Aluminium mobilization following renal transplantation and the possible effect on susceptibility to bacterial sepsis

We monitored urinary aluminium excretion in 60 renal allograft recipients for the first 6 months following transplantation. Plasma and urinary aluminium values steadily decreased during the study period. Patients who suffered two or more bacterial infections during this period excreted more urinary aluminium than those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpected increase in urinary aluminium excretion: 14 of these patients (60 per cent) had evidence of infection (10 bacterial and four viral), at this time. Both urinary aluminium and fractional aluminium excretion were greater in the 10 patients with bacterial infection than in the other 10 patients. Thus, patients who suffered bacterial infections had higher base-line urinary aluminium excretion, suggesting a higher body burden of aluminium. In addition, bacterial sepsis was associated with aluminium release from tissue stores with an associated increase in urinary aluminium excretion. This implies that patients with an increased body burden of aluminium are more prone to bacterial sepsis, and that aluminium excretion is increased during sepsis.     

Urinary tract infections beyond the early post-transplant period in pediatric renal graft recipients

BACKGROUND: Urinary tract infection is a frequent bacterial complication after renal transplantation in adults and children, however there are only very limited data on children beyond the early post-transplant period. In this study we investigated urinary tract infections in pediatric outpatients who had received transplants more than six months previously. Incidence, risk factors and impact on short-term graft function were analyzed. METHODS: 47 children who had received a total of 58 allografts were analyzed between 1997 and 2000. At the time of analysis they had had their transplants for an average of 3.5 years (range 0.5-9.4). Urinary tract infection was defined as the presence of both significant bacteriuria (> 10(5) CFU/ml) and symptoms. RESULTS: Of the 47 patients, 15 (32%) had from 1 to 7 urinary tract infections each. In total 35 infections were recorded. Median age at urinary tract infection was 5.5 years (range 1.8-24.2). Gender, donor source, immunosuppression and underlying disease (urologic vs non-urologic) did not influence the incidence of urinary tract infection. Creatinine but not C-reactive protein rose significantly during the infection. CONCLUSIONS: Our data suggest that urinary tract infection remains a frequent but mostly benign complication in the pediatric transplant population, even beyond the early post-transplant period. More extended studies are needed to assess the long-term effects on graft function.     

Imipenem/cilastatin as secondary therapy for bacterial infections

Imipenem/cilastatin (IPM/CS) was used to treat 39 documented infections in patients who had failed to respond to other antibiotic regimens. The overall response rating was 76.9%. Respiratory infections responded less frequently (efficacy rating, 55.6%) to IPM/CS than abdominal infections, urinary tract infections, or sepsis. Methicillin-resistant Staphylococcus aureus, Xanthomonas maltophilia, and Acinetobacter calcoaceticus were less sensitive to IPM/CS therapy than the other bacterial strains encountered. Respiratory tract infections were though to be less responsive to IPM/CS, probably because imipenem-resistant strains of S aureus were present in most of those cases. It is concluded that IPM/CS is well tolerated and effective in the treatment of various bacterial infections.     

Infection as a cause of early relapse in patients recovering from thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disorder characterized by hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic manifestations. Plasma exchange is the most effective treatment for this condition reducing mortality from 90% in untreated patients to 10%. However, infections acquired during the course of therapy could lead to early relapse of TTP. In this case report, we report three patients with TTP who initially responded well to plasma exchange treatments but suffered early relapses following bacterial infections. All these patients achieved remission once appropriate antibiotic therapy was instituted although one patient eventually received four courses of rituximab. This report emphasizes the need to be vigilant for new infections especially urinary tract infections in TTP patients undergoing plasma exchange. Instituting appropriate antibiotic therapy once an infection is suspected may reduce the need for prolonged plasma exchange procedures and extended hospital stay.     

Efficacy and safety of oral ciprofloxacin for treatment of serious urinary tract infections.

Eighty-three patients with serious urinary tract infections were treated with oral ciprofloxacin. Of these patients, 79 were hospitalized, and 41 had known structural or neurologic abnormalities of the urinary tract. The most common pathogens were members of the family Enterobacteriaceae (MICs, less than or equal to 0.06 microgram/ml), Pseudomonas aeruginosa (MICs, 0.13 to 2 micrograms/ml), and Enterococcus faecalis (MICs, 0.5 to 2 micrograms/ml). Sixty-eight patients were able to be evaluated for determining efficacy; all responded symptomatically, and all urinary pathogens were eradicated on days 3 to 5 of treatment. Five patients, who were treated for a relatively short duration (2 to 10 days), relapsed 5 to 9 days posttreatment. Six patients became colonized with yeasts during treatment, and seven patients developed bacterial reinfections 5 to 9 days posttreatment. All patients whose infections relapsed or who developed infections with new organisms had neurogenic bladders, structural abnormalities of the genitourinary tract, or urinary catheters. There was no instance of bacteria developing resistance during treatment. Ciprofloxacin probably caused nausea with or without vomiting in 7 of the 83 patients, headache in 3 patients, and mild elevation of hepatic enzymes in 2 patients; other adverse reactions were observed but were probably not drug related. Oral ciprofloxacin was effective and safe for the treatment of serious urinary tract infections caused by a variety of bacterial pathogens.     

Proteinuria in sickle cell trait and disease: an electrophoretic analysis

Using ultrafiltration and SDS-PAGE, abnormal urinary protein excretion was found in 25.4% of 189 persons with sickle cell disease and trait, but none of 72 controls. Based upon molecular weight of urinary proteins, underlying renal lesions were classified as glomerular, tubular, or both. Altered protein excretion appeared at an early age, was more abnormal in older subjects, and was related to the severity of sickle cell disease (SS greater than SC = S/beta Thal greater than AS). Since none of the subjects had yet developed clinically significant renal disease, SDS-PAGE may permit early detection of patients who require careful follow-up or aggressive therapy.     

Sex difference in the relationship of calcium and magnesium excretion to glycaemic control in type 1 diabetes mellitus.

In order to assess the variability and possible causes of calcium and magnesium losses in diabetes mellitus, urinary calcium and magnesium excretion were monitored six monthly over a 3-year period in 108 stable, type 1 diabetic patients who were having assessment of their clinical status and glycaemic control over the same period. In the patients studied the ranges of excretion of both calcium and magnesium were considerably wider than our non-diabetic reference ranges but the within subject variation in excretion was high. However, using mean values obtained over the study period, a direct relationship was observed between the excretion of both calcium and magnesium and HbA1 in female patients (P < 0.01) but not in males who had similar HbA1 values. The urinary excretion of calcium and magnesium did not relate to any of the other clinical or biochemical indices measured, including body mass index, daily insulin dose, retinal status or albumin excretion. It is suggested that, in poorly controlled patients, females may have a greater risk than males of developing the complications associated with chronic calcium and magnesium loss.     

Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG

BACKGROUND: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (alpha(1)-acid glycoprotein), albumin, alpha(1)-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. METHODS: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. RESULTS: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for alpha(1)-microglobulin, 33-fold for albumin, and 26-fold for IgG. CONCLUSIONS: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.     

Iron overload, but not treatment with desferrioxamine favours the development of septicemia in patients on maintenance hemodialysis

During a 19-month period we determined the incidence of bacterial infection among 39 patients treated with desferrioxamine who had end-stage renal disease and were undergoing maintenance hemodialysis. Twenty-three received desferrioxamine because of aluminum-related bone disease, and 16 because of iron overload. A control group of 193 patients on maintenance hemodialysis but without desferrioxamine was used. No difference was found in the incidence of septicemia or of all bacterial infections between the patients with aluminum-related bone disease treated with desferrioxamine and the control patients (0.12 vs. 0.12 septicemia per patient-therapy-year, p greater than 0.05; 0.23 vs. 0.26 bacterial infections per patient-therapy-year, p greater than 0.05). The incidence of septicemia in patients treated with desferrioxamine for iron overload, however, was almost three times that in the control patients (0.36 vs. 0.12 septicemia per patient-therapy-year, p less than 0.01). To assess the effect of iron overload itself, we determined the frequency of bacterial infection in patients on regular hemodialysis who have never received desferrioxamine. These were subdivided into three groups according to serum ferritin level which indicated normal or low iron stores (Group I: serum ferritin 10-330 micrograms/l, n = 125), moderate (Group II: serum ferritin 331-1000 micrograms/l, n = 49) or more advanced iron overload (Group III: serum ferritin 1001-2000 micrograms/l, n = 10). Compared to patients with normal or low serum ferritin levels (Group I), we found a significantly higher rate of bacterial infection among patients in Group II compared with Group I (0.18 vs. 0.34 infections per patient-therapy-year, p less than 0.05) and Group III compared with Group I (0.18 vs. 0.58 infections per patient-therapy-year, p less than 0.01). These results suggest that treatment with desferrioxamine does not favour the development of septicemia or bacterial infection independently of iron overload and that iron overload itself may predispose patients on regular hemodialysis to bacterial infection.     

The importance of bacterial sepsis in intensive care unit patients with acquired immunodeficiency syndrome: implications for future care in the age of increasing antiretroviral resistance

OBJECTIVE: To describe the clinical characteristics and outcomes of patients with acquired immunodeficiency syndrome (AIDS) admitted to the intensive care unit (ICU). DESIGN: An observational cohort study with retrospective chart review. SETTING: ICU of an urban university medical center. PATIENTS: Consecutive ICU admissions of patients with AIDS at an urban university medical center between December 1993 and June 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded ICU admission diagnosis, clinical characteristics, and outcome. Among 129 ICU admissions of patients with AIDS, 102 (79%) were admitted for infections, of which (45%) had infections caused by bacteria. Pseudomonas aeruginosa, Staphylococcus aureus, and other enteric pathogens were the most frequent isolates. Pneumonia accounted for 65% of 102 admissions for infections. Overall hospital mortality was 54%, but mortality was higher (68%) for patients with bacterial sepsis. Neutropenia was associated with differences in unadjusted survival rates, whereas CD4 counts were not. Independent predictors of hospital mortality included increasing acute physiology scores and severity of sepsis. CONCLUSIONS: In our ICU, among patients with AIDS, sepsis resulting from bacterial infection is now a more frequent cause of admission than Pneumocystis carinii pneumonia. Severity of illness and the presence of severe sepsis were the clinical predictors most associated with increased mortality. Patients who are not receiving or responding to highly active antiretroviral therapy may become as likely to be admitted to an ICU with a treatable bacterial infection as with classic opportunistic infections. Therefore, broad-spectrum empirical antibacterial therapy is particularly important when the etiology of infection is uncertain.     

Hyperaluminaemia in critically ill patients: role of antacid therapy and impaired renal function

A significant rise in serum concentrations of aluminum was demonstrated in 23 patients prophylactically treated with the antacid magaldrate, whereas no increase in serum aluminium was observed in another 26 critically ill patients, in whom the use of antacids was avoided. In parallel, urinary excretion rates of aluminum rose to values close to maximum 72 h after antacid therapy had been started. Hyperaluminaemia was most marked in patients with acute renal failure undergoing continuous haemofiltration, but a significant increment in serum aluminium was also noted in patients with impaired renal function in the predialytic state. In the latter group and in patients with normal renal function there was a significant negative correlation between urinary excretion rates of aluminium and creatinine clearance after 48 h of treatment suggesting an enhancement of gastrointestinal absorption of aluminium in the presence of chronic renal failure. Maximum serum concentrations of aluminium did attain critical values in some patients with acute renal failure, but no overt signs of aluminium toxicity were noted. However, in light of both, possible subtle toxicity and enhanced absorption of aluminium in critically ill patients with renal failure, the prophylactic use of antacids in this setting should be re-evaluated cautiously.     

Infectious complications of advanced cancer

 We present a retrospective study of the frequency, pattern, and management of infections in advanced cancer. Three hundred ninety-three patients were admitted to an acute care palliative medicine unit in an 8-month period for evaluation and palliation of cancer-related symptoms and complications. One hundred fifteen had at least one positive bacteriological culture, and 100 of these patients were evaluable. One hundred fifty-two infections and 192 isolates were identified. Sixty-eight patients had polymicrobial infections. Sixty-six patients had urinary tract infections. Forty-one were found to have multisystemic infections. Eighty-one had invasive devices; 32 had more than one invasive device. Fifty-three were taking corticosteroids at the time of infection. Only 3 were neutropenic. Urinary tract infections were significantly more common in those taking corticosteroids. The median duration of antibiotic treatment was 11 days and the median hospital stay, 14 days. Twenty-eight patients died in the hospital; 10 of those who died had lung cancer, which was a statistically significant observation. In conclusion, infections are an underrecognized but common complication in nonneutropenic hospitalized patients with advanced solid tumors. Urinary tract infections appear to be associated with the use of corticosteroids. Lung cancer patients are at greater risk for fatal infections. Infections increase morbidity in debilitated patients with solid tumors, are a frequent cause of hospital admission, and are associated with significant mortality. Published online: 31 May 2000     

Silicon and aluminium and their inter-relationship in serum and urine after renal transplantation

Abstract. The present study was undertaken to establish the relationship between serum and urine silicon and improve renal function and examine whether the increased urinary excretion of aluminium observed after successful renal transplantation was associated with silicon. The changes in silicon and aluminium concentrations in serum and urine were measured in 15 patients for a period of up to 17 days following a first renal transplant. Serum silicon, unlike aluminium, progressively decreased with improving renal function and was significantly positively correlated with serum aluminium but not with the silicon excretion. The urine excretion of aluminium peaked between 4–8 days post-transplantation and was highly significantly positively correlated with urine silicon. The individual patient fractional excretion profiles of aluminium and silicon were variable but in general gave significant positive correlations suggesting that the elements may be cleared by the kidney through a common mechanism or as a chemical species, possibly an hydroxyaluminosilicate. If soluble silicon can chemically interact with aluminium in vivo it may, as in the biosphere, be important in the control of aluminium toxicity and eventual detoxification. Thus, elevated serum silicon concentrations may help to alleviate aluminium toxicity in end-stage renal disease and assist in the rapid clearance of aluminium seen after kidney transplantation.     

Polymorphonuclear leukocyte inclusions and impaired bacterial killing in patients with Felty's syndrome.

Humoral factors, phagocytosis, bactericidal capability, and ultrastructural morphology of blood polymorphonuclear leukocytes were investigated in 10 patients with Felty's syndrome. Five patients had suffered significant bacterial infections in the past two years while five other patients had not had bacterial infections. The patients with infections had higher concentrations of serum cryoglobulins, and their neutrophils contained immunoglobulin inclusions as seen by immunofluorescent and electron microscopy. Additionally, leukocytes from these patients showed decreased ability to kill Staphylococcus aureus and a minor defect in phagocytosis. There was a generalized subcellular disorganization of these inclusion containing neutrophils and a slower than normal release of lysosomes. Several of the above abnormalities may contribute to an increased susceptibility to bacterial infections in patients with Felty's syndrome.     

Variability of steady-state digoxin kinetics during administration of tablets or capsules

An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug. It is predicted that such a preparation would show reduced within- and between-patient variability in absorption, as most studies in normal subjects have shown reduced intersubject variation with the capsule. We tested inter- and intrapatient variability during 4-week periods of dosing with digoxin capsules and tablets in 28 subjects with cardiac disease. In the overall group there were no significant differences between the formulations at steady state in between-patient variability in trough serum digoxin concentrations or 24-hour urinary digoxin excretion. Within-patient variability in urinary digoxin excretion was somewhat lower for the capsules. In a subgroup of six patients who excreted significant amounts of cardioinactive bacterial metabolites (digoxin reduction products [DRP]), the mean (+/- SD) percent urinary DRP excretion was less (p less than 0.05) during capsule (20.5% +/- 15.1%) than tablet (34.4% +/- 10.9%) dosing. Within-patient variability in urinary DRP excretion was much greater after tablets than capsules. Certain subgroups of patients should benefit from the enhanced bioavailability of digoxin capsule preparations.     

高血压脑出血96例围手术期护理

目的:研究高血压脑出血患者围手术期护理措施。方法:将高血压脑出血手术患者96例,采用颅内血肿清除、去骨瓣减压,脑室内引流和单纯钻孔引流等手术方式治疗,术后精心护理。结果:术后存活80例,死亡9例,放弃治疗7例。其中并发偏瘫10例,上消化道出血8例,肺部感染7例,泌尿系感染5例,颅内感染3例。结论:手术是治疗高血压脑出血的有效手段,细致周密的护理是预防术后并发症,降低患者病死率和致残率的重要因素。     

Trace element alterations in infectious diseases

Trace elements like copper, zinc, iron and selenium have a significant influence on the function of the immune system. We studied plasma levels of trace elements in 53 patients with acute bacterial and viral infections. In bacterial infections (septicaemia, pneumonia, erysipelas and meningitis) the plasma concentrations of selenium, iron and zinc were decreased. Plasma copper was unchanged in patients with erysipelas, but increased in other types of bacterial infections. Although the patients with viral infections showed similar shifts of the trace elements as were observed in patients with bacterial infections, the changes were not as pronounced. A plasma selenium value below 0.8 mumol/l was found in only 6% of the patients with viral infections in contrast to 63% of the patients with septicaemia or 57% of the patients with pneumonia. Furthermore, in viral infections 60% of the zinc values were below the mean level of 12.8 mumol/l observed in healthy controls as compared with 90% of the values in patients with sepsis or 92% of the values in patients with pneumonia. The onset of change in trace elements occurred within a few days and persisted for several weeks. These changes seem to be non-specific and are independent of the agent causing infection. The different types of infections were followed by changes in most of the plasma proteins which are known to be associated with an inflammatory reaction. The changes in plasma proteins were most pronounced in patients with sepsis and pneumonia. Patients with sepsis having a high degree of inflammation did not show a positive correlation between the severity of the disease--as judged by plasma proteins--and the alterations of trace elements.     

Critically ill patients with cancer and sepsis: clinical course and prognostic factors

Purpose

The purposes of this study were to evaluate the clinical course and to identify independent predictors of mortality in patients with cancer with sepsis.

Materials and Methods

This is a secondary analysis of a prospective cohort study conducted at an oncological medical-surgical intensive care unit. Logistic regression was used to identify predictors of hospital mortality.

Results

A total of 563 patients (77% solid tumor, 23% hematologic malignancies) were included over a 55-month period. The most frequent sites of infection were the lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock. Gram-negative bacteria were responsible for more than half of the episodes of infection; 38% of patients had polymicrobial infections. Intensive care unit, hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In multivariate analyses, sepsis in the context of medical complications; active disease; compromised performance status; presence of 3 to 4 systemic inflammatory response syndrome criteria; and the presence of respiratory, renal, and cardiovascular failures were associated with increased mortality. Adjusting for other covariates, patients with non–urinary tract infections, mostly represented by patients with pneumonia and abdominal infections, had worse outcomes.

Conclusions

Sepsis remains a frequent complication in patients with cancer and associated with high mortality. Our results can be of help to assist intensivists in clinical decisions and to improve characterization and risk stratification in these patients.     

Infections in a Renal Unit

Five hundred and thirty-three patients in the Oxford renal unitwere reviewed to determine the incidence of infection in onecalender year. There were 310 patients who received dialysis,53 with acute renal failure and 211 with chronic renal disease.Renal transplant patients were not included in the study. Apartfrom infections related to dialysis access, patients on maintenancehaemodialysis or continuous ambulatory peritoneal dialysis developedfew serious infections unless they had another disease causingsuppression of immune function. A total of 97 urinary tractinfections were seen; in patients with chronic renal diseasenot receiving dialysis the incidence of urinary tract infectionwas significantly associated with increasing uraemia, with diabetes,and with treatment with azathioprine or cyclophosph amide. Inpatients with acute renal failure, Gram-negative septicaemiaand fungal infections were important causes of morbidity andmortality, but cardiovascular disease caused 42 per cent ofthe deaths unlike results from other series where sepsis hasbeen by far the commonest cause of death.