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Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood-cerebrospinal fluid barrier dysfunction.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized pathogenic particle in human plasma, but its presence in the cerebrospinal fluid and its possible role in the central nervous system have not been documented. We tested the hypothesis that apolipoprotein(a) [apo(a)], free or as a component of the Lp(a) particle, can cross the blood-cerebrospinal fluid barrier and be found in the cerebrospinal fluid of patients affected by neurologic pathologies. METHODS: We studied paired cerebrospinal fluid/serum samples from 77 patients with inflammatory (n=20) or noninflammatory (n=34) blood-cerebrospinal fluid barrier dysfunction and without blood-cerebrospinal fluid barrier dysfunction (n=23). We used ELISA to measure Lp(a) concentrations and Western blot and immunodetection to analyze apo(a) isoforms in native and reducing conditions. RESULTS: Entire Lp(a) with either small or large apo(a) isoforms was present in the cerebrospinal fluid of patients with blood-cerebrospinal fluid barrier dysfunction, regardless of its pathogenesis. Multiple linear regression analysis showed that both serum Lp(a) concentration (P=0.003) and cerebrospinal fluid/serum albumin ratio (P<0.001) were predictors of the Lp(a) concentration in cerebrospinal fluid. CONCLUSIONS: Our results demonstrate that Lp(a) can cross a dysfunctional blood-cerebrospinal fluid barrier. The unusual presence of Lp(a) in the cerebrospinal fluid could extend some of its known pathogenic effects to the central nervous system.

Adolescent↗

Extracellular 70-kd heat shock protein in mid-trimester amniotic fluid and its effect on cytokine production by ex vivo-cultured amniotic fluid cells.

OBJECTIVE: The 70-kd heat shock protein is released from cells in response to stress and functions as a regulator of innate immunity. We hypothesized that 70-kd heat shock protein in mid-trimester amniotic fluid might regulate local immune system activation. STUDY DESIGN: Amniotic fluid that was obtained from 200 women who underwent amniocentesis at 15 to 19 weeks of gestation was tested by enzyme-linked immunosorbent assay for 70-kd heat shock protein, tumor necrosis factor-alpha, and interleukin-1beta and -6. The amniotic fluid cellular fraction also was evaluated for Mycoplasma hominis by gene amplification. Whole amniotic fluids were incubated ex vivo in medium alone or medium that contained peptidoglycan, a TLR2 ligand, or lipopolysaccharide, a TLR4 ligand. After 24 hours, the supernatants were collected and assayed for 70-kd heat shock protein. The influence of exogenous 70-kd heat shock protein on tumor necrosis factor-alpha and interleukin-1beta and -6 production by whole amniotic fluid was assessed similarly. RESULTS: The 70-kd heat shock protein was detected in all amniotic fluids with a median (range) of 11.5 ng/mL (1.2-76.7). The intra-amniotic 70-kd heat shock protein concentration was correlated positively only with amniotic fluid tumor necrosis factor-alpha levels (P = .0002). Detection of M hominis was associated with an increased 70-kd heat shock protein concentration (median, 17.2 ng/mL; P = .01). The addition of peptidoglycan resulted in a stimulation of 70-kd heat shock protein production, and exogenous 70-kd heat shock protein stimulated the release of tumor necrosis factor-alpha by amniotic fluid cells. CONCLUSION: The 70-kd heat shock protein is released from cells in mid-trimester amniotic fluid as a consequence of TLR2 stimulation and potentiates tumor necrosis factor-alpha production.

Amniotic Fluid↗

Randomized trial of two levels of fluid input in the perinatal period--effect on fluid balance, electrolyte and metabolic disturbances in ventilated VLBW infants.

The aim of this study was to determine whether fluid restriction does indeed significantly increase acute adverse effects. One-hundred-and-sixty-eight ventilated infants, median gestational age 27 wk (range 23-33) and birthweight 953 g (range 486-1500), entered into a randomized controlled trial of two fluid regimes. Infants on regime A were to be prescribed 60 ml/kg of fluids on day 1 which was gradually increased over the first week to 150 ml/kg, infants on fluid regime B were to be prescribed approximately 20% less fluid over the first week. Daily fluid input and output were recorded. Serum electrolytes, bilirubin, creatinine and urine osmolalities were measured daily. Arginine vasopressin levels were assessed on days 1, 3 and 5. Episodes of jaundice, hypoglycaemia and hypotension requiring treatment were noted. Infants on regime B actually received overall 11% and, in the first 4 days, 19% less fluid than those on regime A (p < 0.001). There were no statistically significant differences in the occurrence of episodes of jaundice, hypotension, hypoglycaemia, hypernatraemia or hyponatraemia between infants on the two regimes. Although the infants on regime B had significantly higher urine osmolalities and lower urine output for most of the perinatal period, their median creatinine and arginine vasopressin levels did not differ significantly from those on regime A. We conclude that fluid restriction to less than 90% of usual maintenance fluids is not associated with an excess of acute adverse effects.

Dehydration↗

Fluid administration, brain edema, and cerebrospinal fluid lactate and glucose concentrations in experimental Escherichia coli meningitis.

The effect of no fluids versus liberal fluid supplementation on brain edema and cerebrospinal fluid (CSF) lactate and glucose concentrations was compared in rabbits with experimental Escherichia coli meningitis. Fluid restriction for the duration of the experiment (19 h) led to a decrease in body weight by approximately 5%, while the high fluid regimen increased body weight by approximately 5%. Infected animals developed brain edema compared with controls, but the fluid regimen had no measurable effect on the degree of edema. In contrast, fluid-restricted animals had significantly higher CSF lactate and lower CSF glucose concentrations than fluid-supplemented animals (lactate, 13.5 +/- 3.5 vs. 10.1 +/- 3.3 mmol/L; glucose, 1.89 +/- 1.39 vs. 4.11 +/- 1.39 mmol/L). These results fail to support the hypothesis that administration of large amounts of fluid in this model of gram-negative bacterial meningitis aggravates brain edema.

Animals↗

Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women.

Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged.

Adult↗

Critical steps in electronic volume quantification of gingival crevicular fluid: the potential impact of evaporation, fluid retention, local conditions and repeated measurements.

BACKGROUND AND OBJECTIVES: Various methodological factors may operate during clinical gingival crevicular fluid (GCF) sampling, volume quantification or subsequent laboratory analysis. For precise volume quantification, specific concern for generation and maintenance of a reliable calibration curve, the potential risk of GCF loss as a result of evaporation or fluid retention on actual volume and the impact of local conditions is needed because each of these factors may act as a source of subsequent volumetric distortions. Thus, the present study aimed to analyse the impact of sample transfer time on the rate of evaporation and the possibility of fluid retention, and the impact of local conditions and number of replicated measurements on the reliability of calibration data. MATERIALS AND METHODS: To analyse evaporative errors, standardized Periopaper strips provided with known test volumes (0.1 microl, 0.2 microl, 0.5 microl and 0.6 microl) were transferred to Periotron 8000 with different time intervals (immediately, 5 s, 30 s and 60 s). For fluid retention, after quantifying the actual volume of the strips provided with known volumes (0.1 microl and 0.6 microl) of two test fluids, a second set of measurements was performed using dry strips. To determine the impact of local conditions (temperature and humidity) and the validity of 3, 5 and 20 replications (0.0-0.6 microl with 0.1- microl increments) on device calibration for 20 degrees C and 25 degrees C, electronic readings were obtained from three devices at three different locations. Differences in volumetric data in each experimental design were statistically analysed. RESULTS: No significant fluid loss was observed within 5 s, but evaporation clearly led to volumetric distortions with extending transfer times (30 s or 60 s) (p < 0.05). Measurable amounts of fluid retention were found for both volumes and both test fluids, but not with identical patterns. Local conditions resulted in unique calibration data for each test volume and for each device. Although a 5 degrees C increase generally provided higher readings, this was not observed for all devices at all volumes. Additional replicates (n = 5 or n = 20) did not seem to add any further reliability to the triplicate scores for the given test volumes. CONCLUSION: The findings of the present study confirm the reliability of triplicate readings, and uniqueness of each device and electronic data and the distinct impact of local environmental conditions on the generation/maintenance of calibration scores for each particular device. Furthermore, they underline time-dependent evaporation and fluid retention as additional technical concerns and once again highlight the importance of methodological standardization of the electronic volume quantification process.

Calibration↗

Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial.

A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinal fluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used.

Child↗

Correction of gamma-glutamyl transpeptidase deficiency in amniotic fluid of some cystic fibrosis fetuses by mixing with nondeficient fluids.

The deficiency of gamma-glutamyl transpeptidase activity, which was evident in some but not all cystic fibrosis amniotic fluids, could be corrected by mixing with either normal fluids or nondeficient cystic fibrosis fluids. Incubation of any amniotic fluid for 20 min at 62 degrees C resulted in total loss of gamma-glutamyl transpeptidase activity, but the activity could be restored by mixing with untreated nondeficient fluids. In contrast, no restoration could be obtained by mixing with untreated deficient cystic fibrosis fluids. Dialysis of amniotic fluids did not diminish their corrective capacity. Only the transpeptidation reaction was corrected and no correction was observed for the hydrolysis or autotranspeptidation of gamma-glutamyl p-nitroanilide in the absence of the glycylglycine or methionine acceptor. Plasma specimens did not have any corrective activity, although their gamma-glutamyl transpeptidase activity could be restored after heat inactivation by mixing with untreated nondeficient amniotic fluids. No correction was found for aminopeptidase or disaccharidase activities. These findings suggest that the deficient cystic fibrosis amniotic fluids probably contain normal quantities of the gamma-glutamyl transpeptidase enzyme but lack a heat-labile nondialyzable activator that is necessary for its transpeptidation catalytic performance. An assay for this transpeptidase activator may provide a valuable approach to identify at least a subgroup of cystic fibrosis patients.

Aminopeptidases↗

Variability of hydrostatic hepatic vein and ascitic fluid pressure, and of plasma and ascitic fluid colloid osmotic pressure in patients with liver cirrhosis.

The variability of hydrostatic hepatic vein and ascitic fluid pressures and of plasma and ascitic fluid colloid osmotic (oncotic) pressures was assessed during hepatic venous catheterization by repeated measurements on different days and at different locations in patients with cirrhosis of the liver. Furthermore, calculation of oncotic pressure from protein determinations was compared to the directly measured value of plasma and ascitic fluid samples. Repeated measurements of hydrostatic pressure in the same hepatic vein within 15 min showed a standard deviation (SD) below 1 mmHg. The variation in hydrostatic hepatic vein pressures, pressure differences and ascitic fluid pressures (when measured at different locations within the liver and peritoneal space during a single examination) was 1.5, 1.0 and 1.0 mmHg (SD), respectively. When measured on different days, the variation of hydrostatic hepatic vein pressures, pressure differences and ascitic fluid pressures was 2.5, 1.6 and 1.3 mmHg (SD), respectively. Repeated measurements of oncotic pressure on the same plasma sample varied 0.3 and 0.6 mmHg (SD) when measured on the same day and a subsequent day, respectively. The variation in plasma and ascitic fluid oncotic pressure, when measured on samples obtained on different days, was 2.0 and 0.6 mmHg, respectively. The error of oncotic pressure calculated from protein determinations was 2.9 and 1.3 mmHg (SD) for plasma and ascitic fluid, respectively. It is concluded that measurements during catheterization give a good reproducibility in determination of the hydrostatic pressures in hepatic vein and ascitic fluid and of the colloid osmotic (oncotic) pressure in plasma and ascitic fluid in the resting supine patient with cirrhosis, which substantiates the use of measurements during a short period as representative for the patients long-time level.

Ascitic Fluid↗

Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery.

OBJECTIVE: To evaluate the relationship between interleukin (IL)-18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra-amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term. DESIGN: A prospective follow up study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. SAMPLE: Women with singleton pregnancies (<34 weeks) presenting with preterm labour (n = 87) or preterm prelabour rupture of membranes (n = 47) and women, not in labour, at term (n = 28). METHODS: Amniotic fluid was retrieved transabdominally. Cervical mucus was taken from the uterine cervix of women in preterm labour and at term. IL-18 was analysed with enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: IL-18 in relation to microbial invasion of the amniotic fluid, delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. RESULTS: The levels of IL-18 in cervical mucus and amniotic fluid were higher in women with preterm labour than in those not in labour at term. In the preterm labour group, significant associations were found between elevated IL-18 in amniotic fluid and microbial invasion of the amniotic fluid, as well as between delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. Delivery was delayed longer in the preterm prelabour rupture of membranes subgroup with IL-18 >or=1.0 ng/mL than in that with IL-18 <1.0 ng/mL. CONCLUSIONS: In the preterm labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated with microbial invasion of the amniotic fluid, intra-amniotic inflammation and prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture of the membranes group correlated with a longer interval to delivery.

Adult↗

Cerebrospinal fluid dynamics and cerebrospinal fluid infusion in children. Part II: Clinical application of lumbar cerebrospinal fluid infusion in children with macrocephaly and normal growth rate of the head circumference.

In fourteen children with macrocephaly and a normal growth rate of the head circumference, the CSF dynamics were studied by means of the lumbar CSF infusion test with constant flow. We discuss the significance of the outflow resistance together with the advantage of the Pressure Volume Index, which constitute the major parameters of the test. On the basis of computed tomography, we were able to show a differentiation in macrocephaly between megalencephaly, so-called external ventricular obstructive hydrocephalus and communicating hydrocephalus. We were not able to establish a disturbance of the CSF dynamics in megalencephaly and external ventricular obstructive hydrocephalus. In communicating hydrocephalus, CSF absorption was normal, whilst the Pressure Volume Index was elevated. As far as we have been able to ascertain, we are the first in the field to point to a positive correlation between ventricular size and Pressure Volume Index in children with moderately enlarged CSF-spaces.

Adolescent↗

Tissue fluid pressure, lymph pressure, and fluid transport in rat intestinal villi.

Tissue fluid pressure (Pt) and lymph pressure (Pl) as well as fluid transport between initial lymphatics and tissue matrix were determined in the villi of the jejunum in vivo and in vitro. When the intestine was absorbing fluid, free tissue fluid as a micro pool appeared in the villi. Pt and Pl were 2.4 +/- 0.7 and 2.9 +/- 0.8 mm Hg (mean +/- SE), respectively, in the villi in vivo (26 villi of 5 rats) or 0.8 +/- 0.4 and 1.2 +/- 0.5 mm Hg, respectively, in the villi in vitro (30 villi of 5 rats). Pl was significantly (P less than 0.01) higher than Pt. When Evans blue in saline was continuously infused into an initial lymphatic, dye rapidly leaked out into the tissue matrix, but when it was infused into the free tissue fluid, dye did not enter the lymphatics but leaked out of the epithelial layer, apparently due to low hydraulic conductance of the tissue matrix to fluid transport in this direction. Furthermore, in the villi with fat absorption, a retrograde flow of chylous lymph out of the villous tips always occurred, indicating that there are large pores at the villous tips to allow free passage of fluid and chylomicrons. From these findings and other evidences, it is inferred that during fluid absorption a fraction of the lymph may be formed by the transport of the luminal fluid directly into the terminal end of the initial lymphatics via large pores at the villous tips presumably by inhibition of the tissue matrix or by lymphatic suction or both.

Animals↗

Changes in the perceived pleasantness of fluids before and after fluid loss through exercise: a demonstration of the association between perceived pleasantness and physiological usefulness in everyday life.

It has previously been suggested that the perceived pleasantness of a food item in any situation may be directly related to the physiological usefulness of that item to the consumer in that situation. This study investigated changes in the perceived pleasantness of fluids before and after fluid loss through exercise-an everyday situation in which physiological need can alter. Total of 40 exercisers achieving high fluid loss (Group H) and 41 exercisers achieving low fluid loss (Group L) rated seven fluids of varying osmolality, electrolyte content, and energy content on measures of pleasantness, before and after exercise. After fluid loss compared to before fluid loss, perceived pleasantness of all fluids increased (F(1,79)=14.58, p<0.01), and effects were greater in Group H compared to Group L (F(1,79)=8.29, p<0.01). Perceived pleasantness was also significantly higher for fluids of lowest osmolality (F(6,474)=2.14, p<0.05), and effects were again greater in Group H compared to Group L (F(6,474)=2.10, p<0.05). Both findings suggest that perceived pleasantness is related to physiological usefulness, and can be demonstrated in everyday situations.

Beverages↗