Degree Of Hypoalbuminemia Research Articles

HCV Relapse in Hemodialysis Egyptian Patients after Treatment with Direct Acting Antiviral Drugs

Abstract Background HCV infection is a major health problem in Egypt and unfortunately its prevalence is more in hemodialysis patients than general population, the advent of DAA led to increased rate of recovery and lower rates of side effects rather than standard interferon therapy, but relapse of HCV is not uncommon among these patients. Purpose: the aim of the current study was to assess the incidence of relapse among hemodialysis patients with HCV after treatment with different regimens DAAs and to identify the risk factors that might be associated with this relapse. Patients and Methods This case- control study was held in Shibin El-Kom Teaching Hospital, Menoufia, Egypt in the period between June 2015 and June 2020. The study included 250 hemodialysis patients with chronic HCV and previously treated with DAAs. Patient were classified according to DAA treatment response into patients with HCV relapse (186 patients) and a non-relapse group(64 patients).both groups were assessed regarding predictors and risk factors for HCV relapse. Results There were no statistically significant differences between both groups as regard age, sex, diabetes and ischemic heart disease. Hypertension was prevalent in non-relapse group with statistical significance(p = 0.0001). Sofosbuvir + Daclatasvir + Ribavirin regimen was the most commonly used regimen in relapse group (53.2%0 while Ritonavir/Ombitasvir/Paritaprevir+Ribavirin combination therapy was utilized more in non- relapse group, both showed statistical significance (p = 0.0001). HCV viral load, liver cirrhosis and hepatic focal lesion were predictors of treatment non-response. Conclusion In conclusion, multiple risk factors exist for HCV relapse after primary response to direct acting antiviral. These factors included hypertension, cirrhotic liver, presence of space occupying lesions, Sofosbuvir- based regimen, degree of hypoalbuminemia, degree of liver enzymes elevation, high bilirubin, and elevated alfa fetoprotein and viral load by HCV PCR. cirrhotic liver, space occupying lesions, sofosbuvir- based regimen and high alfa fetoprotein are the most significant predictors for HCV recurrence after primary response to direct acting antiviral in hemodialysis population.

Hypoalbuminemia in children with acute lymphoblastic leukemia: relation to asparaginase therapy and impact on high dose methotrexate elimination

PurposeHigh-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor.MethodsTo examine the impact of serum albumin we reviewed 325 HDMTX 5 g/m2 courses in a cohort of 51 children treated on the NOPHO ALL 2008 protocol, dividing the courses into four groups with different levels of baseline albumin (A < 25 g/L, B 25–29 g/L, C 30–34 g/L and D ≥ 35 g/L).ResultsHypoalbuminemia was present in 51% of the courses, mostly in the early phases of chemotherapy while asparaginase therapy is ongoing, and especially if given less than 2 weeks after a dose (78%). Hypoalbuminemia had a significant impact on the end-of-infusion serum MTX, depending on the degree of hypoalbuminemia: MTX > 150 µM was seen in 37%, 32%, 20% and 8% in groups A to D. Serum albumin < 30 g/L was significantly associated with low MTX clearance < 10 L/h/1.73m2 (78% vs. 36%) and high AUC ≥ 1000 µM*h (44% vs. 31%). The frequency of rising creatinine or prolonged elimination was not increased, but the risk of stomatitis was significantly higher (42% vs. 19%).ConclusionLow serum albumin is caused by concurrent asparaginase therapy and has a clinically significant impact on MTX disposition. Guidelines for administering HDMTX may need adjustment if serum albumin < 30 g/L, and, if possible, HDMTX courses should not be scheduled soon after asparaginase doses.

Pre-transplant hypoalbuminemia is not associated with worse short-term outcomes among kidney transplant recipients.

Serum albumin is an indicator of overall health status, but it remains unclear how pre-transplant hypoalbuminemia is associated with early post-transplant outcomes. This study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001-12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0g/dL), mild (≥3.5-<4.0g/dL), moderate (≥3.0-<3.5g/dL), or severe hypoalbuminemia (<3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re-operation related to post-transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post-transplant. A total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p<0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37-0.91; p=0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07-0.68; p=0.01) were associated with significantly lower rates of acute rejection within 6 months post-transplant. Patients with pre-transplant hypoalbuminemia have post-transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.

Liver: Function and dysfunction in COVID-19.

Context:COVID-19 is known to cause extrapulmonary manifestations, including gastrointestinal and abnormal liver functions. Multiple mechanisms have been proposed to explain the pathobiology of liver damage: ACE2 receptor cholangiocytes mediated systemic inflammation, cytokine storm, hyperinflammation, and hypoxic changes. This was a cross-sectional study done in Department of General Medicine,JJM Medical College Davangere between July and September 2020 of patients falling under Category B and Category C.Materials and Methods:The aim is to describe the clinical characteristics in patients of COVID-19 and investigate the gender difference with particular regard to liver impairment.Confirmation of COVID-19 positivity was based on RT-PCR for SARS-CoV-2 RNA. Laboratory investigations and clinical data was analyzed using SPSS Statistics 27.Results:The final study population consisted of 116 patients. On performing the Mann Whitney U test, adjusted P values reveal a significant difference in ALT (P = 0.0348), total bilirubin (P = 0.0012) and direct bilirubin (P = 0.0024). The degree of hypoalbuminemia in males was significantly higher than in females (P = 0.0075). Other biochemical parameters, however, did not show significant difference amongst patients based on gender. Acute kidney injury was the most prevalent condition, present in 67.2% of the patients. Other co-morbidities were diabetes mellites, chronic liver disease, hypertension, hepatitis B and C, and hypothyroidism.Conclusion:Ultrasonography of the abdomen is an essential investigation for all patients testing positive for COVID-19. Pre-existing disease may aggravate the viral hepatic injury, thereby worsening the clinical outcome. The profiles of liver toxicity of the drugs used in the treatment of COVID-19 also warrant watchful monitoring of liver function.

The influence of postoperative albumin levels on the outcome of cardiac surgery

BackgroundThe prognostic role of low postoperative serum albumin levels (SAL) after cardiac surgery (CS) remains unclear in patients with normal preoperative SAL. Our aim was to evaluate the influence of SAL on the outcome of CS.MethodsProspective observational study. Patients undergoing CS with normal preoperative SAL and nutritional status were included and classified into different subgroups based on SAL at 24 h after CS. We assessed outcomes (i.e., in-hospital mortality, postoperative complications and long-term survival) and results were analyzed among the different subgroups of SAL.ResultsWe included 2818 patients. Mean age was 64.5 ± 11.6 years and body mass index 28.0 ± 4.3Kg·m− 2. 5.8%(n = 162) of the patients had normal SAL levels(≥35 g·L− 1), 32.8%(n = 924) low deficit (30–34.9 g·L− 1), 44.3%(n = 1249) moderate deficit (25–29.9 g·L− 1), and 17.1%(n = 483) severe deficit(< 25 g·L− 1). Higher SAL after CS was associated with reduced in-hospital (OR:0.84;95% CI:0.80–0.84; P = 0.007) and long-term mortality (HR:0.85;95% CI:0.82–0.87;P < 0.001). Subgroups of patients with lower SAL showed worst long-term survival (5-year mortality:94.3% normal subgroup, 87.4% low, 83.1% moderate and 72.4% severe;P < 0.001). Multivariable analysis showed higher in-hospital mortality, sepsis, hemorrhage related complications, and ICU stay in subgroups of patients with lower SAL. Predictors of moderate and severe hypoalbuminemia were preoperative chronic kidney disease, previous CS, and longer cardiopulmonary bypass time.ConclusionsThe presence of postoperative hypoalbuminemia after CS is frequent and the degree of hypoalbuminemia may be associated with worst outcomes, even in the long-term scenario.

Should aspirin be used for primary prevention of thrombotic events in patients with membranous nephropathy?

Patients with nephrotic syndrome are at increased risk of thrombosis. The risk of venous thrombosis is particularly high in patients with nephrotic syndrome due to primary membranous nephropathy. Recent data provide evidence that these patients also have a high absolute risk of arterial thrombotic events, which is associated with the degree of hypoalbuminemia. In this commentary we discuss whether prophylactic aspirin therapy might be indicated in this patient population.

Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual's bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual's needs and adaptable to dynamic changes in health status and risk profile.

Reduced Serum Fetuin-A in Nephrotic Children: A Consequence of Proteinuria?

Background: The extracellular protein fetuin-A is a potent soluble inhibitor of calcification, and its deficiency has been associated with vascular calcification in dialysis patients. In proteinuric patients, significant urinary losses of fetuin-A may cause low serum fetuin-A levels. Methods: In a cross-sectional study, urinary/serum concentrations of fetuin-A were investigated in proteinuric children with glomerular diseases and preserved renal function (n = 58) in comparison to healthy controls (n = 246). Results: Mean fetuin-A serum concentrations were clearly reduced in children with nephrotic syndrome (0.25 ± 0.14 g/l, p < 0.001), slightly reduced in children with large proteinuria (0.39 ± 0.15 g/l, p < 0.05), and comparable to controls in those with mild proteinuria (0.45 ± 0.14 vs. 0.46 ± 0.12 g/l). Fetuin-A was positively correlated with serum protein (r = 0.58), albumin (r = 0.57), and calcium (r = 0.64), but negatively correlated with proteinuria (r = –0.41), albuminuria (r = –0.46), and urinary fetuin-A excretion (r = –0.48; each p < 0.001). The fractional excretion of fetuin-A was significantly associated with the degree of proteinuria and serum fetuin-A levels. However, the urinary loss of fetuin-A and albumin in nephrotic children differed by three orders of magnitude and the mean fractional excretion of fetuin-A was only 1/10 of that of albumin (0.016 ± 0.029 vs. 0.162 ± 0.403%; p < 0.001). Conclusions: Fetuin-A is clearly reduced in children with nephrotic syndrome and associated with the degree of hypoalbuminemia. This is due to urinary fetuin-A loss and/or reduced hepatic synthesis. Persistent fetuin-A deficiency may have an impact on cardiovascular morbidity in nephrotic children.

Preoperative albumin and surgical site identify surgical risk for major postoperative complications.

Although malnutrition contributes to morbidity, studies of pre- and postoperative nutrition often include well-nourished patients unlikely to benefit from therapy and usually do not stratify by the site of surgical pathology. This study evaluates whether perceived preoperative markers of nutritional status recorded in charts correlates with postoperative complications and resource use in patients who receive no preoperative nutrition support and reinterprets the results of several conflicting randomized, prospective studies in this context. This is a retrospective cohort study of 526 surgical patients who had preoperative serum albumin levels measured and were undergoing elective esophageal, gastric, pancreaticoduodenal, or colon surgery between 1992 and 1996 who could have received preoperative nutrition but did not. Most medical records contained inadequate analysis of preoperative nutritional status, but preoperative albumin correlated inversely with complications, length of stay, postoperative stay, intensive care unit (ICU) stay, mortality, and resumption of oral intake. Patients undergoing esophageal or pancreatic procedures sustained a significantly higher complication rate at most albumin levels, whereas colonic surgery resulted in lower complication rates at the same albumin levels. Resource use (eg, length of stay and ICU stay) related to these complication rates; esophageal and pancreatic procedures used the most resources and colon procedures used the fewest at most albumin levels. This lack of appreciation for nutritional risk and operative site can explain discrepancies in outcome noted in several randomized, prospective nutritional studies and must be applied to the design and implementation of new studies. Elective, non-emergent esophageal and pancreatic procedures performed in patients who could have had surgery delayed for preoperative nutrition, but did not, result in higher risk than colon surgery at any given level of serum albumin below 3.25 g/dL. Patient populations in trials should be stratified by operative site and by markers of nutritional status. Degree of hypoalbuminemia and other potential markers of nutritional status may explain many of the discrepancies between trials of nutrition support. Preexisting hypoalbuminemia in patients undergoing elective surgery remains underappreciated, unrecognized, and untreated in many hospitalized patients.

Role of Soluble Receptors for Tumor Necrosis Factor Alpha in the Development of Hypoalbuminemia in Hemodialysis Patients

Background: Hypoalbuminemia is a significant predictor of mortality in patients on hemodialysis (HD). The cause of hypoalbuminemia in HD patients, however, remains to be clarified. Recent studies have demonstrated that high blood concentrations of soluble receptors for tumor necrosis factor (sTNFRs) are associated with malnutrition in a variety of diseases and that the blood sTNFRs concentrations are elevated in HD patients. Methods: The serum concentrations of tumor necrosis factor alpha, sTNFR (p55 and p80), and interleukin (IL) 6 were measured in 21 HD patients with low (equal to or less than 3.6 g/dl) and in 19 HD patients with normal (equal to or more than 4.0 g/dl) concentrations of serum albumin who were free from acute infection, malignancy, collagen diseases, liver diseases, or surgery. The correlation between these parameters and the degree of hypoalbuminemia was examined. Results: The serum concentrations of sTNFR p80 and IL-6 were significantly higher in patients with hypoalbuminemia as compared with those with normoalbuminemia (sTNFR p80: 47.4 ± 4.7 vs. 35.3 ± 2.1 ng/ml, p < 0.05; IL-6: 10.8 ± 2.0 vs. 6.3 ± 0.5 pg/ml, p < 0.05). In contrast, there was no difference in the serum concentrations of tumor necrosis factor alpha and sTNFR p55 between the two groups. Multivariate regression analysis showed that sTNFR p80 but not IL-6 significantly influenced the serum albumin concentrations. There were no significant differences in body mass index, serum total cholesterol, and normalized protein catabolic rate between the two groups. Conclusions: Our results suggest the development of hypoalbuminemia in some HD patients who do not have any obvious cause of hypoalbuminemia and that high concentrations of sTNFR p80 might contribute to the development of hypoalbuminemia in patients on long-term HD.

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute- phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF- alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis. (Am J Kidney Dis 1998 Jul;32(1):107-14)

Urine kallikrein excretion in relation to renal sodium handling in minimal change nephrotic syndrome

Twenty-four-hour urine kallikrein excretion (Uka), urine protein excretion, renal sodium handling, and the activity of the renin-angiotensin-aldosterone system were serially studied in 11 children at three different stages of the minimal change nephrotic syndrome (MCNS)-edema forming state, proteinuric steady state in which a relapse of the disease was just starting but no edema as yet and remission. The value for Uka was significantly increased in the edema forming state in contrast to the normal values of proteinuric steady state and remission. Serum sodium concentration was only decreased in the edema forming state and the degree of hypoalbuminemia and proteinuria did not differ between the edema forming and proteinuric steady states. Urine volume, absolute and fractional sodium excretion were significantly decreased in the edema forming and proteinuric steady states as compared with those in remission, suggesting that sodium retention was present in both states of the disease although the change in these parameters was more profound in the edema forming state than in the proteinuric steady state. Creatinine clearance did not differ among each stage of the disease. Plasma renin activity and plasma aldosterone concentration were significantly increased in the edema forming state as compared with those in the proteinuric steady state and remission. Plasma renin activity and plasma aldosterone concentration were significantly correlated directly with Uka and plasma aldosterone concentration was correlated inversely with urine sodium excretion. No relation was noted between Uka and other variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of prednisolone in children with nephrosis.

The pharmacokinetics of prednisolone given intravenously were studied in 11 children with relapsed steroid responsive nephrotic syndrome, and four control subjects. The clearance of both total and unbound drug was decreased in these children and the unbound fraction of the drug in plasma was significantly correlated with the degree of hypoalbuminaemia. We conclude that changes in the clearance of prednisolone and altered protein binding might account for some of the variability in both therapeutic responses and the incidence of toxicity in patients treated with standard dosage regimens.

Transport proteins as indices of protein status

The terms protein status and protein deficiency have been used to denote several quite different concepts. Before beginning to consider how best to measure protein status, and the place of transport protein concentration in this measurement, we must be precise about what we are trying to measure. Laboratory animal investigators clearly refer to the condition resulting from an insufficiency of protein in the diet when they use these terms, irrespective of the clinical or biochemical findings that these diets produce. Clinicians on the other hand refer to a variety of clinical or biochemical findings in the patient, irrespective of the antecedent diet. Thus protein deficiency has been used synonymously with kwashiorkor, nutritional edema, and also for reduced levels of the transport proteins-albumin, transferrin (1), retinolbinding protein, and prealbumin (2). Field workers use the terms in a totally different way-to indicate a lack of body protein in the body compositional sense. It is clear that the very concept of protein deficiency enshrines a whole chain of events. Any particular investigator tacitly assumes the whole chain to exist if he observes a single link in the chain. In essence the thesis is that a protein-deficient diet leads to a loss of body protein, the loss being identified as due to protein deficiency, and not energy deficiency or some other condition, though a coincident reduction in the circulating transport proteins. This in turn leads to edema, skin sores, fatty liver, and the other features of “pure” kwashiorkor. Developing a body protein deficit is synonymous with being in negative nitrogen balance. Consideration of the numerous causes of a negative nitrogen balance indicates the totally nonspecific nature of a protein deficit with respect to various dietary components, trauma and disease. There is no constant relationship between any transport protein and the total amount of protein in the body relative to an appropriate standard; it is only when a body protein deficit arising from a specific cause is considered that a relationship is to be expected. Transport proteins have assumed a special place in the chain of events because they are thought to identify whether a body protein deficit is due to a dietary protein deficiency or not. Because of this the level of circulating transport protein, traditionally albumin, has been used to define protein deficiency in clinical practice; indeed many people hold the view that the degree of hypoalbuminaemia indicates the relative importance of a dietary protein deficiency with respect to energy, or other deficiency, in a malnourished individual. Because of the relatively long half-life of albumin, other transport proteins that respond more rapidly to alterations in the diet have been suggested as more sensitive indices of the degree of dietary protein deficiency (1, 2). For those who define protein status on the basis of the levels of these transport proteins an appraisal of their use in the evaluation of protein status is impossible: this immediately leads to a circular and self-fulfilling argument. Without an independent and true estimate it is not possible to evaluate the reliability with which any particular measurement reflects protein status. The independent measurement of protein status has to be an accurate measurement of protein intake, relative to an estimate of protein requirement, that has itself been derived without recourse to transport protein measurement. In order for a transport protein measurement to be a useful measurement of protein status it is not sufficient for it to respond precisely when a protein-deficient diet is

Effects of level of larval intake on the productivity and physiological and metabolic responses of lambs infected with Trichostrongylus colubriformis

The interrelationships between level of exposure to Trichostrongylus colubriformis infection, production loss, and the physiological and metabolic changes associated with the development of the disease were studied over 24 weeks in groups of weaner lambs on larval dosing regimes (LDR) of either 0, 300, 950, 3000, 9500 or 30,000 infective larvae per week. During the first 12 weeks faecal egg counts generally accorded with the level of larval dosing, but thereafter declined, and at 24 weeks worm counts showed that most animals were resistant to parasite establishment. Liveweight gain over the 24-week infection period was significantly depressed only on LDR 3000, 9500 and 30,000 being, respectively, 67, 61 and 49% of the gain on LDR 0. These differences reflected reduced rates of gain, or, on LDR 30,000, loss of weight, during the first 12 weeks; rates of liveweight gain were similar on all LDR between 12 and 24 weeks. Wool growth rate was significantly depressed on LDR 3000, 9500 and 30,000, the maximal effect being recorded during weeks 8-12, when the growth rate was reduced to 79, 47 and 44% respectively of the rate on LDR 0. Thereafter, wool growth rate on these three LDR increased and by weeks 20-24 had returned almost to the level in uninfected sheep. Food consumption was significantly depressed on LDR 3000, 9500 and 30,000, the maximal effect occurring between weeks 8 and 12 when food consumption was 71, 61 and 44% respectively of that on LDR 0. By weeks 20-24 food consumption on these LDR had returned to the level in uninfected sheep. On LDR 30,000 there was a significantly increased excretion of nitrogen (g/100 g nitrogen intake) in faeces during the 8th, 12th and 24th weeks of infection and in urine during the 4th, 8th and 12th weeks. Nitrogen retention (g/100 g nitrogen apparently digested) was significantly reduced on LDR 30,000 during the 4th, 8th and 12th weeks. Enteric loss of plasma was significantly increased on LDR 950 and above, this effect occurring earlier and being more pronounced with increasing level of larval dosing; maximal losses were recorded during the 12th week when on LDR 30,000 sheep were losing approximately four times as much plasma into the gut as on LDR 0. The development and degree of hypoalbuminaemia in infected sheep paralleled the development of enteric plasma leakage, significantly reduced albumin levels being recorded on LDR 950 and above during the 12th week. By the 24th week both enteric plasma loss and plasma albumin concentration in sheep on these four LDR had returned to values similar to those in uninfected sheep. Measurements of albumin kinetics indicated that rates of albumin turnover and irreversible loss were increased in infected sheep only during the early stages of infection. Depletion of the albumin pool was accompanied by a significantly reduced rate of irreversible albumin loss during the 12th week on LDR 3000 and above. Measurements of the RNA/DNA ratio in liver and muscle at 4, 10 and 17 weeks indicated that protein synthesis in these tissues was significantly depressed only on LDR 30,000. Catabolism of muscle protein declined concomitantly with reduced food consumption.

Lipids and Lipoproteins in Chronic Uraemia. A Study of the Influence of Regular Haemodialysis**

Plasma lipids and lipoproteins were studied in a group of chronic uraemia patients some of whom were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patient. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.

Binding of 14-C-salicylic acid and 14-C-pentobarbital to plasma proteins of several species during the perinatal period.

The fraction binding of 14-C-salicylic acid and 14-C-pentobarbital was studied as a function of age in plasma of the pig, dog, goat and human. The pig exhibited an unusual degree of hypoalbuminemia and low fractional binding of salicylic acid at birth. Albumin levels and the percent binding of the salicylic acid were not significantly lower in newborn plasma than in adult plasma of the other species studied. The pig was also exceptional in that the high fractional binding of pentobarbital observed at low ligand concentrations in plasma of the newborn was not observed in the other species studied. Depletion of albumin in newborn pig plasma did not appreciably affect the binding of pentobarbital. Thus it is suggested that the plasma of the fetal and newborn pig may contain a nonalbuminoid protein, such as fetal globulin, which is capable of binding pentobarbital but does not have a high avidity for salicylic acid. It apparently does not exist at birth in the plasmas of the other species studied, as depletion of albumin markedly reduced the fractional binding of pentobarbital.

Electrophoretic Changes in Plasma Proteins in Patients with Pneumococcic Infections

SummaryMultiple electrophoretic determinations of the plasma proteins of 23 patients with pneumococcic pneumonia or meningitis have been made in relation to the duration of the infection and the importance of antecedent factors. Hypoproteinemia, due largely to significant progressive hypoalbuminemia, together with early increases in alpha-globulins and fibrinogen have been observed. Malnutrition, chronic alcoholism, cirrhosis and chronic passive congestion of the liver were found associated with more severe degrees of hypoalbuminemia. Diminished plasma albumin levels were seldom restored to normal within a month from the onset of the infection. The effects of intramuscular injections of immune human gamma globulin were investigated, with inconclusive results.

EXPERIMENTAL HYPOALBUMINEMIA

1. Adult dogs maintained for 6 weeks upon a carrot-protein-deficient diet exhibited a progressive fall in the serum protein confined entirely to the albumin fraction. The degree of hypoalbuminemia was pronounced, i.e. a fall from 3.75 to 2.00 gm. per cent. 2. Parallel microscopic changes in the liver were observed which consisted of a gradual loss in the stainable cytoplasm producing extensive vacuolization. This vacuolization was not due to the accumulation of fat or of glycogen as shown by chemical analyses as well as by stained sections of the livers. 3. The histological changes in the livers were assumed to be due to a loss of protein inasmuch as there was a parallel fall in the protein content of the liver pari passu with the fall in the serum albumin of the blood. This assumption is made more probable by the fact that the water content of the liver increased as the protein content decreased. 4. Liver function, as measured by the excretion of iso-iodeikon, fell with the fall of the serum albumin thus indicating the production of hepatic insufficiency by the protein deficient diet. 5. These observations are discussed in relation to the question whether the liver is the site of formation or of storage of serum albumin. Certain other, particularly therapeutic, implications are also discussed, i.e. the importance of a high protein intake in patients with liver disease.