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PubMed1994

Early renal effects of occupational exposure to low-level hexavalent chromium.

To detect early renal effects of occupational exposure to hexavalent chromium (Cr), urinary total proteins (U-TP), urinary albumin (U-Alb) and urinary retinol-binding protein (U-RBP) were determined in 166 male Cr platers and 106 male controls. The mean employment time in Cr plating for the platers was 12.6 years. Urinary Cr (U-Cr), which was determined as an index of Cr exposure, ranged from "not detected" to 19.91 micrograms/g creatinine in the platers. The U-Cr level was lower than those in other previous studies. Age-adjusted U-TP, U-Alb or U-RBP levels were not different between the platers and the controls. In the platers, a significant positive correlation was found between age-adjusted U-TP and U-Cr, but U-Cr had no significant relation to age-adjusted U-Alb or U-RBP level. Employment time had no effect on any age-adjusted urinary proteins. The Cr exposure may have been too low to induce definite renal dysfunction. Early renal effects of low-level Cr exposure may be mild, and may not be specific to renal function.

Adolescent↗
PubMed2004

Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats.

Aminoglycoside antibiotics have long been used in antibacterial therapy. Despite their beneficial effects, aminoglycosides have considerable nephrotoxic and ototoxic side effects. It has been reported that reactive oxygen radical species (ROS) play role in the pathophysiology of aminoglycosides-induced nephrotoxicity. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against nephrotoxicity. We investigated the effects of AG on amikacin (AK)-induced changes of renal malondialdehyde (MDA), glutathione (GSH), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) which are used to monitor the development of renal tubular damage. Morphological changes in the kidney were also examined using light microscopy. A total of 21 rats were equally divided into three groups which were: (1) injected with saline, (2) injected with AK, and (3) injected with AK + AG, respectively. AK administration to control rats increased renal MDA and decreased GSH levels. AG administration before AK injection caused significant decreases in MDA and increases in GSH levels in kidneys compared to rats treated with AK alone. The serum BUN level increased slightly, Cr and serum Alb did not change as a result of any treatment. AG tended to decrease the level of serum BUN and did not cause any change in Alb or Cr levels. Morphological changes, including glomerular, tubular epithelial alterations and interstitial edema, were clearly observed in AK-treated rats. In addition, AG reversed the morphological damage to the kidney induced by AK. The results show that AG has a protective effect on nephrotoxicity induced by AK and may therefore improve the therapeutic index of AK.

Amikacin↗
PubMed1998

Population pharmacokinetics of total and unbound etoposide.

A population pharmacokinetics study using the NONMEM program was undertaken to determine the effects of different covariates on the pharmacokinetic parameters of etoposide. A total of 1,044 plasma etoposide concentrations were determined by high-performance liquid chromatography (HPLC) in 100 patients (pts; 75 men and 25 women aged 25-85 years) treated for various tumor types with i.v. (57 pts) or oral (43 pts) etoposide. For 67 pts, etoposide plasma protein binding was determined by equilibrium dialysis; the unbound fraction ranged from 4% to 24%. A linear two-compartment model with first-order absorption (for oral dosing) accurately described the concentration versus time data. The central and peripheral volumes of distribution were significantly correlated with the body surface area [Vc (L) = 5.5 x BSA (m2) and Vp = 4.1 x BSA], but even after BSA had been taken into account, the interindividual variability of the two volumes remained high (34% and 57%, respectively). The clearance (CL) was not correlated with the following covariates: age, BSA, sex, height, and levels of serum bilirubin and liver enzymes. The final regression model for CL was CL (ml/min) = 49.8 x (1 - 0.009 x PRO) x WT/Scr + 33.8 x (1 - 0.29 x META) x (1 - 0.012 x ALB), where ALB, PRO, WT, and Scr, respectively, were albuminemia, proteinemia (g/l), weight (kg), and serum creatinine (microM) and META = 1 if the patient had liver metastases (otherwise, META = 0). The interindividual variability in CL (mean value 30 ml/min) decreased only from 32% to 26% when these covariates were taken into account. The mean oral bioavailability was 66%, showing an interindividual variability of 37%. The plasma clearance of the unbound fraction was strongly and negatively correlated with Scr but was not dependent on either PRO or ALB. These data show that modifications in PRO levels do not directly affect plasma exposure to unbound etoposide. This analysis makes possible the rational consideration of modifications of covariates such as Scr in etoposide dosing. This population data base will constitute the prerequisite for adaptative control with feedback dosing for continuous oral administration of etoposide.

Administration, Oral↗
PubMed2005

Genetic alterations at the Bpag1 locus in dt mice and their impact on transcript expression.

The dystonin/Bpag1 gene encodes several tissue-specific alternatively spliced transcripts that encode cytoskeletal binding proteins. These various isoforms are necessary for maintaining the structural integrity of epithelial, neural, and muscle tissues. Mutations in the dystonin/Bpag1 gene cause dystonia musculorum (dt), a hereditary neuropathy of the mouse characterized by the progressive degeneration of sensory neurons. Several dt mutant alleles exist, most of which have arisen through spontaneous mutations. In this article we demonstrate that the dt locus encodes 107 exons spanning 400 kb. The high frequency of occurrence of spontaneous dt mutants may therefore be a result of the large size of the gene. Analysis of genomic DNA from several dt spontaneous mutant alleles, dt(24J), dt(27J), dt(Alb), and dt(Frk), shows a deletion of the central portion of the gene in dt(Alb) but no large rearrangements or deletions in the other alleles. These other alleles likely have small deletions or rearrangements, or point mutations. To determine the impact of the known and unknown mutations on transcript levels, RT-PCR was performed to detect various coding regions of the dystonin/Bpag1 transcripts in brain and muscle from multiple dt alleles: dt(Tg4), dt(Alb), dt(24J), dt(27J), and dt(Frk). With the exception of dt(Frk), reduced transcript levels were observed for all alleles tested. Such alterations likely result in reduced or absent dystonin/Bpag1 protein levels. Thus, distinct genetic defects lead to a common outcome of reduced transcript expression causing the same phenotype in multiple dt alleles.

Alleles↗
PubMed2005

Isolated blood-cerebrospinal fluid barrier dysfunction: prevalence and associated diseases.

OBJECTIVE: An isolated dysfunction of the blood-CSF barrier is characterised by an abnormal elevation of the albumin CSF/serum concentration ratio (Q(alb)) without any other pathological CSF findings. Although common in routine CSF analysis, the clinical significance of an isolated barrier dysfunction frequently remains unclear. We examined neurological disorders associated with an isolated elevation of Q(alb) to identify possible determinants of blood-CSF barrier dysfunction. METHODS: 367 patients (124 women, 243 men, median age 60. 0 years) out of 3,873 patients receiving diagnostic lumbar puncture at the University Hospital of Ulm (Germany) showed an isolated dysfunction of the blood-CSF barrier. Clinical data as well as MRI findings of these patients were analysed. RESULTS: Isolated barrier dysfunction occurred most frequently (> 30%) in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), normal pressure hydrocephalus (NPH), lumbar spinal stenosis, and polyneuropathy (PNP). In patients who showed no other evidence of neurological disease, isolated barrier dysfunction was found in 14. 9% of cases. The extent of barrier dysfunction was most prominent in brain tumours, GBS, and CIDP. There was a significant correlation of Q(alb) with both weight and body mass index (BMI). CONCLUSIONS: Although isolated barrier dysfunction may be found in a variety of neurological diseases, it is especially frequent in GBS, CIDP, NPH, spinal canal stenosis, and PNP. In these patients, disease-related mechanisms contributing to barrier dysfunction are likely. Moreover, barrier function seems to be influenced by disease-independent determinants like weight and BMI.

Albumins↗
PubMed1998

Effects on the kidney of occupational exposure to styrene.

OBJECTIVES: To elucidate the extent of nephrotoxicity of long-term occupational exposure to styrene. METHODS: In all 10 styrene-exposed workers (employed, mean age 12.6 years) and 15 nonexposed workers were studied. Each participant collected multiple overnight and end-of-shift urine samples. The sum of the urinary concentrations of mandelic acid and phenylglyoxylic acid (MAP) was determined to assess the absorbed dose of styrene. The urinary parameters alanine aminopeptidase (AAP), beta-galactosidase (beta GAL), N-acetyl-beta-D-glucosaminidase (NAG), retinol-binding protein (RBP), and albumin (ALB) were determined to assess the effects on renal function and integrity. RESULTS: The median concentration of MAP in urine was 175 mg/g urinary creatinine (CREAT-U; range 72-496 mg/g). The 8-h time-weighted average (8-h TWA) exposure to styrene was estimated from the urinary concentration of MAP and ranged from 21 to 405 mg/m3. RBP showed a borderline correlation with the dose of styrene. ALB in end-of-shift urine samples showed a borderline correlation with the absorbed dose of styrene. CONCLUSIONS: From the borderline correlation of RBP with the dose of styrene it was concluded that there might be a slight effect on the tubuli. The borderline correlation of ALB with the dose of styrene, together with the observation that five values were above the reference limit of the laboratory, suggests an effect on this parameter.

Acute Kidney Injury↗
PubMed1999

The targeted expression of the human interleukin-2/interferon alpha2b fused gene in alpha-fetoprotein-expressing hepatocellular carcinoma cells.

This study explores the use of a liver-specific albumin promoter and a tumor-specific alpha-fetoprotein (AFP) enhancer to achieve the regulated expression of the cytokine interleukin-2/interferon alpha2b (IL-2/IFNalpha2b) fused gene for treatment of hepatocellular carcinoma (HCC). The human AFP enhancer (E(AFP)) and albumin promoter (P(ALB)) were amplified from human chromosome DNA by the polymerase chain reaction. A recombinant retrovirus was constructed including, as a selectable marker, the neoR gene and the IL-2/IFNalpha2b fused gene controlled by E(AFP)-P(ALB). The liver-targeted expression pattern of the IL-2/IFNalpha2b fused gene was observed when this product was tested in the culture medium of the infected cells (IL-2 activity was 850 IU/10(6) cells, IFNalpha activity was 320 IU/10(6) cells). Moreover, The growth of the IL-2/IFNalpha2b-fused-gene-infected HCC cells, SMMC7721, was clearly suppressed by the second week after innoculation of nude mice compared to the control SMMC7721 cells infected with LXSN and untreated SMMC7721 cells (0.5 +/- 0.1 cm versus 1.4 +/- 0.2 cm and 1.6 +/- 0.2 cm, P < 0.05). The results showed that the combined transcriptional regulatory sequences of E(AFP)-P(ALB) could control the targeted expression of cytokine genes in AFP-positive human HCC cells, and the expression level of the IL-2/IFNalpha2b fused gene was positively correlated to the level of AFP expression in the infected cells. The IL-2/IFNalpha2b fused protein that was expressed has the functions of both IL-2 and IFNalpha. Therefore, this study illustrates the superiority of using transcriptionally targeted recombinant retrovirus vectors in cytokine-based gene therapy.

Albumins↗
PubMed2005

Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells.

With the development of regeneration medicine, many researchers have attempted hepatic differentiation from nonhepatic-origin cell sources. The differentiation of embryonic stem (ES) cells into hepatocyte-like cells has been reported in several papers. Mouse ES cells have shown a potential to develop into hepatocyte-like cells in vitro on the basis of hepatic gene expression after adding several growth factors. We transplanted cultured embryoid body (EB) cells (male) into female mice. A liver specimen of the recipient was examined by immunohistochemical staining for albumin and fluorescence in situ hybridization for the Y chromosome after transplantation. Both Y chromosome- and albumin-positive cells were recognized in the recipient female liver, and were considered to be hepatocyte-like cells derived from ES cells containing the Y chromosome. Many groups, including ourselves, have studied hepatocyte-like cell differentiation from umbilical cord blood cells (UBCs). We cultured nucleated cells isolated from UBCs. Using immunostaining, ALB-positive and CK-19-positive cells were recognized in the culture. Dual staining of ALB and CK-19 demonstrated that ALB was coexpressed with CK-19, suggesting the existence of hepatic progenitors. In this review, we consider recent studies of the differentiation of hepatocytes from nonhepatic origins, especially ES cells and umbilical cord blood.

Animals↗
PubMed2002

Risk factors for infections in cirrhotic patients with and without hepatocellular carcinoma.

BACKGROUND: Patients with liver cirrhosis (LC) frequently have complications with bacterial infections, and these infections increase the mortality rate. However, a detailed analysis of infections associated with LC patients has not yet been performed. METHODS: We analyzed 325 patients with LC with and without hepatocellular carcinoma (HCC) who were hospitalized between 1997 and 1999. RESULTS: Infections developed in 70 (21.5%) patients and 48 (68.6%) of these developed infections during hospitalization. The mortality rate of 28.6% (20/70) in patients with infectious complications was higher than that of 12.5% (32/255) in patients without infectious complications. Forty (57.1%) of the 70 patients had infections of unknown causes; 11 (15.7%) had sepsis; 6 (8.6%) had intravenous hyperalimentation (IVH) infection; 3 (4.3%) each had spontaneous bacterial peritonitis (SBP), liver abscess, and cholecystitis; and 4 (5.7%) had other infections. Bacterial cultures of blood were prepared from 73 of the 325 patients (22.5%), and were positive in 22 of the 73 patients (30.1%). Of these 22 culture-positive patients, 11 had sepsis, 6 had IVH infection, 2 had liver abscess, 1 had cholecystitis, 1 had pneumonia, and 1 had decubitus ulcer. Gram-positive bacterial strains were detected most frequently, in 16 of the 24 strains isolated. Univariate analysis revealed significant differences between the groups with and without infectious complications with regard to hepatitis B virus infection, Child-Pugh classification, ascites, esophageal varices, survival rate, total-bilirubin (T-Bil), albumin (Alb), lactate dehydrogenase (LDH), total cholesterol (T-chol), and prothrombin time (PT). On multivariate analysis, the Alb level was selected as a significant independent factor contributing to the development of infections. CONCLUSIONS: Patients with advanced cirrhosis with low Alb levels should be carefully treated, and the administration of broad spectrum antibiotics covering gram-positive bacteria needs to be considered in the treatment of infections.

Age Distribution↗
PubMed2003

Efficacy of cyclophosphamide combined with prednisolone in patients with AA amyloidosis secondary to rheumatoid arthritis.

Secondary amyloid A (AA) amyloidosis is an uncommon yet important complication of rheumatoid arthritis (RA). It is one of the most relentless of the extra-articular features of RA, and suitable treatments have not yet been found. We studied the efficacy of cyclophosphamide (CYC) combined with prednisolone (PSL) in amyloidotic patients who had serum amyloid A (SAA) 1.3 genotype, which is a risk factor for secondary amyloidosis in Japanese RA patients. Fifteen RA patients who were SAA1.3 homo- and heterozygotes with biopsy-confirmed AA amyloidosis were treated with a combination of CYC and PSL. Laboratory variables of C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), serum albumin (Alb), serum creatinine (Cre) and Lansbury's index were carried out by statistical analysis of changes between before and during the medication. According to the Mann-Whitney rank test, CRP, RF, ESR, Alb and Cre levels improved significantly with the combination treatment (p<0.05). Also, paired t-tests showed significance in Lansbury's index between before and during the medication (p=0.007). CYC combined with PSL ameliorated not only laboratory markers but also clinical rheumatoid activity in patients with amyloidosis secondary to RA, whose genotypes were SAA1.3 homo- and heterozygous. CRP, ESR, RF, Alb and Cre will be surrogate markers of therapeutic efficacy. The combination of CYC and PSL appears to be beneficial for Japanese RA patients who are SAA1.3 homo- and heterozygous carriers, associated with secondary AA amyloidosis.

Aged↗
PubMed1985

Mammalian endoneurial fluid: collection and protein analysis from normal and crushed nerves.

An elution procedure was developed for the extraction of endoneurial fluid from desheathed, rat sciatic nerves. The endoneurial fluid elutions (EFE) from normal and crushed nerves were evaluated for extracellular proteins by sodium dodecyl sulphate-pore gradient electrophoresis (SDS-PGE) after silver stain and after immune overlay following electrophoretic transfer to nitrocellulose using antisera to albumin (ALB), neuron specific enolase (NSE), and the major myelin glycoprotein (P0). After removal of the epineurium/perineurium, the EFE protein accounted for 3.6% (34-37 micrograms) of the total endoneurial protein which did not change with intra-arterial perfusion. The endoneurium was further fractionated to obtain an aqueous supernatant (S-I), an SDS-solubilized supernatant (S-II), and an SDS-insoluble fraction. SDS-PGE analysis revealed that the EFE has a distinctive protein composition relative to the other endoneurial fractions. A predominant band with Mr of 64,600; 4 major bands with Mr of 86,200, 61,000, 54,500 and 46,900; and several other minor bands were observed. The predominant band at 64,600 co-migrates with ALB and was demonstrated by immune overlay to be ALB, which was also the major protein in the S-I fraction. The uniqueness of the EFE was established by the absence of NSE, an enzyme marker for the cytoplasmic fraction of axons which was found to be present only in S-I (subunit Mr = 49,600), the absence of P0, and the distinctive protein profiles as determined by silver stain. Crush injury resulted in a progressive increase in the amount of protein found in the EFE as well as the S-I with a corresponding decrease in S-II protein as a function of time after crush (1, 2, 5, 10, 24, 48, 96, 168 h). Dramatic alterations in the protein profile were demonstrated in the EFE from crushed nerves after SDS-PGE indicating substantial changes in the endoneurium as a result of the axonal degeneration, demyelination, and breakdown of the blood-nerve barrier. Alterations in EFE proteins after crush were also observed by lectin overlay experiments after SDS-PGE. Analysis of EFE collected after crush for NSE and P0 were negative. It is concluded that the distinctive pattern of EFE proteins identified from normal nerve will permit their further characterization as a separate endoneurial protein compartment. Such an elution procedure for collection of endoneurial fluid can readily be adapted to human sural nerve biopsies from patients with peripheral neuropathy for characterization of the appearance of new proteins which may be used as markers of disease activity.

Animals↗
PubMed1990

Developmental changes in blood-nerve transfer of albumin and endoneurial albumin content in rat sciatic nerve.

The rate of entry of albumin into the endoneurial space and its content within that compartment during development were investigated by measuring the permeability coefficient-surface area product to 125I-albumin (PSA) of the blood-nerve interface (BNI), endoneurial residual plasma volume (Vp), blood-nerve interface index to albumin, and endoneurial water content in sciatic nerves of rats ranging in age from 1 to 24 weeks. There was a 30-fold reduction in PSA and a 4-fold decrease in Vp from 2 to 24 weeks, indicating that the endoneurial capillaries and perineurium become less permeable during development. On the other hand, the Alb-BNI index was relatively small at 1 week, increased to a peak value around 6-8 weeks, and then decreased to adult values by 13 weeks. The smaller Alb-BNI index in the neonatal period is consistent with endoneurial albumin being cleared across a permeable perineurium by epineurial lymphatics. Subsequently, as the perineurium becomes less permeable, endoneurial albumin content increases. It then decreases as the endoneurial capillary permeability also decreases. Additionally, metabolic clearance of albumin, especially during the first 2-3 weeks, by axons and glia to meet the nutritive requirements of rapid axonal growth and myelination could be partly responsible for a lower Alb-BNI index. It is suggested that in the developing nerve, the combination of epineurial lymphatics and a relatively permeable perineurium, together with axonal and glial uptake and protein catabolism aid in the clearance of plasma-derived osmolytes from the endoneurial space, and thus prevent the elevation of endoneurial hydrostatic pressure and onset of oedema that would have been seen in an adult nerve with a comparably permeable BNI.

Aging↗
PubMed1992

Identification and purification of a high-affinity thyroxine binding protein that is distinct from albumin and prealbumin in the blood of a turtle, Trachemys scripta.

Fractionation of plasma proteins in the turtle, Trachemys scripta, confirmed the presence of a high-affinity thyroxine (T4) binding protein (TBP) that was distinct from albumin (ALB) and prealbumin (PA). The TBP was isolated by adsorption on a T4-affinity column and a high degree of purification was achieved by gel filtration and preparative electrophoresis. Analysis by reversed-phase HPLC showed a single peak of protein with T4 binding activity. The electrophoretic mobility of the TBP, based on staining and binding to [125I]T4 on nondenaturing polyacrylamide gels (PAGE), corresponded to that of the major T4 binding activity previously identified in plasma (ca. 60 kDa). PA was fractionated as a complex with retinol binding protein (PA-RBP) based on retinol associated fluorescence using ion exchange chromatography on DEAE-Sephacel and gel filtration. This complex behaved as a larger and more highly charged molecule than TBP; it was partially dissociated in low ionic strength basic solution. SDS-PAGE of the PA-RBP-enriched fraction revealed a major component of about 48 kDa (possibly free PA), with smaller components corresponding to those expected for free RBP (ca. 22 kDa) and subunits of PA (e.g., 14 and 28 kDa). ALB was purified by ion exchange chromatography on DEAE and gel filtration; it behaved as less basic than PA with MW approximately 67 kDa. TBP accounted for virtually all the T4 binding activity of whole plasma: TBP was about 100 times as active and PA and ALB were less than 1% as active as plasma. The binding affinity of purified TBP was similar to that of whole plasma from turtle and human (e.g., approx. 10(9) M-1 on Sephadex G-25).

Animals↗
PubMed1976

Polyacrylamide-gel disc electrophoresis of native cerebrospinal fluid proteins with special reference to immunoglobulins and some clinical applications.

Polyacrylamide-gel disc electrophoresis has been applied to the fractionation of CSF samples obtained from 2m control subjects (range of age 16 to 77 yr, mean 41.0 yr) and from 157 patients with various neurological diseases, with the purpose of evaluating the diagnostic significance of separated protein bands. It was found that the immunoglobulins, with some exceptions, were fractionated in the G-zone which was defined as an area between the origin and 0.57 in terms of relative migration based on transferrin (RT). Fourty-four percent of the whole Bence Jones protein bands which were examined were detected in the area of RT 0.70-0.90. The normal values of CSF protein fractions were (means+/-SD):Pre-alb-zone, 10.97+/-2.31%; Alb-zone, 40.74+/-5.72%; A1-zone, 5.25+/-0.72%; A2-zone, 8.23+/-1.24%; B1-zone, 10.82+/-2.18%. B2-zone, 7.94+/-1.93%; G-zone, 16.05+/-2.49%. The following significant results were obtained: (1) When the total protein concentration (TP) of CSF is increased: the percentage of the Pre-alb-zone is lowered and that of the A1- and G-zones is increased in diseases such as neurosyphilis, infectious meningitis, brain tumour, multiple sclerosis, intervertebral disc protrusion and cerebral infarction. The A2-zone was diminished in cerebral infarction, and a similar change was seen in brain tumour with in addition a decrease of the B2-zone; (2) When the TP was normal: the percentage of the G-zone was increased in multiple sclerosis, brain tumour and intervertebral disc protrusion. In the latter 2 disorders the A1-zone also increased. This fraction also increased in the cases of cerebral infarction, whose mean age was, however, much higher than that of the control subjects.

Adolescent↗
PubMed1989

The pathophysiology of rhinitis. III. The control of IgG secretion.

To examine the sources of IgG in nasal secretions, nasal provocation tests with histamine (H) and methacholine (MC) were performed on 22 subjects. Nasal lavages were assayed for IgG, total protein, albumin (Alb), nonsecretory IgA (nonsIgA), and secretory IgA (sIgA). H stimulation dramatically increased the secretion of IgG, nonsIgA, and Alb and also increased the proportion of these proteins compared to total protein. H-induced protein secretion was significantly inhibited by nasal pretreatment with chlorpheniramine maleate but was unaffected by atropine sulfate. sIgA was also stimulated by H challenge, but unlike IgG and other vascular proteins, the proportion of sIgA to total protein (sIgA percent) decreased after H challenges. MC stimulation also increased secretion of IgG, Alb, nonsIgA, and sIgA but did not alter their proportions, compared to total protein. Topical atropine significantly inhibited secretion of all proteins, suggesting a mode of transportation mediated by glandular muscarinic receptor stimulation. Thus, MC can increase the amount of IgG secretion, whereas H increases both the amount and relative proportion of IgG in nasal secretions. These data suggest that pharmacologic stimulation of IgG into nasal secretions may be used as a total to modulate mucosal immunity.

Administration, Topical↗
PubMed1995

Heart failure in Nigerian hypertensive patients: the role of renal dysfunction.

Heart failure in hypertensive patients is known to be dependent not only on the absolute value of blood pressure but also on other factors, hence the prognosis varies. In this study, the effect of renal dysfunction on the development of heart failure in hypertensive patients was assessed. Fifty-five patients who were admitted in hypertensive heart failure (HHF) were compared with 55 hypertensive patients who had never been in heart failure (HT), in their renal function, assessed by serum creatinine and urea levels. The haemoglobin (Hb) and serum albumin (Alb) levels were also measured. The two groups were matched for age, sex, level of blood pressure and body mass index. The duration of hypertension was similar in both groups. Mean serum creatinine was higher in the HHF group: 4.50 +/- 0.90 vs. 0.97 +/- 0.06 mg/100ml (P < 0.001). Also the Hb and Alb levels were lower in the HHF than the HT group: 11.63 +/- 0.40 vs. 13.2 +/- 0.21 g/100 ml (P < 0.001) and 3.7 +/- 0.1 vs. 4.40 +/- 0.09 g/100 ml (P < 0.001), respectively. The proportion with abnormal renal function (creatinine > 1.5 mg%) was also significantly higher in HHF: 28/55 vs. 8/54, chi 2 = 16.3 (P < 0.001). When adjustment was made for low serum albumin, Hb and fundal changes by multivariate analysis, serum creatinine was significantly higher in the HHF group: F = 4.294 (P < 0.05). Low serum albumin was also independent of haemoglobin and creatinine: F = 19.52 (P < 0.001), but Hb was not significantly different after adjustment for Alb and creatinine. This study suggests that renal dysfunction is independently associated with the development of heart failure in HT patients.

Analysis of Variance↗
PubMed1994

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit.

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

Journal Article↗
PubMed1986

The lymphatic route--II. Pharmacokinetics of human recombinant interferon-alpha 2 injected with albumin as a retarder in rabbits.

The aim of the present investigation was to define whether multisite subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human recombinant interferon-alpha 2 (rec. IFN-alpha 2) either in saline, human albumin (ALB) solution (4, 7 and 10% final concentrations), or in a solution containing 75 U of hyaluronidase, modified the pharmacokinetic parameters calculated from the IFN plasma levels. Plasma disappearance rates of rec. IFN-alpha 2 were measured in rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a three-pools mammillary model. This model was the basis for evaluating the absorption and distribution of rec. IFN-alpha 2 after s.c. administration. The increase of ALB concentration (from 4 to 10%) caused a significant reduction of the plasma IFN Cmax while both the mean residence time and the release time of IFN increased linearly with the ALB concentration. The data support the postulation that s.c. administration of albumin acts as an interstitial fluid expander and may favour absorption of IFN via lymphatics rather than blood capillaries. Improvement of therapeutic index of IFN by using this route remains to be shown in clinical trials.

Animals↗