[Christmas article: Goose breast caused by unusual circumstances].

This case report investigate a 61-year-old healthy man who, during a Christmas goose-shooting, got repeated punches on the right breast region, owing to a defective shotgun stock. The initial suggilations and haematomas disappeared in three weeks, but after three months a tender enlargement of the periareolar area developed. Mammography and sonography showed typical right gynaecomastia. History, andrologial examination and biochemistry disclosed no explanation. It was concluded that a traumatic aetiology of the gynaecomastia was most likely. During the next year, the clinical signs regressed somewhat, but control sonography showed leftovers of ductal tissue, and the bird shooter has become reconciled with his "goose breast".

Determination of hepatic clearance by derivations of the indocyanine green retention test in cirrhosis.

BACKGROUND AND AIM: The study was undertaken in order to compare single injection indocyanine green (ICG)-clearances with the steady-state ICG-clearance (ICGCl ) in patients with cirrhosis in order to assess the most accurate estimate for ICG-clearance and to relate the ICG-clearances to established indicators of liver dysfunction. METHODS: Thirty-eight patients (male 29) with cirrhosis (Child-Turcotte class A 8, class B 21, and class C 9) were studied during a hemodynamic investigation. A single injection of ICG was followed by blood samples for 5, 10, 15, and 20 min. The dose/plasma area clearance (ClA ) and plasma volume · initial slope clearance (ClPV ) were determined and compared with the steady-state infusion/plasma concentration ratio clearance (ICGCl ). RESULTS: The ClA (310; 214; 502 mL/min) and ClPV (294; 164; 481 mL/min) correlated closely with ICGCl (243; 120; 383 mL/min [median; interquartile range], R = 0.95-0.98, P < 0.000), but were significantly higher than ICGCl (P < 0.001). All three clearance measures correlated significantly with biochemical and hemodynamic variables of liver dysfunction (P < 0.05-0.000). All three ICG-clearances showed significantly lower values in patients with ascites compared to those without, and lower ICG-clearance values were present in patients with esophageal varices compared to those without (P < 0.05-0.002). CONCLUSION: Single injection markers (ClA and ClPV ) of the steady-state ICG-clearance as derived from the ICG-retention curve and the plasma volume correlate with ICGCl and established variables of portal hypertension and liver cell bile excretory dysfunction. Therefore, these markers can safely replace the more costly ICGCl .

Neuro-SPECT: On the development and function of brain emission tomography in the Copenhagen area.

This review describes the development of single-photon emission tomography (SPECT) in the Copenhagen area under the leadership of the internationally renown scientist, Niels A. Lassen, and the history leading up to construction of the tomograph. Measurements of global cerebral blood flow (CBF) in the 1940s and 1950s were performed by Kety & Schmidt and Lassen & Munck. Determination of regional cerebral blood flow (rCBF) by intra-arterial injection of 133 Xe and measurement with a 254-multicrystal scintillation detector and a computer system was a major step forward in the study of physiology and pathophysiology of cortical cerebral blood flow. Tomography with radioisotope ligands, including non-invasive administration, was advanced in different centres during the 1970s. An emission tomograph, the Tomomatic 64, was developed as a result of a multidisciplinary Danish and international collaboration. It was the first emission tomograph to provide dynamic data that could produce cross-sectional rCBF images. The present description of the construction and function of the Tomomatic 64 includes comparison with other contemporary and later brain-dedicated SPECT systems. Basic and clinical application of the Tomomatic 64 in Copenhagen resulted in several hundred important scientific publications and improved diagnostics for patients with a variety of neurological disorders. It is concluded that the development of the Tomomatic 64 was a major step forward in the study and examination of rCBF and brain function related to several brain disorders, in addition to vascular diseases.

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on blood volume distribution in patients with cirrhosis.

BACKGROUND: Cirrhosis is accompanied by portal hypertension with splanchnic and systemic arterial vasodilation, and central hypovolaemia. A transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension, but also causes major haemodynamic changes. AIMS: To investigate effects of TIPS on regional blood volume distribution, and systemic haemodynamics. METHODS: Thirteen cirrhotic patients had their regional blood volume distribution determined with gamma-camera technique before and after TIPS. Additionally, we measured systemic haemodynamics during liver vein and right heart catheterization. Central and arterial blood volume (CBV) and cardiac output (CO) were determined with indicator dilution technique. RESULTS: After TIPS, the thoracic blood volume increased (+10.4% of total blood volume (TBV), p<0.01), whereas the splanchnic blood volume decreased (-11.9% of TBV, p<0.001). CO increased (+22%, p<0.0001), and systemic vascular resistance decreased (-26%, p<0.001), whereas CBV did not change. Finally, right atrial pressure and mean pulmonary artery pressure increased after TIPS (+50%, p<0.005; +40%, p<0.05, respectively). CONCLUSIONS: TIPS restores central hypovolaemia by an increase in thoracic blood volume and alleviates splanchnic vascular congestion. In contrast, CBV seems unaltered. The improvement in central hypovolaemia is therefore based on an increase in thoracic blood volume that includes both the central venous and arterial blood volume. This is supported by an increase in preload, combined with a decrease in afterload.

Gamma-variate plasma clearance versus urinary plasma clearance of 51 Cr-EDTA in patients with cirrhosis with and without fluid retention.

In patients with fluid retention, the plasma clearance of 51 Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of 51 Cr-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of 51 Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu  = ΔCl) was mean -0·6 ml min-1  1·73 m-2 . In patients with ascites, ΔCl was significantly higher (11·8 ml min-1  1·73 m-2 , P<0·0001), but this value was lower than Clexp - Clu (17·5 mL min-1  1·73 m-2 , P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Clgv and Clexp overestimates GFR substantially, but the overestimation is smaller with Clgv . Although Clu may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.

Red blood cell sodium transport in patients with cirrhosis.

Patients with advanced cirrhosis have abnormal sodium homoeostasis. The study was undertaken to quantify the sodium transport across the plasma membrane of red blood cells (RBC) in patients with cirrhosis. RBC efflux and influx of sodium were studied in vitro with tracer (22) Na(+) according to linear kinetics in 24 patients with cirrhosis and 14 healthy controls. The sodium efflux was modified by ouabain (O), furosemide (F) and a combination of O and F (O + F). RBC sodium was significantly decreased (4·6 versus control 6·3 mmol l(-1) , P<0·001) and directly related to serum sodium (r = 0·57, P<0·05). The RBC fractional sodium efflux was higher in patients with cirrhosis (+46%, P<0·01) compared to controls. Inhibition in both high (145 mmol l(-1) )- and low (120 mmol l(-1) )-sodium buffers showed that the F-insensitive sodium efflux was twice as high in cirrhosis as in controls (P = 0·03-0·007), especially the O-sensitive, F-insensitive efflux was increased (+ 225%, P = 0·01-0·006). Fractional F-sensitive transport was normal in cirrhosis. RBC sodium influx was largely normal in cirrhosis. In conclusion, RBC sodium content is reduced in patients with cirrhosis with a direct relation to serum sodium. Increased RBC sodium efflux is especially related to ouabain-sensitive, furosemide-insensitive transport and thus most likely due to upregulated activity of the sodium-potassium pump. The study gives no evidence to an altered intracellular/extracellular sodium ratio or to a reduced fractional furosemide-sensitive sodium transport in cirrhosis.

Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction.

PURPOSE: Acid-base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation. METHODS: A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study. RESULTS: Hyperventilatory hypocapnia was present in all patients with cirrhosis and progressed from Child class A to C (P<0.01). Arterial pH increased significantly from class A to C (P<0.001) and was correlated inversely to the mean arterial blood pressure (r=-0.30, P<0.02), systemic vascular resistance (r=-0.25, P<0.05), indocyanine green clearance (r=-0.37, P<0.005), and serum sodium (r=-0.38, P<0.002). Metabolic compensation was shown by a reduced standard base excess in all patients (P<0.001). Standard base excess contained elements related to changes in serum albumin, water dilution, and effects of unidentified ions (all P<0.001). A significant hepatic component in the acid-base disturbances could not be identified. CONCLUSION: Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes alterations in serum albumin and water retention that may result in a delicate acid-base balance in these patients.

Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention.

BACKGROUND AND AIM: In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. MATERIAL AND METHODS: A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. RESULTS: In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 mL/min/1.73 m(2). In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m(2), p < 0.0001). ClΔ increased with lower values of GFR (r = - 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. CONCLUSION: In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention.

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.

Assessment of in situ adipose tissue inflammation by microdialysis.

BACKGROUND: Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore investigated the utility of microdialysis to study in situ AT interstitial inflammatory protein levels. MATERIAL AND METHODS: Abdominal subcutaneous AT microdialysis was performed in six healthy men, six HIV-infected men with lipodystrophy and six without lipodystrophy using the internal references (51) Cr-EDTA and (125) I-human serum albumin. We measured 41 inflammatory proteins in microdialysis samples by Luminex technology, as well as systemic levels in 14 subjects. Furthermore, in vitro studies of the internal reference technique for microdialysis recovery of inflammatory proteins were made. RESULTS: We detected in situ AT interstitial levels of 14 inflammatory proteins by microdialysis, while the 27 other inflammatory proteins assessed were only detected sporadically. Initial levels of IL-6 and IL-8 were undetectable. Insertion trauma affected IL-1α, IL-6, IL-8, monocyte chemotactic factor (MCP)-1, IP-10, G-CSF, growth-related oncogene (GRO), macrophage-derived chemokine (MDC) and macrophage inflammatory protein (MIP)-1ß levels, while fibroblast growth factor (FGF)-2 was not affected. Systemic and AT interstitial levels were poorly correlated. The microdialysis recovery of smaller proteins was higher than for larger, and the internal references improved microdialysis by accounting for variation in perfusion across the membrane. CONCLUSION: Interstitial inflammatory proteins can be sampled in situ using microdialysis. Use of internal references improves the microdialysis technique. However, insertion trauma hampers the use of microdialysis to study AT inflammatory levels, except for FGF-2. Still, microdialysis gives unique insight to in situ AT interstitial concentrations.

Extrahepatic complications to cirrhosis and portal hypertension: haemodynamic and homeostatic aspects.

In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. As a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs, antibiotics, drugs with specific effects on fibrogenesis and inflammation, and drugs that target specific receptors.

A century of indicator dilution technique.

This review imparts the history and the present status of the indicator dilution technique with quantitative bolus injection. The first report on flow measurement with this technique appeared 100 years ago. In 1928, the use of intravascular dyes made possible a widespread application in animals and human during the next decades. Multiple indicators, radioactive tracers, inlet-outlet detection and residue detection were introduced in the 1950s and 1960s, and refined along with the development of indicator kinetics. From the 1970s, a wide clinical use in the study of heart, brain, lungs, liver and kidneys developed, and powerful computers in the 1980s and 1990s accorded the technique a new dimension. Today, the indicator dilution technique, on one hand, is applied in the same way as 100 years ago, on the other hand it forms the basis of quantitative SPECT, positron emission tomography, and dynamic MR scans. The technique still undergoes refinement and elaboration as a lasting concept with a high potential for further development.

One-sample determination of glomerular filtration rate (GFR) in children. An evaluation based on 75 consecutive patients.

BACKGROUND AND AIM: From a clinical point of view determination of glomerular filtration rate (clearance) is important. The aim of the present study was to compare the one-sample clearance to reference multiple-sample (51)Cr-EDTA clearance in consecutively referred children suspected of or with established nephro-urological disorders. MATERIAL AND METHODS: A total of 75 children, age ½-13 years, received a quantitative intravenous injection of (51)Cr-EDTA followed by six plasma samples 10-120 min after injection. The multiple-sample clearance was measured as injected dose relative to the area under the plasma radioactivity curve. The one-sample clearance was determined from a single plasma sample collected at 60, 90 or 120 min after injection according to the one-pool method. RESULTS: The overall accuracy of one-sample clearance was excellent with mean numeric difference to the reference value of 0.7-1.7 mL/min. In 64 children, the one-sample clearance was within ± 4 mL/min of the multiple-sample value. However, in 11 children the numeric difference exceeded 4 mL/min (4.4-19.5). Analysis of age, body size, distribution volume, indicator retention time, clearance level, curve fitting, and sampling time could not explain the observed large difference between one-sample and multiple-sample clearance in these 15% of the children. CONCLUSION: In the majority of children there is an excellent agreement between one-sample clearance and multiple-sample clearance. However, unexpectedly in a small fraction (15%) larger discrepancies are found. If an accurate clearance value is essential a multiple-sample determination should be performed.

(99m) Tc-labelled human serum albumin cannot replace (125) I-labelled human serum albumin to determine plasma volume in patients with liver disease.

BACKGROUND AND AIMS: Determination of plasma volume (PV) is important in several clinical situations. Thus, patients with liver disease often have augmented PV as part of their sodium-water retention. This study was undertaken to compare PV determination by two indicators: technetium-labelled human serum albumin ((99m) Tc-HSA) and iodine-labelled human serum albumin ((125) I-HSA), as the former may have advantages at repeated measurements and the latter is the classical gold standard. STUDY POPULATION AND METHODS: In 88 patients, (64 with liver disease, mainly cirrhosis, and 24 patients without liver disease), simultaneous measurements of PV were taken with (99m) Tc-HSA and (125) I-HSA after 1 h in the supine position. Blood samples were obtained before and 10 min after quantitative injection of the two indicators. In a subset of patients (n = 32), the measurements were repeated within 1 h. RESULTS: In all patients, a close correlation was present between PV determined by the two indicators (r = 0·89, P<0·0001). In all, but twelve patients, a higher PV was obtained with (99m) Tc-HSA compared with (125) I-HSA (P<0·0001). PV determined with (99m) Tc-HSA exceeded PV determined with (125) I-HSA by 367 ml (5·2 ml kg(-1) ) in liver patients as compared to 260 ml (3·5 ml kg(-1) ) in patients without liver disease (P<0·05). The precision of repeated PV determination was 1·75% (coefficient of variation) with (99m) Tc-HSA and 1·71% with (125) I-HSA (ns), and similar values were found in patients with and without liver disease. CONCLUSION: The study demonstrates that (99m) Tc-HSA has the same precision as that of (125) I-HSA. However, especially in patients with liver disease, (99m) Tc-HSA consistently overestimates the PV, most likely owing to indicator heterogeneity with subsequent fast removal from the circulating medium with a higher volume of distribution as the outcome.

Different injection techniques in the assessment of central haemodynamics in patients with cirrhosis.

OBJECTIVE: Patients with cirrhosis often present with an abnormal distribution of blood volume with a reduced central blood volume (CBV) and central circulation time (CCT). In this group of patients it is important to determine the central haemodynamics as accurately as possible. The purpose of the present study was to compare an alternative injection technique by injecting technetium-labelled human serum albumin ((99m)Tc-HSA) from a deposit within the catheter lumen with the conventional injection technique by injecting iodine-labelled human serum albumin ((125)I-HSA) directly from a syringe. MATERIALS AND METHODS: In 192 patients with cirrhosis, CCT, CBV, and cardiac output (CO) were determined according to kinetic principles. Injection of the two radiolabelled HSA were performed simultaneously and followed by arterial blood sampling every second for the first minute. RESULTS: CCT was significantly shorter, and CO and CBV were significantly lower when determined by the alternative catheter deposit injection technique compared to determination by the traditional syringe deposit injection technique. The mean difference (bias) between CCT measured with the two methods was 0.38 s with limits of agreement ranging from - 0.83 s to 1.59 s. CONCLUSION: This study demonstrates that different injection techniques result in a minor but significant difference of the measured haemodynamics. When highly accurate measurements of the central haemodynamics are needed, we recommend using the alternative injection technique by injection of the indicator from a deposit within the catheter in order to reduce overestimation of CCT.

[The geese who flew home for Christmas]. / Gæssene, der ville hjem til jul

Gray geese of the bar-headed type (Anser indicus synonym: Eulabeia indica) perform trans-Himalayan migratory flight at extreme altitude. The physiological mechanisms include hyperventilation of cold air, increased lung diffusion capacity, proton gradients, high muscular temperature, amino acid mutation in haemoglobin and cytochrome oxidase, re-location of mitochondria, and extreme shifts in the oxy-haemoglobin dissociation curve due to Bohr- and temperature effects. The second annual migration takes place in late autumn, and the bar-headed geese come home in due time before Christmas.

Arterial pressure profile in patients with cirrhosis: Fourier analysis of arterial pulse in relation to pressure level, stroke volume, and severity of disease: on the reduction of afterload in the hyperdynamic syndrome.

OBJECTIVE: Patients with cirrhosis have cardiovascular dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyze the arterial pressure curve in relation to mean arterial pressure level, stroke volume, and severity of liver disease. MATERIALS AND METHODS: Forty-one patients with cirrhosis (Child-Turcotte classes A/B/C = 13/15/13) were studied during a hemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. We applied fast Fourier analysis to quantify the pressure components of the arterial curve, the harmonic Fourier coefficients (HFC). RESULTS: Mean arterial pressure was significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis versus controls. The HFC were significantly lower in patients with cirrhosis than in controls (-15 to -24%, p < 0.002), except for the fourth HFC, which was significantly increased (+28%, p < 0.02). In contrast to controls, which showed a highly significant effect of the level of arterial pressure on their HFC (p < 0.001), patients with cirrhosis did not show pressure or stroke volume dependence on their HFC, indicating an overall compliant and slow reflective arterial vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to the Child-Turcotte score (p < 0.05), and the HFC were borderline significantly related to this score (p = 0.07). CONCLUSIONS: The arterial pulsation in cirrhosis is qualitatively changed with reduced pulse reflections, which may protect against manifest cardiac failure in patients with advanced cirrhosis.