Ciprofloxacin in critically ill children.

Data regarding the use of fluoroquinolones in critically ill children are scarce. We present our experience regarding the use of ciprofloxacin in this specific patient population. We prospectively identified all paediatric patients who received ciprofloxacin treatment in the intensive care unit of the tertiary care P. & A. Kyriakou Children's Hospital during a three year period (2005 to 2008). Eighteen paediatric patients (mean age 23 months, 12 females) who received intravenous ciprofloxacin were identified. Various underlying diseases, including malignancy and immunodeficiency, were observed. None of the evaluated patients had cystic fibrosis. Fourteen patients had bacteraemia (mainly caused from Gram-negative pathogens), one had Stenotrophomonas maltophilia pneumonia, while no pathogen was identified in three patients. The latter patients received ciprofloxacin due to the severity of their clinical manifestations. All patients with microbiologically documented infections recovered. Three deaths attributed to the underlying diseases were noted. Within a 10-day follow-up, two cases of diarrhoea, one case of vomiting and one case of reversible supraventricular tachycardia were noted. No case of QT prolongation was noted. The short-term follow-up hampered any assessment of joint and cartilage toxicity, potentially associated with ciprofloxacin treatment. Our study suggests that ciprofloxacin may be a useful option for critically ill children without cystic fibrosis. Even though firm conclusions regarding the safety profile of ciprofloxacin in critically ill children could not be drawn, our study provides useful information regarding short-term adverse events associated with ciprofloxacin.

Cyclosporine and its metabolites before and 2 h post-dose: comparative measurements of a monoclonal and a polyclonal immunoassay.

The aim of the study was to investigate the better accuracy of the 2-h post-dose (C2) levels of cyclosporine (CyA), compared with the pre-dose (C0) levels and to evaluate the results measured by a monoclonal or a polyclonal immunoassay. The parent compound of CyA in C2 (monoclonal2) was measured in 53 kidney transplant patients by the monoclonal fluorescence polarization method, as well as the parent compound plus metabolites (polyclonal2) by the polyclonal fluorescence polarization method. Also, the parent compound was measured in 21 of the patients for the C0 (monoclonal0), whereas the parent compound plus metabolites in 36, for the C0 (polyclonal0). As level of metabolites was considered the difference between polyclonal and monoclonal values (polyclonal-monoclonal), either in C0 (metabolites0) or in C2 (metabolites2). The ratio polyclonal2/monoclonal2 gave a mean value of 1.7+/-0.2 (mean+/-SD), whereas the mean value of the ratio polyclonal0/monoclonal0 was 2.3+/-0.6, with almost double variation. The mean value of the ratio metabolites2/monoclonal2 was 0.7+/-0.2 and of the ratio metabolites0/monoclonal0 was 1.3+/-0.6. The difference between the two ratios is very significant (p = 0.000001) and they are not correlated with each other (r = 0.18, p = 0.44). The measurements of monoclonal0 and polyclonal0 or monoclonal2 and polyclonal2 are very significantly correlated (r = 0.94, p = 0.000001 and r = 0.97, p = 0.000001, respectively). In C0 the proportion of metabolites is higher than in C2, with a double variation, as the degree of metabolism is diverse. Consecutively, in monoclonal methods, as cross-reactions occur with metabolites, it is more accurate to use the C2 measurement for the evaluation of CyA. The application of both methods, the polyclonal and the monoclonal, could be a useful tool as it gives an estimation of metabolites whose degree of contribution to the immunosuppressive result is difficult to ascertain. Finally, if for reasons of clinical experience, the polyclonal method is used, then the mean therapeutic levels of polyclonal2 are 1.5-1.7 compared with monoclonal2.

Effect of low-dose oral erythromycin on gastric aspirates in ventilated neonates less than 32 weeks of gestation. Preliminary results.

In this prospective study, the 24-hour gastric aspirate volume was carefully recorded before, 24 and 48 h after administering 1.7 mg/kg/8-hourly of oral erythromycin to 16 ventilated neonates less than 32 weeks of gestation. Their median gestational age was 28.5 weeks (range 23-31 weeks), their median birthweight was 1,045 g (range 690-1,560 g) and the median day of life at which erythromycin was commenced was 9.5 days (range 4-16 days). Prior to administering erythromycin median 24-hour gastric aspirate volume, expressed as a percentage of the milk volume given over the same period, was 38.5% (range 20.0-100%). It was significantly lower 24 h (median 12%, range 0-41%, p = 0.0004) and 48 h (median 5%, range 0-21%, p = 0.0004) after commencing erythromycin. There was also significant reduction of gastric aspirate volume between 24 and 48 h after commencing erythromycin (p = 0.0024). Milk volume increment over the same period was not significant (p = 0.1022). These preliminary results warrant further evaluation through a randomised controlled trial.

Mild dilatation of renal pelvis in term neonates with urinary tract infection.

The purpose of this study was to assess the incidence and evolution of mild dilatation confined to the renal pelvis in term neonates with urinary tract infection developing within 2 weeks from birth. Twenty-two neonates with mild dilatation of the renal pelvis out of 180 neonates with urinary tract infection were identified giving an incidence of 12.2% for this finding. Male to female ratio was 6.3:1. The left kidney was twice as frequently involved (68 vs. 32%). At follow-up, the dilatation had disappeared in 20 neonates (90.9%) by a mean age of 2.7 years with only one neonate developing two further episodes of urinary tract infection in the infantile period. No other morbidity was noted.

Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) varies and there is considerable controversy as to which factors are of importance in determining prognosis or response to therapy. The aim of this study was to identify clinical, pathological or immunohistochemical features at biopsy that could identify patients with progressive disease who might benefit from treatment, and predict long-term outcome. METHODS: The clinical and pathological findings of 33 adult patients with primary FSGS were retrospectively analysed in order to identify features at biopsy that could be predictive of outcome or response to treatment. For this purpose an immunohistochemical study was also performed, using monoclonal antibodies against intracellular adhesion molecules-1, C5b-9, alpha 3 beta 1 integrin, alpha-smooth-muscle actin (SMA), and TGF-beta1. RESULTS: At biopsy 17 patients (51%) were nephrotic and 16 (49%) non-nephrotic. Of the nephrotic patients, 11 were treated and six received only symptomatic therapy. Initial treatment with prednisolone (Pred) for 6-12 months (average 9 months) resulted in remission in 64% of nephrotic patients. To those with partial or no response, cyclosporin (CsA) or cyclophosphamide was given. At the end of follow-up (mean 57 months) three nephrotic patients (28%) were in complete remission, six (54%) in partial remission, and two (18%) did not respond to the treatment. In the seven treated non-nephrotic patients, Pred induced a complete remission in two (28%), a partial remission in three (44%), while two patients (28%) did not respond. Plasma creatinine remained stable in nephrotic patients who responded and it almost doubled in non-responders. Plasma creatinine also remained unchanged in treated non-nephrotic patients who responded to Pred, while two non-responders reached end-stage renal disease (ESRD). In contrast, 50% of untreated nephrotic patients and 67% of untreated non-nephrotic patients progressed to ESRD. Multivariate analysis showed only age and plasma creatinine at biopsy to have an independent predictive value for renal survival in nephrotic patients. This analysis also demonstrated that only the severity of interstitial fibrosis predicted the response to the treatment. In addition, the tubulointerstitial but not the glomerular expression of C5b-9, alpha 3 beta 1 integrin, alpha-SMA, and TGF-beta1 was significantly more extensive in non-responders and correlated with renal function at biopsy. However, only tubulointerstitial expression of TGF-beta1 independently correlated with the degree of renal function impairment at biopsy, but none of the above markers independently predicted renal survival or response to therapy. CONCLUSIONS: Nephrotic patients with FSGS may benefit from a more prolonged course of Pred. Nephrotic patients responding to treatment have a significantly better renal survival than non-responders. Age and plasma creatinine at biopsy are independent risk factors leading to ESRD. The severity of tubulointerstitial fibrosis is predictive of response to therapy.

Adult-onset idiopathic nephrotic syndrome associated with pure diffuse mesangial hypercellularity.

BACKGROUND: Pure diffuse mesangial hypercellularity (DMH), in its primary form, is a relatively rare histological finding and few data exist in the literature regarding its clinical course and prognosis in nephrotic adults with this diagnosis. METHODS: We retrospectively analysed the clinical and histological data of 28 adult nephrotic patients (13 male) with this diagnosis with regard to response to the treatment, outcome and prognostic indicators. RESULTS: Of 25 patients treated with prednisolone (Pred), nine (36%) showed complete remission (CR) of proteinuria, eight (32%) partial remission (PR) and eight (32%) did not respond at all (NR). The combination of cyclosporin treatment with prednisolone of those with PR or NR produced one further complete and two partial remissions. At the end of follow-up (mean 64 months), 10 patients (40%) were in CR, nine (36%) in PR and six (24%) were NR and remained nephrotic. Renal function remained unchanged in patients with CR or PR. In contrast, the six non-responders progressed to end-stage renal disease (ESRD). Compared with non-responders, patients who responded to Pred were older and had normal renal function at presentation. This group also had less mesangial sclerosis and severe tubulointerstitial fibrosis and none showed synechiae with Bowman's capsule. IgM mesangial deposits were observed in 22% of patients with CR in response to Pred, in 37% of those with PR and in 100% of non-responders, who finally progressed to ESRD. A multivariate analysis of clinical and histological features at biopsy showed persistent nephrotic syndrome (P<0.001), the severity of DMH (P<0.03) and the presence of mesangial IgM (P<0. 01) to have independent predictive value for ESRD. This analysis also demonstrated that only mesangial sclerosis (P<0.03) and the presence of mesangial IgM (P<0.002) independently predicted the response to therapy. CONCLUSIONS: DMH associated with idiopathic nephrotic syndrome is a heterogeneous entity. Patients who respond to therapy (completely or partially) have a benign course similar to that of minimal change nephrotic syndrome. They are usually older and have normal renal function at presentation, whereas 'sclerotic' lesions are less frequent findings in initial biopsies. Non-responders tend to be younger and progress to ESRD. Most of them have impaired renal function at first assessment and more prominent 'sclerotic' lesions on initial biopsies. Mesangial IgM is an independent marker of poorer response to treatment and progression to ESRD but it lacks specificity.

Treatment of gram-negative bacterial meningitis in term neonates with third generation cephalosporins plus amikacin.

The aim of this retrospective study was to evaluate the clinical efficacy in terms of mortality and long-term morbidity of third generation cephalosporins and amikacin in combination for the treatment of gram-negative bacterial meningitis in a homogeneous group of neonates. A 15-year experience (1983-1997) with 72 term neonates without central nervous system anomalies and with gram-negative organisms grown in their cerebrospinal fluid treated with the above combination of antibiotics is presented. All isolated organisms were sensitive to cefotaxime or ceftazidime and to amikacin but 80% were resistant to ampicillin. The predominant infecting organism was Escherichia coli (68.0%) which was sensitive to both cefotaxime and amikacin in all cases but resistant to ampicillin in 48% of cases. Survival at discharge was 97.2% but ultimate survival was reduced to 94.4%, as 2 patients died a few months following discharge of conditions unrelated to meningitis. Ventriculitis was diagnosed in 10 neonates (13.8%). Among survivors, 1 neonate (1.3%) developed hydrocephalus needing shunting and 1 neonate (1.3%) with Proteus mirabilis developed a brain abscess with relapse of meningitis which was successfully treated with a 6-week course of chloramphenicol. At follow-up at an age greater than 6 months, 91.1% of the surviving infants were normal, while 92.3% of survivors at an age greater than 6 years were normal and attended normal school. These results, despite any reservations due to the nature of the study (retrospective, uncontrolled study), strongly support the use of third generation cephalosporins and amikacin in combination for the treatment of neonatal gram-negative bacterial meningitis.

Neonatal neurological examination in infants with hypoxic ischaemic encephalopathy: correlation with MRI findings.

Neurological examination and magnetic resonance imaging were performed in the neonatal period in 58 full-term infants who presented with hypoxic-ischaemic encephalopathy. The aim of this study was to evaluate the patterns of neurological abnormalities and their correlation to brain lesions on MRI. The prognostic value of the neurological examination performed at different times in the neonatal period was also evaluated. Our results showed that specific clinical patterns can be observed in infants with HIE and these can be related to the pattern of lesion on brain MRI. In particular, while infants with normal MRI or minimal changes tend to show only minor tone abnormalities after the first week of life, infants with more severe lesions such as basal ganglia lesions show persistent and diffuse neurological abnormalities. Infants with white matter changes but intact basal ganglia show a different clinical pattern with improved sucking reflex and behaviour and less severe tone abnormalities. Our results also suggested that the neurological examination performed after the second week of life is a reliable indicator of outcome in these infants.

The effect of membrane permeability on ESRD: design of a prospective randomised multicentre trial.

The different permeability of high-flux and low-flux dialysis membranes results in different removal capacity, particularly for uremic toxins of middle and large molecular weight. High-flux dialysers have been evaluated in clinical and epidemiological studies for their effect on mortality, morbidity, dialysis-related amyloidosis, nutritional status, response to erythropoietin treatment, dialysis tolerance and the preservation of residual renal function. Many of these studies, however, lack a prospective design and randomised treatment allocation, or have too few patients and too short a follow-up. Therefore, this clinical trial was designed to prospectively investigate the long-term effect of membrane permeability on clinical outcome in a larger number of patients. The primary objective is to compare the effect of membrane permeability on mortality of patients on bicarbonate hemodialysis and treated with a minimum dialysis dose. Patients included in the study should have been on hemodialysis for no longer than one month and have serum albumin 4 g/dl or lower. Patients will be randomised to either the experimental or the control group. During the four-week run-in period the treatment parameters will be established in order to achieve the required dialysis dose. During the maintenance period of three to five years regular visits are scheduled to record clinical and laboratory parameters, to measure Kt/V and to adapt the treatment parameters. Altogether a minimum of 660 patients should be enrolled within a two-year recruitment period.

The use of ultrasonography and linkage studies for early diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

To define possibly affected members of 69 families and to identify the factors influencing the progression of autosomal dominant polycystic kidney disease (ADPKD), 276 subjects at risk of having inherited the mutant gene underwent ultrasonographic scanning (US), using an ultrasound real-time scanner. At a mean age of 26 +/- 12 years (range 4-71), 85/276 individuals (31%) presented ultrasound evidence of the disease (at least two cysts in one kidney and one cyst in the other) (US: positive), while only 19/85 (22%) had one or more manifestations of ADPKD prior to diagnosis. The prevalence of the disease in subjects at risk aged < 30 years was 53/154 (34%), while hepatic cysts were also detected in 7/85 ADPKD probands (8%) (five females) at a mean age of 40 +/- 6 years (range 30-45) and their frequency correlated with the number of pregnancies. History was proved to be important in suspecting the disease since symptoms were more common in US positive as compared to negative subjects (22% vs 6%, p < 0.001). On the other hand, physical examination and routine laboratory data at presentation revealed abnormal signs mainly in US positive individuals aged 30-39 years. Forty ADPKD families met the criterion for genetic study (at least two members affected) but in three of them (7.5%), no linkage to DNA-markers for the short arm of chromosome 16 was detected ("unlinked" or ADPKD2). DNA-analysis in the rest 37 "linked" (ADPKD1) families identified the gene-carrier state in 18/123 (15%) US negative subjects at risk, at a mean age of 13 +/- 7 years (range 3-25). There were significantly more US positive subjects aged > or = 30 years in ADPKD2 as compared to ADPKD1 families (83% vs 35%, p < 0.05) suggesting that the progression of the disease is slower in the former families. During a 5-year follow-up, 6/18 gene-carriers (33%) had already developed distinct renal cysts on US, at a mean age of 20 +/- 9 years (range 8-29). On the contrary, none of the ADPKD1 non-carriers and the US negative ADPKD2 subjects had shown any ultrasound findings of cystic renal disease at that period.

Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study.

OBJECTIVE: The aim of this study was to identify prognostic factors in newborns with cerebral infarction. DESIGN: Antenatal and perinatal factors and early clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings were compared with neurodevelopmental outcome in 24 children with evidence of cerebral infarction on neonatal MRI. RESULTS: Out of 24 infants, 19 had an infarction in the territory of a major cerebral vessel and 5 in the borderzone between cerebral arteries. Neuromotor outcome was normal in 17 and abnormal in 7 infants. Of these 7 infants, 5 infants showed a definite hemiplegia, whereas the other 2 showed some asymmetry of tone or function but no definite hemiplegia. None of the adverse antenatal or perinatal factors was significantly associated with abnormal outcome. Neonatal clinical examination was also not always predictive of the outcome. The extent of the lesion on MRI was a better predictor. In particular, it was the concomitant involvement of hemisphere, internal capsule and basal ganglia that was always associated with an abnormal outcome whereas the involvement of only one or two of the three tended to be associated with a normal outcome. EEG was also very helpful. Abnormal background activity either unilateral or bilateral was found in 6 infants and 5 out of 6 developed hemiplegia. In contrast, the presence of seizure activity in presence of a normal background was not related to abnormal outcome. CONCLUSIONS: Early MRI and EEG can help to identify the infants with cerebral infarction who are likely to develop hemiplegia.

Integrin alpha4beta1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow.

Adhesion and stabilization of circulating tumor cells to endothelial cells in target blood vessels play an important role in the complex process of metastasis. We examined the cell surface receptors involved in the liver-metastatic adhesive interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE cell monolayers under flow. In contrast, RAW117 cells required a significantly lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb significantly decreased the extent of adhesion compared to that of the control, without affecting adherent cell stabilization times. Blocking the alpha4 integrin subunits present mainly on RAW117 cells produced similar results to those previously observed with anti-VCAM-1 mAb. Although constitutively present mainly on the surfaces of RAW117 cells, MAdCAM-1 and beta7 integrin subunit do not appear to play a role in either the arrest or stabilization of RAW117 cells on HSE cell monolayers. However, blocking the beta1 integrin subunit on the RAW117-H10 cells reduced adhesion to the same extent as anti-alpha4 and anti-VCAM-1 treatments. These observations suggest that an interaction of integrin alpha4/beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis.

Acute renal failure--which treatment modality is the best?

Despite the progress in animal research concerning the pathophysiology and the progress in clinical practice regarding the methods of therapy, the incidence and mortality of acute renal failure remain high, especially when other organs are involved. New pharmacological interventions have led to the perspective that in the near future it may be possible to prevent and/or ameliorate this devastating syndrome. Continuous dialysis therapy and the selection of a biocompatible membrane may possibly help the critically ill patient especially when parenteral nutrition and correction of electrolyte and acid-base disturbances are important. Nevertheless, more solid data are needed and one should take into consideration that acute renal failure is a multifactorial syndrome. The type of dialysis itself is not the only matter which has to be evaluated since the mortality rate can be correlated with the number of involved organs before or after the initiation of acute renal failure and with the severity of the original disease. In clinical practice, a large number of prospective studies and more sophisticated statistical methodology are needed in order to evaluate the proper treatment modality.

Emotional support of cancer patients: the nursing approach.

The present study attempts to classify cancer patients' psychologic responses in order of importance, and to identify the role of the oncology nursing staff in the moral support of these patients. We want to emphasize the significant role of the nursing staff because until 1990, Greece had no specialization in the field of oncology nursing. After the initial diagnosis of cancer, the patient was considered as emotionally depressed. Our sample consisted of 120 cancer patients from the southwestern regions of Greece. From our research, we concluded that the factors generally characterizing cancer patients, in order of priority, are (a) moral support from family and friends (p < 0.0001), (b) psychologic reactions after some months (p < 0.0001), (c) sex (p = 0.0006), (d) age (p < 0.0001), (e) marital status (p < 0.0001), and (f) psychologic reactions during the first days following diagnosis (p = 0.018) because of the shock experienced. More specifically, we wish to stress the absence of the consulting role on the part of the nursing staff. This finding is worth the keen attention of consultants on health matters. Nurses have a great deal to contribute to the emotional care of cancer patients, and are puzzled about the reasons why they are not asked to participate in this important function.

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Is membranous nephropathy only a glomerular disease?

Tubulointerstitial lesions represent not only a constant component of the pathology of a "classical" glomerular disease such as idiopathic membranous nephropathy but also the most important prognostic indicator and a new "target" for its treatment. Proper "quantification" of the cellular events occurring within the interstitium may enable us to accurately assess the amount of disease activity and identify patients who might benefit from treatment.

Renal transplantation in adults with autosomal recessive inheritance of hemolytic uremic syndrome.

When hemolytic uremic syndrome (HUS) is occasionally inherited in an autosomal recessive mode, this occurs mainly in infants and children. We describe four families in which two adult siblings were affected with HUS in each kindred. HUS first occurred between the ages of 19 to 36 years, and the intervals between the onset of HUS in each sibling pair ranged from 6 months to 6 years. None of the patients had a typical prodrome of bloody diarrhea, and one had a recurrence of HUS before transplantation. All eight patients developed renal failure requiring dialysis and transplantation, and seven patients received kidney transplants. Donor kidneys were from parents, siblings, and cadavers. The initial renal transplants were performed from 6 months to 6 years after the onset of the syndrome. HUS recurred in six of the seven patients 2 weeks to 6.5 years after transplantation regardless of the interval between the onset of HUS and transplantation, the origin of the allograft, or the use of cyclosporin A. The only marker for autosomal recessive HUS is the occurrence of the syndrome in a second sibling several months to many years after its occurrence in the proband. In patients with the autosomal recessive form of HUS, the risk for a recurrence in an allograft is high regardless of the source of the kidney.

Increased glomerular and interstitial LFA-1 expression in proteinuric immunoglobulin A nephropathy.

The cell populations infiltrating the kidneys and the LFA-1 expression were studied in renal biopsy specimens from patients with proteinuric (n = 15, group 1) and non-proteinuric (n = 12, group 2) immunoglobulin A nephropathy. Both groups were matched for age and renal function at the time of biopsy. Proliferative glomerular changes were more commonly see in group 1. Both groups had similar numbers of intraglomerular and interstitial total leukocytes, monocytes/macrophages, and T cells (P = NS). However, glomerular LFA-1 alpha- and -beta-positive cells were significantly higher in group 1 (2.3 +/- 0.2 and 3.3 +/- 0.1 per glomerulus) than in group 2 (0.2 +/- 0.08 and 0.5 +/- 0.05 per glomerulus) (P < 0.005 and P < 0.01, respectively). Group 1 had much higher interstitial LFA-1 alpha- (109 +/- 20/mm(2)) and -beta-positive cells (157 +/- 40/mm(2)) in comparison with group 2 (29 +/- 12/mm(2) and 42 +/- 17/mm(2)). (P < 0.005 and P < 0.01, respectively). No association between glomerular and interstitial LFA-1-positive cells was seen. In addition, tubular HLA-DR expression was higher in group 1 (29 +/- 6/mm(2)) than in group 2 (9 +/- 2/mm(2)) (P < 0.005), but the interstitial HLA-DR-positive cells were similar in both groups. There was a significant association between interstitial LFA-1 alpha- and -beta-positive cells and tubular HLA-DR expression in group 1 (P < 0.01 and P < 0.005, respectively) but not in group 2. Interestingly, the extent of interstitial but not glomerular LFA-1-alpha and -beta expression was highly related to the degree of proteinuria in group 1 (P < 0.01 and P < 0.002, respectively). In conclusion, proteinuria in immunoglobulin A nephropathy is associated with increased LFA-1 expression by glomerular and interstitial infiltrating cells. However, interstitial but not glomerular LFA-1-positive cells are strongly related with the degree of urinary protein excretion. The exact link between LFA-1 expression and proteinuria needs further investigation.