. Allele and genotype frequencies were similar in the affected and control subjects, indicating that variation of COMT activity is not an aetiological factor in IPD. We have also characterised a new polymorphism, 256C/G, which is not associated with IPD. However it remains possible that allelic variation in COMT influences severity, type of pathology or treatment response to levodopa or COMT inhibitors.     

Thalassaemia and malaria, revisited

Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that alpha thalassaemia provides protection against severe malaria. Quite unexpectedly at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life.     

Bilateral encephalomalacia in a pig related to latent Aujeszky''s disease virus infection

Transcranial Doppler studies on the effects of sumatriptan on cerebral hemodynamics have shown conflicting results. We evaluated blood flow velocity changes in 21 patients suffering from migraine with (n = 4) or without aura (n = 17) during a spontaneous attack, before and after treatment with sumatriptan. Flow velocity in the internal and external carotid, middle cerebral, and basilar arteries was measured by means of transcranial Doppler. During the attack, measurements were taken before subcutaneous sumatriptan injection, then after 30 minutes, 2 hours, and 24 hours. An additional measurement was taken 1 week later, in a headache-free state. We found a significant reduction of flow velocity during the attack in the middle cerebral artery on both sides (P < 0.05). After sumatriptan administration, flow velocity increased in the internal carotid artery on both sides (P < 0.05) and in the middle cerebral artery on the headache side (P = 0.0001), but not in the external carotid and basilar arteries (P > 0.05). Flow velocity changes may reflect the vasodilation present at the onset of the migraine attack followed by vasoconstriction in the internal carotid and middle cerebral arteries after sumatriptan treatment. Since vasoconstriction occurs in responders and nonresponders to treatment, it is unlikely to be the primary mechanism by which sumatriptan relieves headache.     

Tidal expired airflow patterns in adults with airway obstruction

Earlier studies have shown that time and flow indices derived from tidal expiratory flow patterns can be used to distinguish the severity of airway obstruction. This study was designed to address two aspects of tidal expiratory flow patterns: 1) how do expiratory flow patterns differ between subjects with normal and obstructed airways; and 2) can a sensitive index of airway obstruction be derived from these pattern differences? Tidal expiratory flow patterns from 66 adult subjects with varying degrees of airway obstructive disease with a forced expiratory volume in one second (FEV1) of 20-121% predicted were examined. In each subject, the expired flow pattern from each consecutive breath was scaled and then averaged together to create a single expired pattern. A detailed examination of the scaled flow patterns in 12 subjects (six with normal airways and six with airway obstruction) showed that the shape of the post-peak expiratory flow portion was different in the subjects with airway obstruction. A slope index, S, was derived from the scaled patterns and found to be sensitive to the severity of airway obstruction, correlating with FEV1 (% pred) with r2=0.74 (p<0.05, n=57). The S index also correlated (r2=0.36, p<0.05, n=47) with the functional residual capacity (FRC) (% pred) which was >100% in subjects with severe airway obstruction and lung overinflation. In subjects with normal airways, three further airflow patterns could be distinguished, which were different from the patterns seen in subjects with the severest airway obstruction. Scaled flow patterns from tidal expiration collected from uncoached subjects, can be used to derive an index of airway obstruction.     

Battery-cages as the cause of environmental and behavioural dependent diseases (author's transl)

Bone fragility and increased fat content in the liver of egg-laying hens are more often encountered in birds from traditional battery-cage systems than in those confined in other systems. By reviewing the relevant literature possible explanations of these phenomena are proposed. Clinical and pathological manifestations of the syndromes are described and a number of possible aetiological factors are evaluated. Bone fragility can be seen either as a general weakness of bone tissue or as a clinically manifest disease, Cage layer fatigue. It is concluded, that general restriction of the animal's possibilities to locomote and perform comfort movements are the most important aetiological factors. Fatty liver disease may be seen either as a pathological elevation of the liverfat content or it may be seen as a disease called Fatty liver haemorrhagic syndrome. Several factors may cause elevation of the liver fat content. The influence of restricted movement on the animals energy balance, however, like other behavioural disturbances seems to be the most important aetiological factors. It is concluded, that bone fragility and fatty liver in egg-laying hens are diseases caused by an inadequate environment and the restriction of essential behavioural patterns.     

Advanced life support guidelines. European Resuscitation Council

In order to investigate the relationship between the size of the adenoid and upper respiratory symptoms in children, fibreoptic examination of the nasal cavity and nasopharynx was performed in 817 children. The size of the adenoid was classified into three categories according to the distance between the vomer and the adenoid tissue. There was a significant relation between the size of the adenoid and the complaints of nasal obstruction (P < 0.001) and of snoring (P < 0.001), but not with the presence of purulent sinusitis. In the whole population, the size of the adenoid correlated well with the results of tympanometry (P < 0.001), but this does not hold in all age groups. This study has confirmed adenoid hypertrophy as a common aetiological factor in children with the complaints of nasal obstruction and snoring. The enlargement of the adenoid only partially explains the occurrence of otitis media with effusion. The introduction of the flexible fibrescope in the examination of the nasal cavity and nasopharynx in children is of great clinical value, especially in the selection of children for adenoidectomy. It is a minor invasive examination well tolerated by most children, giving more information than a lateral skull radiograph and avoiding unnecessary radiation.     

Physiologic diagnosis and function in asthma

Asthma is a condition in which there is airway hyperresponsiveness, with the propensity for widespread, reversible airways narrowing on exposure to diverse inciting factors (triggers). Inhalation of nonspecific agents such as methacholine or histamine leads to bronchoconstriction in most cases, and in some, the bronchoconstriction follows exposure to specific agents such as antigen or occupational irritants. Chest tightness and cough, which are the most common symptoms of asthma, are probably the result of inflammation mucus plugs, edema, or smooth muscle constriction in the small peripheral airways. Because major obstruction of the peripheral airways can occur without recognizable increases of airway resistance or FEV1, the physiologic alterations in acute exacerbations are generally subtle in the early stages. Poorly ventilated alveoli subtending obstructed bronchioles continue to be perfused, and as a consequence, the P(A-a)O2 increases and the PaO2 decreases. At this stage, ventilation is generally increased, with excessive elimination of carbon dioxide and respiratory alkalemia. In the more severe exacerbation, lung volume is increased and the static volume-pressure curve is shifted up (lung volume is greater) and to the left (pressure is lower) while the shape of the curve is unaltered. The airway obstruction is reversible and there is generally improvement in air flow rates following administration of beta-agonists and anti-inflammatory agents. The changes in mechanical properties are also reversible, and therapeutic intervention usually results in a shift of the PV curve downward toward the normal position, for example, a decrease in TLC and an increase in the elastic recoil pressure at any particular lung volume. Failure to take these changes into account may underestimate the impact of therapy. The PaO2 decreases (and the P(A-a)O2 increases) as the work of breathing increases, and when it becomes excessive (and/or the FEV1 falls below 20% to 25%), the PaCO2 begins to increase. Therefore, in any patient with asthma, a decreasing PaO2 and an increasing PaCO2, even into the normal range, indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.     

Pathology of mitral valve in regularly slaughtered pigs: an abattoir survey on the occurrence of myxoid degeneration (endocardiosis), fibrosis and valvulitis

The aim of this study was to report the prevalence of degenerative and early inflammatory lesions and to discuss some histological aspects of normal and pathological mitral valve leaflets in healthy, normally slaughtered pigs. Mitral valves were collected from 112, 6 month-old, pigs reared under different conditions. Histological examination revealed the presence of myxoid degeneration in 29.5% of the valves with no significantly different prevalence according to rearing conditions; fibrosis was present in 12.5%; inflammation (non-vegetative valvulitis) occurred in 20 (17.9%) macroscopically normal valves. No vegetative endocarditis could be observed. A significantly higher degree of inflammation was observed in valves affected by myxoid degeneration (P < 0.05) and Anitschkow cells were prevalent in all the pathological valves (P < 0.01). Capillaries were observed in a wide majority of the valves (86.5%), but small arterioles were related to fibrotic thickening of the leaflets (P < 0.01). The following conclusions are discussed: (1) environmental factors seem not to influence the prevalence of endocardiosis; (2) inflammatory foci in myxoid valves are a reaction to both abnormal friction and products of degraded collagen and extracellular matrix; (3) the authors consider the presence of capillaries in pig valves a normal finding whereas proliferation of the vessels occurs under pathological conditions; (4) non vegetative valvulitis can be related to the presence of vessels in the valve and may have a role in both infectious endocarditis and fibrosis; (5) Anitschkow cells are normally observed in pig valves and are not specifically related to pathological lesions.     

Critical review of psychometric tests

Macroscopic haematuria is common in IgA nephropathy, but its significance and influence on prognosis remains uncertain. We compared the clinical and pathological features of 11 adult patients with primary IgA nephropathy who had had a renal biopsy during or shortly after a bleeding episode. Six patients developed transient acute renal failure (ARF) (group 1) and five did not (group 2). Patients of group 1 had a higher percentage of tubular red-blood-cell (RBC) casts (P < 0.05) and of glomerular crescents (P < 0.001). However, crescents were focal and involved less than 50% of glomeruli. Acute tubular necrosis was only present in patients of group 1, and ARF was attributed to the acute tubular changes rather than to the glomerular lesions. Despite a prolonged duration of ARF (mean: 38 days), further outcome did not differ in patients of both groups. We suggest that acute tubular damage and/or tubular obstruction by RBC casts should be considered in any patient who develops ARF soon after a haematuric episode.     

Construction of a bridge with implantation of Linkow plates

The aetiological diagnosis of a unilateral nonfunctioning kidney is achieved by angiographic or retrograde techniques. Pyelography indicates only that organ is non-functioning. 71 patients were explored by nephro-urotomography carried out using high doses of contrast medium (2 cm3/kg) with rapid injection (10cm3/sec.) and repeated tomographic sections taken during the first minute after injection. These tomographic sections, three in number, made it possible to study the three phases of the nephrogram: cortical nephrography, cortico-medullary nephrography and tubular nephrography. The aim of this study was to assess the contribution of this technique in the aetiological diagnosis of a unilateral non-functioning kidney. In the majority of cases it is possible to suspect the vascular or neoplasic origin of the non-functioning kidney. Obstructive non-functioning kidneys have two distinct nephrographic appearances. Pelvic and retroperitoneal obstructions are visualised chiefly during the phase of cortical nephrography, which shows marked parenchymatous atrophy with the presence of rounded intrarenal lacunae. By contrast, obstruction secondary to pyelo-ureteral junction syndrome results in total destruction of the parenchyma. The phenomenon of total corporeal opacification plays a major role in the visualisation of the fibrous speta which form the limits of the pseudocystic pockets. In these patients, the contribution of study of early nephrograms is less evident. Bacillary non-functioning kidneys have an analogous appearance characterised by the particular frequency of abnormal opacities, calcified ormastic. Thus the aetiological diagnosis of a unilateral nonfunctioning kidney may be obtained in the majority of cases. This permits more judicious selection of those cases requiring angiography or retrograde exploration necessary to pre-operative assessment.     

Pathological changes according to the severity of asthma

BACKGROUND: There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. OBJECTIVE: This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histological abnormalities in asthmatics according to the severity of asthma. METHODS: Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inflammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultrastructural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina. CONCLUSION: These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.     

Pseudotumor aspect of ovarian vein thrombosis

Peritoneal lavage is one of the interventional approaches that have gained some attention in the early, toxaemic phase of acute pancreatitis. Additionally some kind of drainage is necessary for suppurative collections that characterize the late phase of the disease. In both the above situations tube plugging is a common problem and it is usually associated with a relapse of the patient's septic state and newly formed collection(s) on abdominal CT. Two cases are presented, in early and in late phases respectively, in which drainage tube adoscopy (DTE) re-established tube patency and ensured drainage. DTE may represent an alternative to surgery or to CT-guided paracentesis and evacuation of newly formed intra-abdominal collections secondary to tube obstruction.