Urinary albumin excretion and transcapillary escape rate of albumin in malignancies

Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined as ≥20 μg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by⁵¹Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 μg/min (range 6–510 μg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM) stage II–IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I). Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary escape rate of albumin was 5.5%/h (range 2–8%/h) and this level is comparable with values in healthy subjects. There was no significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated by the transcapillary escape rate of albumin, suggests an overal unaffected capillary permeability and increased urinary albumin loss appears to be an isolated renal phenomenon in cancer patients.     

Neonatal subgaleal haematoma: Associated risk factors, complications and outcome

Objective : To describe the obstetric and perinatal factors, in particular the method of delivery, associated with development of a subgaleal haematoma (SGH) and to determine the outcome of survivors with this type of birth trauma. Methodology : Perinatal and obstetric data were retrospectively reviewed for 37 infants admitted to the neonatal unit of the sole tertiary paediatric referral hospital in Western Australia with an SGH, over a 24 year period from 1970 to 1993. These data were compared to data for all Western Australian births. The long-term outcome was obtained through medical and private paediatric records for 26 of these infants. Results : All except one of the neonates had instrumental deliveries; 89% had a vacuum extractor applied to the head at some stage of delivery compared to 10% of the general population of births in Western Australia. There was also a significantly increased risk of failure of attempted vacuum extraction. Of the cases where a vacuum extraction was attempted, 45% also had forceps applied to the head. Coagulopathy was associated with the severity of the SGH. There was also a high frequency of occurrence (40%) of associated head trauma such as intracranial haemorrhage, skull fracture and cerebral oedema, as well as neonatal encephalopathy (73%). The occurrence of these associated features did not correlate significantly with the severity of SGH. Minor complications of SGH included jaundice and facial bruising. There was an excess mortality associated with SGH; however, the long-term outcome for neonatal survivors with this disorder was good. None of the cases studied subsequently developed cerebral palsy or intellectual disability, and minor neurological sequelae only were documented in four infants. Conclusions : SGH is an uncommon type of birth trauma, and is associated with delivery or attempted delivery by vacuum extraction. The most commonly associated clinical problems were hypovolaemia and coagulopathy. The long-term outcome for neonates with this condition is good.     

Concordance between qualitative and quantitative cultures in burned patients. Analysis of 2886 cultures

OBJECTIVE: To determine the concordance between superficial cultures (SC) and quantitative cultures (QC) in the diagnosis of wound infection in burn patients. METHOD: Sample: All SC and QC taken from the same patient, site and during the same surgery were analysed. Variables: On the SC, the microorganism (MO) and its amount defined subjectively by the microbiologist was recorded (negative, very low, low, regular and abundant). On the QC, the MO and its amount were expressed as colony forming units per gram of tissue (CFUs/g). Statistics: Kappa index of agreement beyond chance; Wilcoxon and Kruskall-Wallis for continuous variables and chi(2) for categorical variables were used with a p<0.05 indicating statistical significance. RESULTS: One thousand four hundred and forty three pairs of cultures were analyzed. The concordance between SC and QC (Kappa index) was 52%. On the SC, only when the microbiologist subjectively informed "abundant" MOs there was a significant difference (p<0.0001). There were 6.1% of QCs with more than 10(5) CFUs/g and the most frequent MOs isolated were: S. aureus (27.9%), E. coli (11.6%), P. aeruginosa (11.6%), E. faecalis (11.6%) and S. epidermidis (7.0%). CONCLUSIONS: SC has a moderate concordance with the QC showing a low reliability between the two methods. The subjective information given by the microbiology technician in the SC is not precise. A study in which the two methods be compared blindly against the reference standard, in a prospective cohort of patients, it is needed to discriminate which of two methods it is the most accurate one determining sensitivity and specificity.     

The presence of glia stimulates the appearance of glycinergic synaptic transmission in spinal cord neurons

Previous studies, using electrophysiological and fluorimetric analysis with a calcium sensitive dye, have shown that 5-7 DIV developing spinal cord neurons displayed high levels of glycinergic transmission. GABAergic and AMPAergic neurotransmission contributed much less to the overall transmission. Here, we show that culturing neurons in absence of a glia cell monolayer reduced the frequency of glycinergic spontaneous IPSCs (0.1 +/- 0.01 Hz), without altering the level of overall transmission (3 +/- 1.1 Hz). The predominant transmission was mediated by GABA(A) receptors (72% of total synaptic events). In addition, combination of bicuculline and CNQX blocked synaptically mediated calcium transients recorded with fluo-3. Furthermore, application of glycine revealed the presence of extrasynaptic receptors in these neurons (25 +/- 6 pA/pF). Culturing neurons on a glial cell monolayer increased the frequency of glycinergic currents (0.4 +/- 0.02 Hz), without changing the amplitude of the current (20 +/- 4 pA). The use of a glia-conditioned media reversed the effect of growing the neurons in a glia-deprived condition. These results indicate that the establishment of glycinergic transmission is dependent on the presence of a glia derived soluble factor. However, functional GlyRs were still able to insert in the neuronal membrane in a glia-independent manner.     

Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. In this study, we examined a large panel of human malignant glioma cell lines and primary cultures of normal human astrocytes for their sensitivity to TRAIL. Of 13 glioma cell lines, 3 were sensitive (80-100% death), 4 were partially resistant (30-79% death), and 6 were resistant (< 30% death). Normal astrocytes were also resistant. TRAIL-induced cell death was characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation. Decoy receptor (DcR1 and DcR2) expression was limited in the glioma cell lines and did not correlate with TRAIL sensitivity. Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5), adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant cell lines expressed 2-fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa (PED/PEA-15). In contrast, cellular FADD-like IL-1beta-converting enzyme-like inhibitory protein (cFLIP) expression was similar in sensitive and resistant cells. Transfection of sense PED/PEA-15 cDNA in sensitive cells resulted in cell resistance, whereas transfection of antisense in resistant cells rendered them sensitive. Inhibition of protein kinase C (PKC) activity restored TRAIL sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be dependent on PKC-mediated phosphorylation. In summary, TRAIL induces apoptosis in > 50% of glioma cell lines, and this killing occurs through activation of the DR pathway. This caspase-8-induced apoptotic cascade is regulated by intracellular PED/PEA-15, but not by cFLIP or decoy receptors. This pathway may be exploitable for glioma and possibly for other cancer therapies.     

Enteral feeding in stable chronic obstructive pulmonary disease patients

OBJECTIVE: The study aimed to compare the effectiveness of a defined formula diet with a blenderized diet on nutritional and respiratory function parameters and to determine the bacteriological load of the two formulations. METHODOLOGY: Seventeen patients, aged 50-75 years, admitted to the University of the Philippines-Philippine General Hospital for chronic bronchitis and/or emphysema, were studied. They were divided into two groups according to dietary regimens. Each group of patients received either the standardized commercial formula or the blenderized formula for 2 weeks. Evaluation of dietary intake, anthropometric measurements, laboratory examinations and lung function were assessed. Subjective evaluation (patient's and physician's assessment) was also sought. Microbiological examinations were performed on the prepared enteral formulas. RESULTS: There was a slight increase in weight and in pulmonary function in both groups but these results did not differ significantly. Possible formula contamination was confirmed. Furthermore, in the overall assessment, the physician and patients rated both formulas as comparable.