Abstract: Bedside focused echocardiography diagnosis of massive pulmonary embolism during cardiac arrest is mainly based on the detection of a dilated right ventricle, while the lack of compressibility of a deep vein of the lower limbs confirms diagnosis in doubtful cases. We describe a case of unusual sonographic signs in a young woman with cardiac arrest due to massive pulmonary embolism showing spontaneous blood echogenicity in the inferior vena cava (ââsludge signââ) and nonmodulated (ââflatââ) Doppler waveform in the left lower limb veins, suggesting isolated iliac vein thrombosis.
Abstract: Bedside lung ultrasound (LUS) is useful in detecting radio-occult pleural-pulmonary lesions. The aim of our study is to compare the value of LUS with other conventional routine diagnostic tools in the emergency department (ED) evaluation of patients with pleuritic pain and silent chest radiography (CXR).
Abstract: The purpose of this study is to provide evidence-based and expert consensus recommendations for lung ultrasound with focus on emergency and critical care settings.
Abstract: Chronic heart failure is a complex clinical syndrome often characterised by recurrent episodes of acute decompensation. This is acknowledged as a major public health problem, leading to a steadily increasing number of hospitalisations in developed countries. In decompensated heart failure, the redistribution of fluids into the pulmonary vascular bed leads to respiratory failure, a common cause of presentation to the emergency department. The ability to diagnose, quantify and monitor pulmonary congestion is particularly important in managing the disease. Lung ultrasound (US) is a relatively new method that has gained a growing acceptance as a bedside diagnostic tool to assess pulmonary interstitial fluid and alveolar oedema. The latest developments in lung US are not because of technological advance but are based on new applications and discovering the meanings of specific sonographic artefacts designated as B-lines. Real-time sonography of the lung targeted to detection of B-lines allows bedside diagnosis of respiratory failure due to impairment of cardiac function, as well as quantification and monitoring of pulmonary interstitial fluid. Lung US saves time and cost, provides immediate information to the clinician and relies on very easy-toacquire and highly reproducible data.
Abstract: Lung ultrasound is extremely useful in the bedside diagnosis of pneumothorax. The lung point, which is the sonographic demonstration of the point on the chest wall where the pleural layers adhere again, represents the limit of the pneumothorax extension and allows estimation of its volume. This sonographic sign is not only highly accurate in ruling-in pneumothorax but also helps the clinician in deciding whether to place a chest tube. We report a case of a young patient with spontaneous pneumothorax showing a double lung point. The double lung point is explained by the fact that the air is not free in the pleural space but forms a bulla surrounded by adherent pleural layers. In this case, the ultrasound examination could be confounding and the clinician should be aware of it. This phenomenon is quite rare in the juvenile spontaneous pneumothorax, being more frequent in case of secondary pneumothorax.
Abstract: Over the last decade, the use of ultrasound as a technique to look for pneumothorax has rapidly evolved. This review aims to analyze and synthesize current knowledge on lung ultrasound targeted at the diagnosis of pneumothorax. The technique and its usefulness in different scenarios are explained, and its merits over conventional radiology are highlighted.
Abstract: Treatment of nontraumatic cardiac arrest in the hospital setting depends on the recognition of heart rhythm and differential diagnosis of the underlying condition while maintaining a constant oxygenated blood flow by ventilation and chest compression. Diagnostic process relies only on patient's history, physical findings, and active electrocardiography. Ultrasound is not currently scheduled in the resuscitation guidelines. Nevertheless, the use of real-time ultrasonography during resuscitation has the potential to improve diagnostic accuracy and allows the physician a greater confidence in deciding aggressive life-saving therapeutic procedures. This article reviews the current opinions and literature about the use of emergency ultrasound during resuscitation of nontraumatic cardiac arrest. Cardiac and lung ultrasound have a great potential in identifying the reversible mechanical causes of pulseless electrical activity or asystole. Brief examination of the heart can even detect a real cardiac standstill regardless of electrical activity displayed on the monitor, which is a crucial prognostic indicator. Moreover, ultrasound can be useful to verify and monitor the tracheal tube placement. Limitation to the use of ultrasound is the need to minimize the no-flow intervals during mechanical cardiopulmonary resuscitation. However, real-time ultrasound can be successfully applied during brief pausing of chest compression and first pulse-check. Finally, lung sonographic examination targeted to the detection of signs of pulmonary congestion has the potential to allow hemodynamic noninvasive monitoring before and after mechanical cardiopulmonary maneuvers.
Abstract: Iatrogenic ureteral injury is an uncommon but dangerous complication of abdominal and pelvic surgery. When recognized and promptly treated, most ureteral lesions heal without sequelae. Instead, undetected injuries may last for a prolonged period of time since symptoms and signs are usually subtle and nonspecific, even if evolution may be life threatening. In doubtful cases the diagnostic role of modern multiphase helical computed tomography is crucial. We describe the late presentation in the Emergency Department of a case of double left ureteral injury after abdominal surgery, and illustrate the appearance of the lesions at computerized tomography.
Abstract:
Purposes
B-lines are vertical echogenic artifacts seen on lung ultrasound that allow bedside diagnosis of pulmonary edema. The BLUE protocol, published by Lichtenstein and Mezière, suggests that cardiogenic pulmonary edema is sufficiently ruled out in the ICU setting when B-lines are not predominant in the anterior chest (the B-profile). Our analysis sought to evaluate the sensitivity of the B-profile for ruling out pulmonary edema in the ED patient population.
Methods
The ultrasound lung scans of patients with confirmed official diagnoses of acute decompensated heart failure (ADHF) from two ED databases were retrospectively analyzed. 170 acutely dyspneic patients had complete studies (130 from one database and 40 from the other). The scans were reviewed using the B-profile definition for ruling out pulmonary edema and comparing that to an alternate scanning protocol that includes ultrasound evaluation of the lateral and anterior chest.
Results
Of the 170 ED patients with ADHF diagnoses, the B-profile missed 16.5% (n = 28) for a sensitivity of 83.5% (95% CI 77â89%). These 28 patients did not show anterior bilateral B-lines that fit the criteria for positive under the BLUE protocol. Moreover, 25% (7/28) of these missed patients had only lateral B-lines on their lung scans and B-lines would have been detected only by including scans of the lateral zones.
Conclusions
Limiting the sonographic lung examination to the anterior chest areas only will miss cases of ADHF in the dyspneic ED patients. The BLUE protocol (B-profile) may need to be modified to include examination of the lateral chest as necessary for ED patients with ADHF.
Abstract: During the last few years, a growing number of studies have shown the accuracy of lung ultrasound in the diagnosis of pulmonary diseases. The latest developments in lung ultrasound are not because of technological advance, but are based on new applications and discovering the meanings of sonographic artifacts. Real-time sonography of the lung in the emergency department saves time and cost, providing immediate information to the clinician, relying on very easy-to-acquire data. The bedside sonographic recognition of pulmonary diseases practically guides management and reduces the amount of negative radiologic image testings. This review describes some innovative practical applications of B-mode lung ultrasound in the diagnosis of alveolar consolidations and interstitial syndrome in the emergency department.
Abstract: First described by Klemperer and Rabin in 1931, solitary fibrous tumour of the pleura (SFTP) is a mesenchymal tumour that tends to involve
the pleura, although it has also been described in other thoracic areas (mediastinum, pericardium and pulmonary parenchyma) and in extrathoracic
sites (meninges, epiglottis, salivary glands, thyroid, kidneys and breast). SFTP usually presents as a peripheral mass abutting the
pleural surface, to which it is attached by a broad base or, more frequently, by a pedicle that allows it to be mobile within the pleural cavity.
A precise preoperative diagnosis can be arrived at with a cutting-needle biopsy, although most cases are diagnosed with postoperative histology
and immunohistochemical analysis of the dissected sample. SFTP, owing to its large size or unusual locations (paraspinal, paramediastinal,
intrafissural), can pose interpretation problems or, indeed, point towards a diagnosis of diseases of a totally different nature.
We present computed tomography (CT) features of SFTP in patients who had had surgical resection in order to discover any specific CT
findings that might help in the diagnosis of these tumors
Abstract: Solitary fibrous tumor of the pleura (SFTP) is a mesenchymal tumor that tends to involve the pleura, and is also described in other thoracic and extrathoracic sites. SFTP usually presents as a peripheral mass abutting the pleural surface, to which it is attached by a broad base or by a pedicle that allows it to be mobile. SFTPs exist in benign and malignant forms. A precise pre-operative diagnosis can be arrived at with a cutting-needle biopsy, although most cases are diagnosed with postoperative histology and immunohistochemical analysis. In this pictorial essay, we review a large series of cases, with emphasis on the radiographic appearance of these lesions and their findings from computed tomography, magnetic resonance imaging, ultrasonography and positron emission tomography.
Abstract: A 50-year-old woman presented to our emergency department complaining of recurrent epigastric stabbing pain on eating of 1 month duration. She had a history of morbid obesity treated 13 years before with laparoscopic vertical banded gastroplasty (VBG). Diagnosis was made by radiology, after upper gastrointestinal series and abdominal unenhanced computed tomography. These demonstrated intragastric band migration, with outlet stenosis of narrowed stomach. Vertical banded gastroplasty is a miniinvasive approach that gives the benefits of shorter hospital stay, less postoperative pain, and quicker functional recovery. However, many complications are known and require recognition to be appropriately treated. In our case, the history and clinical presentation led to a high suspicion of intraabdominal pathology due to postoperative complication. Radiologic upper gastrointestinal investigation and computed tomography findings were then decisive to detect the intragastric band migration.
Abstract: This review discusses the usefulness of bedside lung ultrasound in the diagnostic distinction between the various causes of acute dyspnoea in the emergency department, with special attention to the differential diagnosis of pulmonary oedema and exacerbation of chronic obstructive pulmonary disease (COPD). This is made possible by using mid- to low-end scanners and simple acquisition techniques accessible to both radiologists and clinicians. Major advantages include ready availability at the bedside, the absence of ionising radiation, high reproducibility and cost efficiency. The technique is based on the recognition and analysis of sonographic artefacts rather than direct visualisation of the pulmonary structures. These artefacts are caused by the interaction of water-rich structures and air, called comet tails or B-lines. When such artefacts are widely detected on anterolateral transthoracic lung scans, diffuse alveolar-interstitial syndrome can be diagnosed, which is often a sign of acute pulmonary oedema. This condition rules out exacerbation of COPD as the main cause of acute dyspnoea.
Abstract: We present the cases of 23- and 38-year-old healthy patients with clinical diagnosis of acute measles who experienced shortness of breath on exertion with nonproductive cough and showed signs of mild respiratory failure at presentation in the emergency department (ED) but with normal chest radiograph and auscultation. In both cases, bedside ultrasound of the lung showed the appearance of signs of interstitial diffuse involvement with vertical B lines spread all over the lateral and posterior chest wall. This sonographic pattern is typical of the interstitial involvement during acute viral pneumonitis that can be missed by physical examination and chest radiography. Even without radiologic infiltrates and pulmonary sounds, based on sonographic and arterial gas signs, a diagnosis of measles pneumonitis was done and patients admitted to the ward for close follow-up and supportive care. We hypothesize a new diagnostic role of bedside lung sonography in screening patients presenting to the ED with initial lung involvement in measles who warrant close follow-up and hospital admission.
Abstract: The evaluation of pleuritic pain in the emergency setting is a diagnostic challenge. Most patients are discharged from the Emergency Department (ED) with a diagnosis of chest wall pain not otherwise specified. It is important to rule out possible sources of acute pleuritic pain, like pulmonary embolism, pneumonia, lung cancer, and pneumothorax. Clinical examination, plain film radiography of the chest, and other routine investigations may be inadequate to make the correct diagnosis. In this setting, another bedside test to aid diagnosis would be useful. ED bedside lung ultrasound is a novel technique for the diagnosis of lung diseases. We report on 5 patients who presented to our ED complaining of pleuritic pain, few other symptoms, and negative routine investigations, in whom bedside lung ultrasound aided in making the diagnosis.
Abstract: Diffuse comet-tail B-line artifacts in lung ultrasound are a sign of alveolar-interstitial syndrome, but isolated transthoracic scans positive for B-lines (multiple B lines or B+) could be detected in other conditions. The aim was to assess the prevalence and distribution of this sonographic sign in patients with normal lung or isolated alveolar consolidation in chest radiography.
Abstract: The evaluation of pleuritic pain in the emergency department (ED) presents a considerable challenge for the attending physician. Chest radiography (CXR) is a basic test, but its sensitivity is low, and often more sophisticated imaging techniques are needed. Our aim is to assess the diagnostic value of bedside B-mode lung ultrasound (LUS) in the visualization of radio-occult pulmonary lesions. Forty-nine patients complaining of pleuritic pain with negative CXR were prospectively studied by LUS. Detection of at least one of the following sonographic signs in the painful thoracic area was considered diagnostic: (i) the absence of pleural sliding; (ii) the focal alveolar-interstitial syndrome (AIS), defined by multiple artifacts B-line; (iii) the peripheral alveolar consolidation (PAC), defined by hypoechoic subpleural images; and (iv) the pleural disruption with thickening and irregularity of the line, with or without localized effusion. The final diagnoses were confirmed by spiral CT scanning (n = 12) and follow-up (n = 37). Final diagnoses were chest wall pain (n = 30), pleuropneumonia (n = 14), pulmonary embolism (n = 4), lung metastasis (n = 1). In 18 patients of the group with pulmonary conditions, LUS showed signs of pleurisy. They were PAC (n = 12), AIS (n = 17), pleural disruption (n = 17). If any sign is considered, the sensitivity of LUS in the diagnosis of radio-occult lesions was 94.7%, specificity was 96.7%, positive and negative predictive values were 94.7% and 96.7%, respectively, and accuracy was 95.9%. In patients with pleuritic pain of unknown cause, real-time LUS enables the diagnosis of radio-occult lung and pleural lesions.
Abstract: Multiple artifacts B lines (B+) at transthoracic lung ultrasound have been proposed as a sonographic sign of pulmonary congestion. Our aim is to assess B+ clearance after medical treatment in acute decompensated heart failure (ADHF) and to compare the usefulness of sonography with other traditional tools in monitoring resolution of pulmonary congestion.
Abstract: This review discusses the usefulness of bedside lung ultrasound in the diagnostic distinction between different causes of acute dyspnea in the emergency setting, particularly focusing on differential diagnosis of pulmonary edema and exacerbation of chronic obstructive pulmonary disease (COPD). This is possible using a simple unit and easy-to-acquire technique performed by radiologists and clinicians. Major advantages include bedside availability, absence of radiation, high feasibility and reproducibility, and cost efficiency. The technique is based on analysis of sonographic artifacts instead of direct visualization of pulmonary structures. Artifacts are because of interactions between water-rich structures and air and are called "comet tails" or B lines. When such artifacts are widely detected on anterolateral transthoracic lung scans, we diagnose diffuse alveolar-interstitial syndrome, which is often a sign of acute pulmonary edema. This condition rules out exacerbation of COPD as the main cause of an acute dyspnea.
Abstract: Mesenteric panniculitis is a rare disease leading to recurrent acute abdominal pain, whose recognition is important to avoid any unwarranted aggressive surgery. A case of this condition is described. The patient, a 73-year-old man, attended our emergency room with acute abdominal pain, fever and prolonged partial thromboplastin time. He had a history of recurrent emergency department access and complained of the same rapidly reversible clinical picture. Findings at abdominal computed tomography and at diagnostic laparascopy (including histology of a biopsy) helped reach a correct diagnosis and treatment. In this brief report from literature analysis, we present diagnosis and treatment of mesenteric panniculitis from what is known so far. Finally, we briefly discuss some peculiar pathogenesis and hypothesis.
Abstract: To assess the potential of bedside lung ultrasound to diagnose the radiologic alveolar-interstitial syndrome (AIS) in patients admitted to an emergency medicine unit and to estimate the occurrence of ultrasound pattern of diffuse and multiple comet tail artifacts in diseases involving lung interstitium.
Abstract: We present and discuss the case of a man admitted to our emergency room because of severe hypercalcemia and renal failure with maintained diuresis. We diagnosed a relapse of sarcoidosis, manifesting as hypercalcemia and renal failure, based on a history of lung sarcoidosis. This is a rare complication of sarcoidosis, due to granulomatous production of vitamin D. This mechanism may have been exacerbated by exposure of sunlight. The initial treatment of the patient was directed towards lowering the circulating calcium level through hyperhydration and forced diuresis, with secondary control of granulomatous activity using corticosteroid therapy. The patient was discharged after 7 days with normal levels of serum calcium, urinary calcium excretion and serum creatinine. Recognition of this rare cause of hypercalcemia is a challenge for the emergency physician.
Abstract: Unilateral re-expansion pulmonary oedema is a rare threatening complication of the treatment of lung atelectasis, pleural effusion or pneumothorax, the pathogenesis of which is not completely known. The clinical picture varies considerably from asymptomatic radiological findings to dramatic respiratory failure with circulatory shock. There are few literature reports of the treatment of re-expansion pulmonary oedema with non-invasive continuous positive airway pressure. We present the case of a 75-year-old man who presented in our emergency room with a large left-sided spontaneous pneumothorax and developed severe respiratory failure and circulatory collapse after drainage via a chest tube. The diagnosis of unilateral re-expansion pulmonary oedema was made and he was successfully treated with non-invasive continuous positive airway pressure. Literature data about the aetiological and pathogenetic factors of the condition are also considered.
Abstract: This is a technical study to show the feasibility of a computer-controlled oral glucose tolerance test (OGTT) using a specific algorithm, consisting of an OGTT carried out while insulin is infused as required to keep glycaemia within the normal range (National Diabetes Data Group 1979 criteria). This technique allows (a) the amount of insulin (insulin area) required to maintain a normal glycaemic curve to be assessed, a parameter indicating the degree of insulin resistance; and (b) the unique parameter consisting of the insulin secretory response (C-peptide) to a normal glycaemic curve under the inhibitory feedback exerted by the insulin levels required to maintain normal glycaemia to be obtained. Preliminary results confirmed the feasibility of this approach by showing that during the test while the glycaemic area was kept normal the insulinaemic area (endogenous + infused insulin) increased markedly in obese (n = 8) and obese diabetic (n = 5) subjects compared with normal subjects (n = 6), with values of 145.10 +/- 26.71, 204.75 +/- 20.77 and 68.25 +/- 5.93 nmol l-1 min-1 respectively (P < 0.01 in both instances). In contrast, endogenous insulin secretion (C-peptide levels) remained almost unchanged. Compared with data in normal subjects, free fatty acid (FFA) values were basally elevated in the obese and obese diabetic patients, and underwent a smaller decrease during the test. The FFA areas were greater than normal in both groups of patients, suggesting that FFAs were not fully suppressible despite the highest possible insulin levels (higher insulin levels would produce hypoglycaemia). The computer-controlled OGTT might be useful for the metabolic study of patients in the clinical setting.
Abstract: Insulin Sensitivity Indices for glycemia [ISI(gly)] and blood FFA [ISI(ffa)] can be calculated with the formulas: ISI(gly) = 2/[(INSp x GLYp) + 1], and ISI(ffa) = 2/[(INSp x FFAp) + 1], where INSp, GLYp and FFAp = insulinemic, glycemic, and FFA areas during OGTT (75 g glucose) of the person under study, simplified by considering only data at 0 and 2 h (0-2 h areas), according to WHO criteria or, better, at 0, 1 and 2 h (0-1-2 h areas). Expressed as unit/ volume.h-1, 0-1-2 h area is equal to 1/2 value at 0 min + value at 1 h + 1/2 value at 2 h, while 0-2 h area is equal to value at 0 + value at 2 h. Instead of areas, basal levels can also be used. Basal levels and areas are expressed taking the mean normal value as unit, so that in normal subjects ISI(gly) and ISI(ffa) are always around 1, with maximal variations between 0 and 2. Each laboratory should have its normal reference values for basal levels and OGTT areas. However, reliable mean normal values were selected from literature. Based on meta-analysis of published data, ISI(gly) and ISI(ffa) were reduced in subjects who were overweight and/or IGT and in NIDDM patients and their relatives. Moreover, correlation of ISI(gly) with the euglycemic clamp data was significant. However, it should be stressed that the clamp procedure is performed under artificially induced steady-state whereas ISI(gly) and ISI(ffa) are obtained under rather physiological conditions, with hormonal and metabolic variables unmodified, thus being suitable to assess whole-body insulin sensitivity in the clinical setting.
Abstract: After having previously shown that some noninsulin-sensitive tissues (capillaries and optic nerve) phosphorylate glucose in a concentration-dependent manner through a glucokinase-like enzyme, here, we report data on glucose phosphorylation in rabbit lens and retina at various glucose concentrations (1, 5, 10, 25, 50, and 100 mmol/L). In the 3000 g supernatant of lens and retina homogenates from two separate groups of female albino rabbits ten animals in each group; 1.8-2.0 kg body weight; mean +/- SEM morning glycemia: 8.19 +/- 0.28 and 8.12 +/- 0.24 mmol/L, respectively) was assayed glucose phosphorylating activity (NADP reduction measured as change in optical density at 366 nm at pH 7.5). The enzyme activity did not reach the maximum at low glucose concentration (1 mmol/L), as it occurs in several tissues, but increased progressively in both tissues with the increase in glucose concentration. Values (mean +/- SEM) for lens were 0.197 +/- 0.031 nmol/min/mg protein at 1 mmol/L and 0.327 +/- 0.051 (the highest value) at 50 mmol/L glucose (+65.99%, p < 0.01; r = 0.31, p < 0.05). Values for retina were 36.02 +/- 2.12 at 1 mmol/L glucose and 42.48 +/- 2.79 (the highest value) at 25 mmol/L glucose (+17.93%, p < 0.001; r = 0.32, p < 0.05). These kinetic characteristics, somewhat reminiscent of those shown by hepatic glucokinase, are still more pronounced when we calculated the "glucokinase component," obtained by subtracting the activity at 1 mmol/L glucose (hexokinase component) from that at the highest glucose concentration (total glucose phosphorylating activity). In five rabbits of similar age and weight, with spontaneous hyperglycemia (mean +/- SEM morning glycemia: 11.71 +/- 0.60) glucose phosphorylation in the retina was lower than normal, value at pH 7.5 and 1 mmol/L glucose being 24.52 +/- 2.20 versus 36.02 +/- 2.12 of normal animals (-31.93%, p < 0.01). This, if occurs also in other tissues, could contribute to the hyperglycemia by reducing glucose utilization. In these animals, however, the glucose phosphorylating activity retained the responsivity to increasing glucose concentrations, with value at 100 mmol/L of 28.65 +/- 2.10, corresponding to + 16.84% over the value at 1 mmol/L (p < 0.01). Therefore, the actual glucose phosphorylation in the retina of these animals would depend both upon the enzyme level (which is reduced) and glucose concentration (which is increased). Due to the in vivo inhibition of the hexokinase component by glucose 6-phosphate, the glucokinase component in retina and lens may be predominant in vivo, making the stimulating effect of hyperglycemia much more important than it would appear from our in vitro data. This might play a role in the chronic diabetic complications.
Abstract: We report the case of a 22-year-old obese woman with severe protein S deficiency, probably genetic in nature, associated with recurrent venous thrombosis. Protein S deficiency is a rather rare disease: it may be an inherited, either homozygous (purpura fulminans at neonatal age), heterozygous, or acquired disorder. The thrombophilic state may be manifested as deep vein thrombosis or thrombophlebitis of the superficial veins with a high risk of pulmonary embolism in the young, and it is often exacerbated by pregnancy. In our case, the presenting event, bilateral deep venous (iliac-femoral) thrombosis complicated by disseminated intravascular coagulation, had occurred when the patient was 13 years old. We started long-term therapy with oral coagulants, i.e. warfarin even if the latter may cause skin necrosis ("warfarin dermatitis") in some patients with protein S deficiency. The clinician must consider protein S deficiency in cases of recurrent thrombosis, particularly in young patients: the importance of early implementation of long-term preventive therapy should not be underestimated.
Abstract: We investigated glucose phosphorylation at various concentrations of glucose (1, 5, 10, 25, 50, 100 mmol/liter) in rabbit optic nerve. In the 3000 g supernatant of whole rabbit optic nerve homogenates from female albino rabbits (n = 10, 1.8-2.0 kg body weight, mean +/- SEM morning glycemia: 8.25 +/- 0.29 mmol/liter), the glucose phosphorylating activity (NADP reduction measured as change in optical density at 366 nm at pH 7.5) increased progressively with the increase in glucose concentration (r = 0.89; P < 0.05) and approached the maximum at a very high glucose level (100 mmol/liter), with values (mean +/- SEM) of 8.75 +/- 0.97 nanomol/min/mg protein and 11.57 +/- 1.15 at 1 and 100 mmol/liter glucose, respectively (+32.23%; P < 0.01). At a more alkaline pH (8.2; n = 5, mean +/- SEM morning glycemia: 8.83 +/- 0.07 mmol/liter) glucose phosphorylation was higher than at pH 7.5 and retained the glucose concentration dependence (r = 0.95, P < 0.01). These kinetic characteristics are reminiscent of those of the low-affinity enzyme glucokinase, which is typically present in the liver. By subtracting the activity at 1 mmol/liter glucose from that at higher glucose concentrations, we calculated the "glucokinase component," forms the "total" glucose phosphorylating activity. In five rabbits (of similar age and weight) with spontaneous hyperglycemia (mean +/- SEM: 11.71 +/- 0.60 mmol/liter), the optic nerve glucose phosphorylating activity was lower (value at 1 mmol/liter glucose: 5.42 +/- 1.31, -38.06%, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: We have studied glucose phosphorylation at increasing glucose concentrations (1, 5, 10, 25, 50, and 100 mmol/liter) in capillaries of the choroidocapillary lamina from the eye of normal female albino rabbits (n = 10; body wt 1800-2000 g; mean +/- SEM morning glycemia: 147.77 +/- 4.02 mg/dl) and from the eye of spontaneously hyperglycemic rabbits (n = 5, body wt 1800-2000 g, mean +/- SEM morning glycemia; 211.00 +/- 10.76 mg/dl). In the 3000g supernatant of capillary homogenates, the glucose phosphorylating activity (NADP reduction measured as optical density change at 366 nm at pH 7.5) increased progressively with the rise of glucose concentration (r = 0.36; P < 0.05), approaching the peak at high glucose level (25 mmol/liter), with values ranging from 5.32 +/- 0.46 (SEM) nmol/min/mg protein to 7.14 +/- 0.74 (+34.21%, P < 0.01). When measured at a more alkaline pH (8.2) the glucose phosphorylation was higher than at pH 7.5 and retained the responsiveness to increasing glucose concentrations. These kinetic characteristics differ from those seen in most tissues and are somewhat reminiscent of those shown by hepatic glucokinase. Indeed, by subtracting the activity at 1 mmol/liter glucose from that at higher glucose concentrations, we calculated the "glucokinase component" which together with the "hexokinase component" form the total glucose phosphorylating activity. Glucose phosphorylation in capillaries from spontaneously hyperglycemic rabbits was lower than normal (values: 3.66 +/- 0.31 vs 5.32 +/- 0.46 of the normal rabbits; -31.20%; P < 0.05). This could contribute to the hyperglycemia by reducing glucose utilization. However, in these animals the enzyme activity retained the responsivity to increasing glucose concentrations (r = 0.41, P < 0.05). Therefore, the actual capillary glucose phosphorylation in these animals would depend upon both the enzyme level (which is reduced) and the glucose concentration (which is increased). Due to the in vivo inhibition of the hexokinase component, the glucokinase component may be predominant in vivo, making the stimulating effects of hyperglycemia much more pronounced than it would appear from our data in vitro. This may lead to glucose overutilization. These kinetic characteristics of glucose phosphorylation in capillaries might be relevant to the mechanisms leading to diabetic microangiopathy.
Abstract: Glucose phosphorylation was studied in a pure capillary preparation obtained from the rete mirabile of the eel swimbladder. In the 3000g supernatant of capillary homogenates, the glucose phosphorylating activity did not reach the maximum at low glucose concentration (1 mmole/liter), as it occurs in most tissues, but increased with the increase in glucose concentration and approached the maximum at very high (300 mmole/liter) glucose levels, with values (mean +/- SEM, n = 10) of 5.85 +/- 0.94 nmole.min-1.mg-1 protein and 19.97 +/- 1.89 at 1 and 300 mmole/liter glucose, respectively. The apparent Km value for glucose was about 50 mmole/liter, i.e., at supraphysiological glucose concentration, like the enzyme glucokinase, typically present in the liver but absent from most other tissues. This new enzyme did not phosphorylate fructose (similar to glucokinase from liver, which is rather specific for glucose) but was not inhibited by N-acetyl-glucosamine (in contrast to hepatic glucokinase). Thus, capillaries phosphorylate glucose in a concentration-dependent manner, which suggests that they are equipped with a glucokinase-like enzyme. This may explain the reported increase in glucose uptake during capillary exposure to high glucose concentrations and would suggest that the hyperglycemia of the diabetic state may be associated with increased glucose utilization, which may play a role in the development of microangiopathy.
Abstract: An automatic glycemic control system (Beta-like, Esaote) was used to calculate the insulin area (IA) required to keep glycemia within the normal range during OGTT (using NDDG criteria). IA was calculated by adding total endogenous insulin to insulin infused by the Betalike system (Actrapid HM, Novo). During the test, glycemia was obliged to follow a mean normal curve using an insulin infusion according to a special algorithm which automatically adapted to individual parameter variations during the different stages of OGTT. Fourteen blood samples were collected to assay metabolites (glucose, NEFA, lactate and alanine) and hormones (insulin, C peptide, glucagon). Data on insulinemia and glycemia were used to calculate the respective areas under the total and incremental curve (IA expressed in UL-1 min-1 and GA expressed in mM.L-1.min-1); an insulin resistance index was then calculated (total and incremental) using the following formula: IA/(normal GA/patient GA). This test allows us: a) to evaluate the insulin secretory response to a standard glycemic stimulus represented by a glycemic curve within the normal range; b) to calculate the quantity of insulin necessary to maintain the glycemic curve within the normal range; c) to evaluate the body's total insulin resistance according to an index calculated on the basis of the insulin area required; d) to compare the calculated insulin resistance index with NEFA and glucagon data obtained during the test; e) to identify the exact evolution of these events over time during OGTT.
Abstract: We tested the in vitro effects of various glucose concentrations on the activity of hepatic pyruvate kinase, assayed at subsaturating, near physiological concentration (0.20 mmol/l) of the substrate phosphoenolpyruvate, to detect the "active" form of the enzyme. A 10-min incubation of mouse liver slices (n = 18) with increasing glucose concentrations (5, 10 and 20 mmol/l) resulted in a significant (p less than 0.01), progressive pyruvate kinase inhibition of 15, 28 and 41%, respectively. Similar data were obtained by incubating mouse liver homogenates (n = 7) with glucose, although with this material (which was supplemented with the pyruvate kinase activator fructose-1,6-diphosphate) the inhibition at the highest glucose concentration used was lower (24%, p less than 0.02). Addition of 10 nmol/l insulin during slice incubation (n = 8) prevented by 98% and 69% the inhibition exerted by 10 and 20 mmol/l glucose, respectively. Insulin alone was without effect on the enzyme activity. Glucose might inhibit pyruvate kinase by competing with the activator fructose-1,6-diphosphate. Insulin might overcome the glucose effect by activating pyruvate kinase through the known mechanism of enzyme dephosphorylation. Thus, in decompensated diabetes the high level of blood glucose may contribute, together with the counterregulatory hormones, to inhibit hepatic pyruvate kinase and therefore to stimulate gluconeogenesis.
