Fall In Serum Albumin Research Articles

Study of Serum Albumin as a Prognostic Marker in Critically ILL Patients

ntroduction: Serum albumin is an important parameter in the assessment of the nutritional status of both acute and chronically ill patients(1), Low albumin levels have been associated with morbidity and mortality in critically ill patients. It is thus, important to identify the patients at the time of admission who are likely to have a poor outcome, so that such patients can be managed aggressively.AIM: Study Of Serum Albumin As a Prognostic Marker in Critically ill patients.Materials and Methods: After approval from the Institutional Ethical committee all patients were selected as per inclusion and exclusion criteria. The patients, who are critically ill was selected from MICU and Serum albumin level was measured by BECKMAN COULTER ANALYZER. The statistical analysis was performed by statistical software SPSS version 21.0.Result: The present cross- sectional study was conducted in the department of medicine, among 100 critically ill Patients The results show that there is a steady fall in serum albumin in both groups. However, the fall in nonsurvivors was more steep than survivors. When mean albumin was compared statistically at different intervals, it was found to be statistically significant.Conclusion: Serum albumin is a cheap and cost effective and is routinely measured in all critically ill patients. Thus serum albumin serves as a powerful prognostic tool for critically ill patients.

To find the role of postoperative fall in serum albumin as a predictor of outcome after major abdominal surgery

To find the role of postoperative fall in serum albumin as a predictor of outcome after major abdominal surgery

A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study

Background: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had ­diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7; kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. Conclusions: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. Trial Registration: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.

Combating protein energy wasting in end stage kidney disease: role of exogenous proteolytic enzyme as an adjuvant to dietary protein

Background: Despite interventions, the prevalence of protein energy wasting in patients on dialysis continues to be unacceptably high. The objective of the study is to evaluate the efficacy of exogenous proteolytic enzyme, as an adjuvant to dietary protein in improving the nutritional status.Methods: This is a retrospective, real world, single centre, observational study, aimed at assessing the changes in key nutritional indices, over 6 months in patients with chronic kidney disease (CKD) initiated on continuous ambulatory peritoneal dialysis (CAPD). The intervention included addition of egg protein and use of an exogenous proteolytic enzyme. Three cohorts were identified. Cohort 1, had access to a nephrologist and CAPD counsellor; Cohort 2, in addition had access to a dietician who emphasized the need for increase in dietary protein in form of 4-6 eggs a day; and cohort 3, were in addition given an exogenous proteolytic enzyme with the major protein meal.Results: The absolute fall in serum albumin at 6 months for the cohort 1, 2 and 3 is 0.48, 0.29 and 0.09 gm/dl respectively. Not only was the fall in serum albumin significantly less with the use of exogenous proteolytic enzyme, a higher proportion of patients were able to maintain or improve their serum albumin. The fall in midarm circumference was maximum in cohort 1 (2.08 cm) and least in cohort 3 (0.45 cm). This positive trend however, did not achieve statistical significance.Conclusions: Use of exogenous proteolytic enzyme, when combined with egg protein, improves key nutritional indices in patients of CKD on CAPD.

Consumption of Green Tea ( Camellia sinensis ) Improves Lipid, Hepatic, and Hematological Profiles of Rats That Are Submitted to Long-Term Androgenic Stimulation

Indiscriminate use of anabolic steroids is associated with cardiovascular diseases, such as myocardial infarction, thrombosis, and arterial obstruction. Furthermore, high levels of androgens increase hepatic toxicity and the risk of cancer. Contrastingly, green tea prevents and controls cardiovascular and hepatic diseases, as it can improve the lipid profile and reduce inflammation and effects of oxidative stress. This study will evaluate benefits of green tea consumption, to attenuate systemic damage caused by supraphysiological doses of testosterone, by analyzing the lipid, biochemical, and hematological profiles of 28 42-day-old male Wistar rats. Silicone pellets containing testosterone in proportion were surgically implanted and replaced in these rats every four weeks, and they received casein-based control feed and water or green tea for hydration. After 20 weeks, all the male rats were anesthetized and their blood samples collected for the analysis of their biochemical and hematological profiles. Although the high hormone concentration had a negative influence on the lipid profile of these animals, the groups that consumed green tea exhibited a reduction in serum triglycerides (62%), Low Density Lipoprotein (76%), and Very Low Density Lipoprotein (45%). Tea consumption also led to a significant reduction in total cholesterol (32% in the green tea control group and 45% in the green tea-induced group), without changing the High Density Lipoprotein fraction. Only the green tea-induced group manifested a reduction in the total concentration of serum proteins. A fall in serum albumin was observed in the green tea-induced groups (2.3 g/dL) compared to control groups (2.9 g/dL). The induced group presented elevation in hematocrit, erythrocytosis, and leukocytosis in contrast to the green tea-induced group. The green tea control group maintained erythrocytosis, but without any other potentially harmful effect. A 30% increase in lymphocyte population in the induced group was observed. There was no difference in the platelet count of these rodents. Hepatic enzymes were also shown to have increased in the induced group, indicating hepatic injury in this group due to exposure to testosterone. This effect was reversed in the tea groups. From this, its possible to reach the conclusion that consumption of green tea shields the lipid profile, proteins, liver enzymes and hematological profile, thus reducing risk factors related to the supraphysiological doses of testosterone.

Change in Physiological Variables in the Last Two Weeks of Life: An Observational Study of Hospitalized Adults With Heart Failure

ContextRecognition of dying is a difficult task in end-stage heart failure, yet it remains an important clinical skill in providing good palliative care to these patients. ObjectivesTo use routinely collected data to explore evidence for physiological change in the final two weeks of life in end-stage heart failure. MethodsThis was a retrospective cohort study of routinely collected data from hospital inpatients dying as a result of heart failure during a one-year period in a U.K. hospital. Data were analyzed using descriptive techniques and multilevel modeling. ResultsResults were obtained on 81 patients. Respiratory function (evidenced by falling oxygen saturation and rising respiratory rate) deteriorated by a clinically significant amount in the final two weeks of life (P < 0.001). Renal function (evidenced by rising serum urea and creatinine) also demonstrated a clinically significant deterioration over the same period (P < 0.001 and P = 0.005, respectively). Serum albumin fell over a period of months (P < 0.001). Heart rate and blood pressure did not demonstrate clinically significant change over the same period. ConclusionsDeteriorating respiratory and renal function may indicate imminent dying in heart failure. A fall in serum albumin may signify poor prognosis over a timescale of weeks to months. Conversely, hemodynamic parameters may remain relatively stable in the final days of life and should not be reassuring in end-stage heart failure patients.

010 Multicentre validation of the adverse prognostic implications of declining serum albumin levels in chronic heart failure

Background Single-centre studies have shown that a low serum albumin at baseline forecasts enhanced mortality in chronic heart failure (CHF) possibly because it reflects aberrations (eg, inflammation, impaired nutrition, plasma volume expansion) that can exacerbate disease. We hypothesised that attenuations in serum albumin over time would be prognostically more ominous than baseline values, and would be so even in a multicentre setting. Methods We analysed the survival implications of baseline albumin and ∆albumin in a derivation cohort of 246 CHF outpatients (mean [±SD] age 68±12 years, LVEF 29±8%, 48% NYHA class >2) from University College London Hospital and then in a validation cohort of 148 CHF outpatients (age 69±12 years, LVEF 28±10%, 41% NYHA class >2) from Imperial Healthcare (St Marys Hospital and Hammersmith Hospital, London). Results In the derivation cohort, 51 (21%) patients died over 13 months. Baseline albumin independently predicted mortality (HR 0.89, 95% CI 0.84 to 0.94, χ 2 :18, p 2 :53, p 6 g/l optimally predicted death (ROC AUC 0.82, p 2 value (43 vs 84, p 2 : 44, p 6 g/l predicting an ∼sixfold increased risk (HR 5.64, 95% CI 3.08 to 10.31, χ 2 : 35, p 2 value (51 vs 65, p Conclusions A fall in serum albumin over time consistently predicts an amplified risk of death in systolic CHF and enables simple and cheap risk stratification.

Prospective longitudinal study of biochemical changes in critically ill patients with severe traumatic brain injury: Factors associated and outcome at 6 months

Biochemical prognostic markers of severe traumatic brain injury have not been clearly identified. This study was conducted to study biochemical changes in patients with severe traumatic brain injury, with respect to neurological outcome.Adult patients admitted within 24 hours of traumatic brain injury with Glasgow Coma Score 4-8, were prospectively studied for changes in various biochemical parameters. Outcome was assessed at 6 months. The mean serum albumin levels showed progressive fall till 2 weeks from 3.23 g/dL to nadir value of 2.86 g/dL, followed by mild increase to 2.99 g/dL at 3 weeks (p<0.001). The mean daily urine creatinine values demonstrated significant fall from 1255.4 mg/d to 1010.2 mg/d at 3 weeks (p<0.001). There was significant increase in mortality at 2 months among patients with atleast 15% fall in serum albumin and urine creatinine less than 1000 mg/d at 3 weeks (p < 0.005). Unfavorable outcome was noted in 12 out of 15, with at least 15% fall in serum albumin at 3 weeks, compared to 11 out of 25, with less than 15% fall in serum albumin (p=0.03). Unfavorable outcome was also noted in 16 out of 22, with low urine creatinine (<1000 mg/d) at 3 weeks, compared to 6 out of 17, with normal urine creatinine (p=0.02).In patients with severe TBI, unfavorable neurological outcome at 6 months was associated with 15% fall of serum albumin or low urinary creatinine at 3 weeks, more so with the former.

Acquired intestinal lymphangiectasia successfully treated with a low-fat and medium-chain triacylglycerol-enriched diet in a patient with liver transplantation

Intestinal lymphangiectasia is defined as a dilatation of small bowel lymphatic capillaries and a loss of lymph into the bowel lumen. Clinically it is characterized by hypoproteinaemia and oedema. We present here a case of protein-losing enteropathy due to intestinal lymphangiectasia after liver transplantation in a 57-year-old man who was transplanted for hepatitis C virus. Four years after liver transplantation, the patient developed hypoalbuminaemia and ascites associated with recurrence of cirrhosis. The sudden fall in serum albumin led us to look for a cause of reduction other than or in addition to cirrhosis. Duodenal biopsies showed tall villi with dilated lymphatic vessels and widening of the villi caused by oedema, demonstrating intestinal lymphangiectasia. In this case a low-fat diet supplemented with medium-chain triacylglycerols achieved an early clinical improvement with increased serum albumin levels and ascites disappearance. Intestinal lymphangiectasia should be suspected in liver-transplanted patients developing hypoproteinaemia and hypoalbuminaemia after the recurrence of cirrhosis.

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Hypoalbuminemia is a poor predictor of survival after percutaneous endoscopic gastrostomy in elderly patients with dementia

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is widely used for long-term enteral nutrition in patients with dementia and inadequate oral intake, although its benefit in prolonging the survival of the patient is not clear. Patients are often referred for PEG placement after a significant weight loss or fall in serum albumin. It is not known whether this delay in referral adversely affects the survival. Our aim was to determine the survival after PEG placement in patients with inadequate oral intake secondary to cognitive impairment and to determine whether the nutritional parameters at the time of placement of PEG predict survival. METHODS: After excluding patients with cancer, cerebrovascular accident (CVA), and anoxic encephalopathy, 56 consecutive patients with dementia and inadequate oral intake were included in the study. The following parameters were analyzed to predict survival benefit: demographics, reason for admission to the hospital, nutritional indices, Karnofsky performance status before and after PEG, comorbid medical illnesses, and complications after PEG. A control group was selected from patients admitted to the geriatric division who did not receive PEG. Patients with CVA, cancer, and anoxic encephalopathy were also excluded in the control group. Both groups were followed-up for 6 months. RESULTS: One patient was lost to follow-up and complete data were available for 55 patients. The control group of 33 patients was comparable to the patients in age, gender, and comorbid illnesses. During a 6-month follow-up period, the mortality was 44% among patients and 26% among controls ( p = 0.03). The only factor that predicted poor survival in patients at 6 months was a serum albumin of <2.8 g/dl. The predictive value of low serum albumin was higher in patients with sepsis on hospital admission and in patients younger than 85 yr. The mean serum albumin of the patients was significantly lower than the control group ( p = 0.0001). CONCLUSIONS: Only 50% of demented patients with inadequate oral intake are likely to survive beyond 6 months after PEG placement. No improvement in performance status is likely to occur in any patient. These limited benefits should be realized before initiating PEG feeding. Since the survival in the age-matched control group with a higher mean serum albumin was better than in the patients who had PEG, there may be some benefit in performing PEG before the onset of severe hypoalbuminemia.

Hypoalbuminemia is a poor predictor of survival after percutaneous endoscopic gastrostomy in elderly patients with dementia

Percutaneous endoscopic gastrostomy (PEG) is widely used for long-term enteral nutrition in patients with dementia and inadequate oral intake, although its benefit in prolonging the survival of the patient is not clear. Patients are often referred for PEG placement after a significant weight loss or fall in serum albumin. It is not known whether this delay in referral adversely affects the survival. Our aim was to determine the survival after PEG placement in patients with inadequate oral intake secondary to cognitive impairment and to determine whether-the nutritional parameters at the time of placement of PEG predict survival. After excluding patients with cancer, cerebrovascular accident (CVA), and anoxic encephalopathy, 56 consecutive patients with dementia and inadequate oral intake were included in the study. The following parameters were analyzed to predict survival benefit: demographics, reason for admission to the hospital, nutritional indices, Karnofsky performance status before and after PEG, comorbid medical illnesses, and complications after PEG. A control group was selected from patients admitted to the geriatric division who did not receive PEG. Patients with CVA, cancer, and anoxic encephalopathy were also excluded in the control group. Both groups were followed-up for 6 months. One patient was lost to follow-up and complete data were available for 55 patients. The control group of 33 patients was comparable to the patients in age, gender, and comorbid illnesses. During a 6-month follow-up period, the mortality was 44% among patients and 26% among controls (p = 0.03). The only factor that predicted poor survival in patients at 6 months was a serum albumin of <2.8 g/dl. The predictive value of low serum albumin was higher in patients with sepsis on hospital admission and in patients younger than 85 yr. The mean serum albumin of the patients was significantly lower than the control group (p = 0.0001). Only 50% of demented patients with inadequate oral intake are likely to survive beyond 6 months after PEG placement. No improvement in performance status is likely to occur in any patient. These limited benefits should be realized before initiating PEG feeding. Since the survival in the age-matched control group with a higher mean serum albumin was better than in the patients who had PEG, there may be some benefit in performing PEG before the onset of severe hypoalbuminemia.

In vivo microvascular clearance of albumin in renal and extrarenal tissues in puromycin aminonucleoside (PAN) induced nephrotic syndrome.

The nephrotic syndrome is characterized by generalized oedema considered to be due to the fall in serum albumin and to sodium retention. The aim of the present study was to investigate whether a generalized disturbance in vascular integrity contributes to the oedema formation. We used the PAN-(puromycin aminonucleoside) nephritis model in order to induce the nephrotic syndrome in female Wistar rats. Eight rats were given PAN, 15 mg/100 g body weight, intraperitoneally 10 days prior to the study, whereas 21 rats served as controls. Albumin clearance to tissues was measured using a dual isotope technique. Repeated blood samples as well as samples from various muscles, kidney, liver, lung, heart, abdominal wall and from ascites fluid were taken to determine radioactivity and tissue dry-to-wet weights. Clearance of albumin (Clalb) from plasma to interstitium was calculated from the (linear) increment in 'plasma equivalent tissue albumin space' as a function of time, corrected for intravascular volume and oedema. The plasma and urine concentrations of albumin were determined in a parallel study by single radial diffusion using monospecific rabbit anti-rat antiserum in seven PAN animals and 13 controls. A marked fall in dry-to-wet weight ratios together with pronounced proteinuria, oedema and ascites were found in the PAN animals. Haematocrit decreased from 45% (32-51) to 30% (28-38) and serum albumin from 22.0 g/l (16.3-25.2) to 4.94 g/l (3.20-6.72) in control and PAN animals, respectively. However, Clalb apparently remained unchanged in the PAN animals in comparison to controls in most tissues examined. Thus, in these in vivo experiments there was no direct evidence of an increased extravasation of albumin in extrarenal tissues. There was no strong support for the contention that a generalized disturbance of capillary integrity outside the renal vasculature would contribute to the oedema formation in the PAN nephrotic syndrome.

ENTERAL FEEDING FOR CHILDREN UNDERGOING BONE MARROW TRANSPLANTATION

21 Children undergoing bone marrow transplantation (BMT) usually need nutritional support (NS) during their treatment. Because of frequent vomiting they mostly receive total parenteral nutrition (TPN). Enteral nutrition (EN) has been little studied in this group of children [1]. Objective: To evaluate the use of EN in children undergoing BMT Design: Prospective, clinical trial. Patients and methods: From September 1996 until December 1997 all 37 children admitted for BMT were invited to participate and informed consent was asked to their parents. Thirty-four children (mean age 8 years) entered the study and were allocated to group A (EN; n=12) or B (TPN; n=22). The haematological and non-haematological disorders for which BMT was indicated, were similarly distributed in both groups. NS started when the oral intake was <75% of the requirements. If EN was consistently not tolerated (vomiting), TPN was given. Energy, protein and fluid requirements were calculated according to the Schofield formula, the Dutch Recommended Dietary Allowances and the ASPEN-formula, respectively. The nutritional status was assessed at admission and at days 30 and 90 after BMT, using anthropometric measurements (expressed as SDS) and serum albumin. The frequency of vomiting, diarrhea, sepsis and cholestasis was registered. Results: NS was necessary in 82% of the 880 hospitalization days in group A and in 60% of the 1732 hospitalization days in group B. EN was possible during 42% of the NS days (303 days, group A). Three children received exclusively EN. The mean nutritional intake per day was similar in groups A and B and reached more than 85% of the requirements. The anthropometric measurements, both in group A and B, were adequate at admission and remained adequate during hospitalisation. At admission, antropometry was similar in both groups, except for a significantly lower weight for height in A (p<0.05). During hospitalization, significant lower subscapular skinfold (day 30) and midupperarm-circumference, biceps-triceps skinfolds and weight for height (day 90) were found in group A, compared to group B. In group A the length-SDS was significantly lower at day 90 than at admission. A significant fall in serum albumin (p<0.05) was found on day 30 in both groups, but normalised at day 90. Vomiting occurred in 14.2% of the NS days in A (19.2% EN days) and in 20.6% of the NS days in B. Diarrhea was present in 34.0% of the NS days in A (27.7% EN days) vs. 27.5% NS days in B. In group A 12 episodes of sepsis developed in 8 children vs. 13 episodes in 11 children in B. Cholestasis was found in 3 children in A vs. 12 children in B. Acute Graft-versus-host-disease (GVHD) was not found in group A but in 6 children in group B. Conclusions: EN is possible in 42% of the NS days in children undergoing BMT and is associated with a lower frequency of cholestasis and GVHD and with a similar frequency of vomiting and diarrhea than TPN. The significant decrease in serum albumin found at day 30, suggests that children undergoing BMT have a higher protein requirement than calculated using standard methods.

Albumin kinetics in hypoalbuminemic patients receiving total parenteral nutrition.

By using undenatured purified albumin preparations radiolabeled with iodine, the half-life of serum albumin in well patients who are stable is known to be approximately 17 days. However, when a patient is suffering with an acute illness such as sepsis, trauma, burns or after an extensive operative procedure, the serum albumin level decreases. It is not known whether this fall in serum albumin is due to increased catabolism, decreased synthesis, or a combination of both factors. This study explores the kinetics of albumin catabolism under these circumstances to clarify the issue. 125I-labeled albumin was administered intravenously to 10 critically ill, hypoalbuminemic patients receiving total parenteral nutrition (TPN). Each subject had frequent blood samples taken for at least 10 days to measure the decline of plasma radioactivity over time. None was receiving unlabeled albumin during the investigation. It was assumed that the plasma decay would follow first-order kinetics after the early equilibration phase. Radioactivity of heparinized blood samples (counts/2 mL sample) were counted and the results were graphically expressed. One subject was not evaluated because he was discharged on the 8th day. The APACHE (acute physiology and chronic health evaluation) score for the other nine subjects ranged from 4 to 18 (mean, 7.5). The serum albumin remained below 3.0 g/dL in each subject and did not change statistically throughout the study. The radioiodinated albumin half-life ranged from 5.52 to 11.76 days (mean 9.10 days; compared with published normal of approximately 17 days). The equilibration time was 3 to 7 days. The average albumin catabolized for this group is similar to previously reported normal subjects, 0.18 g/kg/d. Hypoalbuminemic patients receiving TPN have markedly shortened plasma albumin half-lives, but the albumin catabolized per day is similar to normal patients. These data argue for both a synthetic and catabolic defect that explains the hypoalbuminemia in this patient group.

Gastrointestinal and nutritional sequelae of bone marrow transplantation.

The nature of the gastrointestinal injury following bone marrow transplantation and its clinical and nutritional sequelae are poorly defined. Prospective assessments of gastrointestinal function, nutritional status, and wellbeing were therefore carried out in 47 consecutive patients (28 males, 19 females; mean age 8.4 years) undergoing bone marrow transplant. 31 diarrhoeal episodes (median duration 9.5 days) occurred in 27 patients at a median of 10 days after transplantation. Ninety one per cent of episodes were associated with protein losing enteropathy. Protein losing enteropathy was more severe in graft-versus-host disease (GVHD) comparing with other causes. It led to a substantial fall in serum albumin and there was a negative correlation between faecal alpha 1-antitrypsin concentrations and serum albumin. Transient pancreatic insufficiency developed in 18 patients, and pancreatitis in one. Intestinal permeability was normal in 12 patients who had no diarrhoea during the conditioning treatments. Diarrhoeal patients had a significantly greater decrease in nutritional status and wellbeing than patients without diarrhoea. Gastrointestinal injury following bone marrow transplantation is thus complex. Severe protein losing enteropathy in this context suggests the presence of GVHD.

Liver Regeneration in Children after Major Hepatectomy for Malignancy—Evaluation Using a Computer-Aided Technique of Volume Measurement

Purpose: The time course of hepatic volume regeneration and return of excretory and synthetic function was studied in eight children undergoing lobar or extended lobar liver resections for hepatoblastoma (n= 5), hepatoma (n= 1), and recurrent nephroblastoma (n= 2). Five patients received preoperative and all were administered postoperative chemotherapy. Whole-liver irradiation was administered to one patient. One additional patient who underwent an extended hepatic resection for benign disease and did not receive chemotherapy was included for comparison. Methods: A previously validated technique of computer-aided volume measurement was used to measure liver volumes from serial CT scans obtained after hepatic surgery. Normal liver volume as a function of age was determined from the literature and the time course of regeneration was compared to normal liver growth. Postoperative serum albumin, total bilirubin, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were recorded and correlated with volume regeneration. Results: In six patients hepatic regeneration had progressed to normal volume by 90 days after resection (normal volume for age was achieved by 50 days in three patients). There was an initial rapid rate of regeneration (>10 cc/day) which declined to a normal rate of less than 0.5 cc/day at 90 days after surgery. Two children with failure to thrive displayed the same pattern of rapid regeneration, attaining a volume appropriate for weight but less than that expected for age. The shape of the liver volume regeneration curve was similar in one additional patient undergoing an extended left lobectomy for benign disease. A brief rise in bilirubin occurred during the first week and a transient fall in serum albumin was followed by resumption of normal synthetic capacity within 6 weeks in all but two patients. Conclusions: Liver regeneration in children is a rapid process occurring despite the administration of cytotoxic agents and hepatic irradiation.

Diarrhea and weight loss after bone marrow transplantation in children.

To define the determinants of diarrhea after bone marrow transplantation (BMT) and its nutritional sequelae, the medical records of 20 consecutive children (median age, 9 years; 13 boys and 7 girls) undergoing BMT at Children's Hospital in Birmingham, UK were surveyed. All patients who received total body irradiation (TBI) required parenteral nutrition (PN). Seventy-eight percent of TBI patients and 73% of children who received allografts developed diarrhea compared with only 27% of non-TBI patients and 22% of those who received autografts (P < 0.05). Ninety percent of children with diarrhea required PN. Duration of PN in these children was longer than in those without diarrhea who requested PN (P < 0.05). Despite PN, weight loss at discharge was still greater in the study group (P < 0.05). Diarrhea was associated with a significant fall in serum albumin (P < 0.005). Diarrhea and weight loss occur in children after BMT despite active PN support. Pretransplant TBI and the use of allografts are important determinants of these complications.

The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant Interleukin-2

The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 X 10(6) IU m-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 X 10(6) IU m-2 day-1). Toxicity, as judged by hypotension (P = less than 0.005) and capillary leakage (fall in serum albumin 18.2 vs 4.0 gm l-1; P = less than 0.0005 and weight gain 4.0 vs 1.2 kg; P = less than 0.025) were worse with the esc. dose protocol. PMN became activated following IL-2 with mean peak elastase/alpha 1-antitrypsin (E alpha 1 A) and lactoferrin values of 212 (SEM = 37) and 534 (SEM = 92) ng ml-1 respectively occurring 6 h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500 ng ml-1. Activation of the complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM = 0.6); esc. dose 25.7 (SEM = 6.33); P = less than 0.005) on day 5 of IL-2. There was a significant correlation between C3a levels and the degree of hypotention during the first 24 h after IL-2 (r = 0.91) and parameters of capillary leakage such as weight gain and fall in serum albumin (r = 0.71). These data suggest that activation of PMN initiates endothelial cell damage which subsequently leads to activation of the complement cascade. This latter system then contributes to the haemodynamic changes and capillary leakage seen in IL-2 treated patients.

Different responses of albumin-containing and alpha-fetoprotein-containing cells to estriol in the adult mouse liver.

A single intraperitoneal injection of 10 mg estriol (E3) rapidly induced a transient decrease in the serum albumin (ALB) level in 3 to 5 days in adult mice. At a dose of 5 mg, E3 showed a remarkable threshold effect on the decline of serum ALB. By immunohistochemistry, two types of ALB-positive cells were found in the liver. Type 1 cells were stained intensely and almost homogeneously throughout all or nearly all their entire cytoplasm, and type 2 cells showed only granular or vesicular cytoplasmic deposits. After administration of 10 mg E3, the type 1 cells diminished rapidly and markedly in direct proportion to the fall in serum ALB from the centro- and mediolobular zones, where they had been normally localized either singly or in small groups. Simultaneously, the granular or vesicular deposits that had been normally stained very weakly in the type 2 cells in the centro- and mediolobular zones became intensely stained along with cells in the perilobular zone. Alpha-fetoprotein (AFP)-containing cells in the liver appeared in maximal numbers at 5 to 7 days after E3 administration. These serological and cytological changes after E3 administration are here discussed on the basis of a possible inverse relationship between ALB and AFP gene expression.