Corroboration of normal and abnormal fetal cerebral lamination on postmortem MR imaging with postmortem examination.

BACKGROUND AND PURPOSE: The presence of normal fetal cerebral lamination of the germinal matrix, intermediate zone, subplate layer, and cortex can be used as a marker of normal fetal cerebral development. Our aim was to compare postmortem MR imaging assessment of normal and abnormal fetal cerebral lamination on T1- and T2-weighted images with histopathology. MATERIALS AND METHODS: Fifty-five formalin-fixed brains from postmortem fetuses, ranging from 16 to 30 weeks' gestational age, mean of 23 weeks, underwent T1- and T2- weighted MR imaging and subsequent sectioning and histologic examination. The cerebral lamination was graded as normal or abnormal on T1- and T2-weighted imaging and compared with postmortem findings. The sensitivity, specificity, and positive and negative predictive values of T1 and T2 assessment of cerebral lamination were calculated. RESULTS: Twenty-six fetuses had abnormal and 29 had normal cerebral lamination on histology. On T1, the overall sensitivity, specificity, and positive and negative predictive values of evaluating cerebral lamination were 96.15%(CI, 78.42%-99.80%), 89.66%(CI, 71.50%-97.29%), 89.29%(CI, 70.63%-97.19%), and 96.29%(CI, 79.11%-99.80%), respectively. On T2, the overall sensitivity, specificity, and positive and negative predictive values of evaluating cerebral lamination were 73.08%(CI, 51.95%-87.65%), 96.55%(CI, 80.37%-99.82%), 95.00%(CI, 73.06%-99.74%), and 80.00%(CI, 62.54%-90.94%), respectively. CONCLUSIONS: Postmortem MR imaging has high sensitivity, specificity, and positive and negative predictive values in assessing fetal cerebral lamination compared with histology. T1-weighted imaging has a higher sensitivity and negative predictive value, while T2-weighted imaging has a higher specificity and positive predictive value.

Alteration of human fetal subplate layer and intermediate zone during normal development on MR and diffusion tensor imaging.

BACKGROUND AND PURPOSE: The subplate layer and intermediate zone are the precursors for neonatal white matter. The aims of this study were to evaluate 1) T1 and T2 signal intensity, and 2) FA of subplate and intermediate zone in postmortem fetuses and correlate with histology, and 3) T2 signal intensity of subplate and intermediate zone on antenatal MR imaging. MATERIALS AND METHODS: Fourteen immersion-fixed normal brains from 18 to 25 gestational weeks underwent 1.5T MR imaging, including DTI and histologic examination. The subplate and intermediate zone were graded on a scale of 1-5 on T1 and T2, and FAs were evaluated and then correlated with age. Seventeen antenatal MR images from 20 to 26 gestational weeks with normal brain were evaluated by using the same grading. RESULTS: On T1 postmortem MR imaging, subplate has lower signal intensity compared with intermediate zone; subplate signal intensity correlated positively (r = 0.66, P = .012) with age, and intermediate zone signal intensity correlated negatively (r = -0.78, P = .001) with age. On T2 postmortem MR imaging, subplate has higher signal intensity compared with intermediate zone and remained persistently high in signal intensity; intermediate zone signal intensity showed moderate correlation (r = 0.48, P = .086) with age. FA of subplate correlated positively (r = 0.55, P < .001) with age; FA of intermediate zone correlated negatively (r = -0.64, P < .0001) with age. On histology, extracellular matrix decreased and cellularity increased in subplate layer, tangentially organized cellularity decreased, and projecting fibers became thicker in intermediate zone with increasing gestation. The findings on T2-weighted antenatal MR imaging were similar to T2-weighted postmortem MR imaging. CONCLUSIONS: The changes in signal intensity and FA of subplate and intermediate zone in the second trimester reflect microstructural changes on histology.

Ruminal and blood responses to propylene glycol during frequent feeding.

The objective of the current experiment was to study the responses of ruminal and blood metabolites of Holstein dairy cows to propylene glycol (PG) under different methods of delivery during frequent feeding. By providing the same amount (200 mL or 200 g) of PG, delivery methods for PG were assessed: 1) control treatment: no PG; 2) dietary treatment: 200 g of PG as a dry product (65% purity; corresponded to 308 g of the dry product) mixed into the TMR; 3) oral-drench treatment: 200 mL of liquid PG (100% purity) orally drenched; and 4) rumen-drench treatment: 200 g of PG as a dry product drenched via the rumen cannula to mimic top dressing. Eight multiparous (lactation = 3 +/- 1.1 SD) ruminally cannulated Holstein dairy cows (DIM = 204 +/- 104.5 SD) were fed PG for 4 d (d 11 to 14) in a replicated 4 x 4 Latin square design with an experimental length of 14 d for each period. On the last day of each period, serial blood samples were removed from an indwelling catheter placed in the right jugular vein immediately before and for 4 h after PG administration. Cows were fed at 12x feeding/d for 2 d before entering the serial sampling period to minimize postprandial influences on blood metabolites. Ruminal content was also sampled hourly for 4 h on d 14. Milk was sampled from 2 consecutive milkings on d 13 during each period. Dry matter intake and milk yield were not affected by PG. Percentages of milk lactose were increased by PG delivered by all methods tested in the current experiment. Ruminal concentrations (as percentages of total volatile fatty acids) of acetate were decreased and concentrations of propionate and isovalerate were increased by PG, regardless of the delivery method; however, total volatile fatty acid concentration was not affected by PG. Ruminal concentrations of butyrate were decreased and concentrations of valerate were increased by PG drench, via either an oral or ruminal drench. The degree of reduction in butyrate concentration or increase in valerate concentration was affected by PG dose. Serum insulin peaked more rapidly and at a greater concentration for cows receiving PG via drenching, but not when PG was provided as a part of the TMR. Plasma glucose, however, tended to peak more rapidly at a greater concentration for cows receiving PG, regardless of the delivery method. Propylene glycol for the amount drenched (orally or ruminally) or fed (incorporated into the ration) shifted ruminal fermentation toward a more glucogenic environment. Drenching demonstrated a better efficacy than feeding PG because of the amount of PG that was available to the animal at the time of sampling. Effects of drenching dry PG into the rumen were comparable with orally drenching liquid PG.

Effects of rumen-protected choline and dry propylene glycol on feed intake and blood parameters for Holstein dairy cows in early lactation.

A 6 x 6 Latin square design was used to test 3 sets of comparisons simultaneously to study response in dry matter intake, milk yield, and blood parameters to propylene glycol (PG) supplementation delivered by 2 methods [incorporating PG into the total mixed ration (TMR) vs. top dressing; comparison I]; individual or combined dietary choline and PG supplementation as a 2 x 2 factorial (comparison II); or increasing amounts of dietary choline (comparison III). Six multiparous (lactation number = 1.5 +/- 0.8 SD) Holstein dairy cows were at 41 d in milk (+/- 9 SD) at the start of the experiment. Propylene glycol used was a dry product containing 65% PG, and choline was a rumen-protected choline product (RPC; estimated to be 50% rumen-protected) containing 50% choline chloride. In comparison I, treatments compared were 1) control: no PG; 2) PG-TMR: 250 g/d of dry PG (corresponding to 162.5 g/d of PG) incorporated into the TMR; and 3) PG-top dress: 250 g/d of dry PG top-dressed onto the TMR. In comparison II, treatments compared were 1) control: no PG and no RPC; 2) PG: 250 g/d of dry PG incorporated into the TMR; 3) RPC: 50 g/d of RPC top-dressed onto the TMR; and 4) PG+RPC: combination of treatments 2 and 3. In comparison III, treatments compared were 0, 25, and 50 g/d of RPC top-dressed onto the TMR. Each experimental period lasted 10 d with 9 d of adaptation followed by 1 d of serial blood sampling. Dry matter intake and milk yield were recorded daily. During the serial blood sampling, jugular blood was sampled every 20 min for the first 4 h and at 8 and 12 h after treatment administration. Results obtained from comparison I showed that feeding 250 g/d of PG as a dry product decreased plasma beta-hydroxybutyrate (BHBA) concentration (mean +/- SEM) from 701 +/- 81 (control) to 564 +/- 76 micromol/L without affecting serum insulin, plasma glucose, or plasma nonesterified fatty acid concentrations. Top-dressing PG decreased plasma BHBA concentrations more than by incorporating it into the TMR [527 vs. 601 micromol/L (+/- 81 pooled SEM)]. Results obtained from comparison II showed that supplementing choline as RPC, PG, or both had no effect on dry matter intake, milk yield, or any of the blood parameters measured. Results obtained from comparison III showed that milk yield tended to increase linearly with increasing amounts of dietary choline as RPC. We concluded that feeding PG as a dry product reduced plasma BHBA concentration but top-dressing PG was more efficient at reducing plasma BHBA level than incorporating PG into the TMR. Dietary choline as RPC tended to increase milk yield linearly. However, a combined effect of dietary PG and choline was not evident and therefore not beneficial.

Diagnosis and management of spontaneous cerebrospinal fluid-middle ear effusion and otorrhea.

OBJECTIVES/HYPOTHESIS: Spontaneous leak of cerebrospinal fluid (CSF) into the middle ear can occur in adults without a history of temporal bone trauma or fracture, meningitis, or any obvious cause. Therefore, clues may be lacking that would alert the otolaryngologist that fluid medial to an intact eardrum, or fluid emanating from an eardrum perforation, is likely to be CSF fluid. A review of relevant medical literature reveals that herniation of the arachnoid membrane through a tegmen defect may be congenital, or CSF leak may occur when dynamic factors (i.e., brain pulsations or increases in intracranial pressure) produce a rent in the arachnoid membrane. Because tegmen defects may be multiple rather than single, identifying only one defect may not be sufficient for achieving definitive repair. Data on nine cases of spontaneous CSF leak to the ear in adult patients from four medical centers are presented and analyzed to provide collective information about a disorder that can be difficult to diagnose and manage. STUDY DESIGN: Retrospective review of nine cases of spontaneous CSF middle ear effusion/otorrhea. RESULTS: The majority of patients presented with symptoms of aural fullness and middle ear effusion. Many developed suspicious clear otorrhea only after insertion of a tympanostomy tube. Two patients had multiple defects in the tegmen and dura, and five patients had meningoencephaloceles confirmed intraoperatively. Five patients underwent combined middle cranial fossa/transmastoid repair. Materials used in repair included temporalis fascia, free muscle graft, Oxycel cotton, calvarial bone, pericranium, bone wax, and fibrin glue. CONCLUSIONS: CSF middle ear effusion/otorrhea can develop in adults without a prior history of meningitis or head trauma or any apparent proximate cause. Although presenting symptoms can be subtle, early suspicion and confirmatory imaging aid in establishing the diagnosis. Because surgical repair by way of a mastoid approach alone can be inadequate if there are multiple tegmen defects, a middle fossa approach alone, or in combination with a transmastoid approach, should be considered in most cases.

Health-related quality of life for adults with cystic fibrosis: a regression approach to assessing the impact of recombinant human DNase.

STUDY OBJECTIVES: To examine the general health-related quality of life (HRQOL) of adults with cystic fibrosis (CF) using available generic instruments, and to determine important predictors of change in HRQOL, including therapy with recombinant human Dnase (rhDNase). DESIGN: Prospective, observational study. PATIENTS: Fifty-nine adults with CE. INTERVENTION: The Medical Outcomes Study Short-Form 36 (SF-36) and the EuroQol (EQ-5D) were mailed to patients; follow-up surveys were mailed 1 year later. MEASUREMENTS AND MAIN RESULTS: Multivariate regression analyses assessed the relationships between clinical and demographic variables and change in health status. The 39 respondents reported lower HRQOL scores compared with general population norms for generic instruments. Regression analyses indicated that age (p=0.010), percentage predicted forced expiratory volume in 1 second (p=0.005), hospital admission (p=0.023), and rhDNase therapy (p=0.026) were positively associated 1998 EQ-5D index scores, whereas body mass index was negatively associated (p=0.025) with 1998 EQ-5D index scores after controlling for baseline 1997 scores. The size of the regression coefficients indicated that only 1997 scores and hospital admission in the year were quantitatively importantly associated with 1998 scores. Baseline HRQOL assessments showed that adults with CF reported important decrements in health status and functioning. An interesting relationship between functional status and total household income was observed. CONCLUSION: Although a statistically significant association between rhDNase and 1-year change in HRQOL was found on multivariate regression analysis, the magnitude of this relationship may not be clinically important.

Cost of care for individuals with cystic fibrosis: a regression approach to determining the impact of recombinant human DNase.

We estimated direct medical costs of care and important determinants of the costs in patients with cystic fibrosis (CF), including therapy with recombinant human DNase (rhDNase). Costs were estimated with resource use data from the Epidemiologic Study of Cystic Fibrosis. Ordinary least squares regression was used to determine the effect of clinical and demographic variables on individual cost of care. The estimated cost of caring for 303 patients in Alberta was $2,279,801 in 1996. The mean cost of care was $7524 (range $386-92,376)/patient. Regression results indicated that age and forced expiratory volume predicted had a negative association with costs. Being female, receiving rhDNase, and having Pseudomonas aeruginosa or Burkholderia cepacia were all associated with high costs. Our estimates indicated large interindividual variation in cost of care for patients with CF.

Functional characterization of two Ultraspiracle forms (CtUSP-1 and CtUSP-2) from Chironomus tentans.

Two forms, CtUSP-1 and CtUSP-2, of the Chironomus tentans homolog of Ultraspiracle (new nomenclature: Chironomus NR2B4) were described and verified as components of the functional ecdysteroid receptor. The two forms differed from each other in the most N-terminal regions of the A/B domain and were tested for several properties. Both forms showed the ability to heterodimerize with CtEcR and interact with a variety of direct repeat and palindromic EcREs, and both conferred specific ligand binding when heterodimerized with EcR. CtUSP-2 showed a twofold higher ponasterone-binding potential than CtUSP-1. Both USP forms demonstrated the ability to activate ecdysteroid-inducible transcription in HeLa cells and the variations in the A/B domain of these forms were not associated with detectable differences in transcriptional activation. Thus, the two forms function similarly. Among species for which USP forms have been reported, Chironomus is the most closely related one evolutionarily to Drosophila. Despite this proximity, a variety of structural differences were noted in both the A/B and E domains of USP between the two species. The Chironomus USP forms lack many of the amino acid residues associated with the ligand-dependent AF2 transactivation function found in all other RXRs and USPs reported so far.

Effects of sputum oscillations and rhDNase in vitro: a combined approach to treat cystic fibrosis lung disease.

Mucolytic treatment with rhDNase is part of the current therapy for cystic fibrosis (CF) lung disease. The Flutter valve, a device for enhancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter valve leads to oscillations of expiratory airflow, improving mucus viscoelasticity and stimulating clearance. The goal of our in vitro study was to evaluate the individual and combined effects of Flutter valve oscillations and rhDNase treatment on the viscoelastic (rheological) properties of CF sputum. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: 1) baseline sample with no treatment applied; 2) application of oscillations generated by airflow through the Flutter valve; 3) incubation at 37 degrees C for 30 min with 10% vol/wt rhDNase (Pulmozyme) to achieve a final concentration of 2.5 microg/mL (approximately 100 nM); 4) combination of Flutter valve oscillations and 10% vol/wt normal saline (0.9% NaCl); 5) combination of Flutter valve oscillations and 10% vol/wt rhDNase at 2.5 microg/mL final concentration. For each protocol, the mucus rigidity index (log G* at 1 rad/s) was measured at baseline and at 30 min. Values are presented as mean+/-SEM. The cough clearability index (CCI) was computed from measurements of mucus viscoelasticity, based on relationships established in model studies. Flutter valve treatment alone did not result in a significant reduction in the rigidity of CF sputum (2.24+/-0.13 vs. 2.11+/-0.13, P=0.19), nor did rhDNase (2.5 microg/mL) alone, although we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensitive to molecular weight reduction. In comparison to individual treatments, combined treatment with Flutter valve oscillations and rhDNase significantly reduced the mucus rigidity to 1.85+/-0.19 from 2.24+/-0.13 (P< 0.001), consequently increasing the predicted clearability of the sputum (from 1.09+/-0.26 to 1.83+/-0.48, P=0.012). These in vitro results suggest that a combination of biochemical treatment (e.g., DNase) and mechanical oscillation may have a better therapeutic potential for mucus clearance in CF lung disease.

Ticlopidine-associated pancytopenia: implications of an acetylsalicylic acid alternative.

Ticlopidine is an antiplatelet agent that has been proven efficacious in preventing vascular events in patients with a history of vasculopathy. Neutropenia is a significant adverse effect and pancytopenia is rarely reported. A fatal case of pancytopenia associated with unmonitored use of ticlopidine is presented. A 59-year-old woman presented with severe pneumonia and profound neutropenia (absolute neutrophil count 0%). She deteriorated with development of acute respiratory distress syndrome and a marked reduction in trilineage hematopoiesis. Despite prompt marrow response to granulocyte macrophage colony-stimulating factor (GM-CSF) and cessation of ticlopidine, appropriate antibiotics and other supportive therapy, she died 17 days after admission. Hematological monitoring is imperative to identify potential complications: if discovered late, there may be a role for GM-CSF for marrow support. Ticlopidine is indicated for patients intolerant of or nonresponsive to acetylsalicylic acid therapy. As the use of ticlopidine increases, clinicians must be aware of potential life-threatening complications associated with its use and monitor appropriately.

Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I.

Treatment with recombinant human deoxyribonuclease I (rhDNase) is currently used as therapy for cystic fibrosis (CF) lung disease. Hypertonic saline (HS) acts as an expectorant promoting mucus secretion and augmenting the volume of sputum. We evaluated the individual and combined effects of HS and rhDNase in vitro on the viscoelasticity of CF sputum. Sputum samples were collected from nine CF patients to use for in vitro testing. Aliquots of CF sputum (0.20 to 0.40 g) were subjected to the following protocols: (1) negative control sample without any treatment; (2) positive control sample, adding 10% volume of normal saline (0.9% NaCl); (3) application of hypertonic saline (HS-3% NaCl); (4) combining approximately 100 nM concentration of rhDNase with protocols 2 and 3. The samples in protocols 2 through 4 were incubated for 30 min at 37 degrees C. For each protocol, CF sputum was analyzed at baseline and at 30 min for spinnability by filancemeter and viscoelasticity by magnetic microrheometry. Spinnability decreased for the sputum samples that were treated with rhDNase, in combination with either HS or normal saline. Treatment with HS alone and combined treatment with rhDNase and HS decreased log G* (the principal viscoelasticity index) to the same degree. Saline alone and rhDNase in normal saline both increased the predicted cough clearability of the sputum; however, the combined treatment with rhDNase and hypertonic saline had the best overall effect on cough clearability. The change in predicted mucociliary clearability, although greatest after HS, was not significant. These in vitro results suggest that combined treatment with rhDNase and HS should be evaluated further as a potential mucotropic approach to augment the clearance of purulent sputum in CF lung disease.

Fatty acid pool size in plasma lipoprotein fractions of cystic fibrosis patients.

The objective of this study was to quantitatively measure the essential fatty acid pools in lipid fractions of plasma lipoproteins and the alteration of these pool sizes after consumption of a physiologic intake of fish oil. Twenty-three cystic fibrosis (CF) patients and 21 normal subjects were supplemented with fish oil, providing 35 mg n-3 fatty acids/kg body wt for 4 wk. Blood was collected pre- and postsupplementation and was quantitatively analyzed to determine the fatty acid pool size in each lipid class of low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and very-low-density lipoproteins. Two 7-d food records were collected to determine total fat and fatty acid intakes. Intakes of protein, carbohydrate, and fat as a percentage of energy and the ratio of polyunsaturated to saturated fats was similar for the CF and control groups. Energy intake was greater for CF subjects. Smaller lipoprotein essential fatty acid pools were observed in CF patients than in control subjects. Healthy subjects had larger essential fatty acid pool sizes in cholesterol ester fractions of HDLs and LDLs than CF subjects. Cholesterol ester and phosphatidylcholine pools transported the majority of essential fatty acids in both CF and control subjects.

Insect nuclear receptors: a developmental and comparative perspective.

The appearance of puffs on the polytene chromosomes of insect salivary glands incubated with 20-hydroxyecdysone provided the first demonstration that steroids act directly at the gene transcriptional level to bring about subsequent cellular changes (Becker, 1959; Clever and Karlson, 1960). Despite that auspicious beginning, learning about the molecular mechanisms that underlie the hormonal regulation of insect development was impeded for many years by the difficulty associated with isolating and identifying rare regulatory factors from limited tissue sources. The advent of recombinant DNA methodology and powerful techniques such as the polymerase chain reaction (PCR) along with the recognition that many important endocrine factors are structurally conserved across a wide range of species has, however, all but eliminated the technical obstacles once facing the insect endocrinologist trying to isolate and study these regulatory molecules. This review will discuss recent progress and recall some earlier experiments concerning the molecular basis of hormonal action in insects focusing primarily on the members of the nuclear hormone receptor superfamily in Drosophila melanogaster. Two members of this family comprise the functional ecdysteroid receptor and at least a dozen other "orphans" have been identified in Drosophila for which no cognate ligand has yet been found. Many of these orphans are regulated by ecdysteroids. A discussion of juvenile hormone binding proteins that are not family members has been included because of their potential impact on nuclear receptor function. As receptor homologues have been identified in other insects, several general ideas concerning insect hormonal regulation have begun to emerge and these will be examined from a comparative point of view.

Effects of combined treatment with rhDNase and airflow oscillations on spinnability of cystic fibrosis sputum in vitro.

Treatment with either rhDNase or high-frequency oscillation has been shown to be effective in improving the physical and transport properties of airway secretions in cystic fibrosis (CF). The objects of this in vitro study was to examine whether combined treatment with oscillation and rhDNase results in greater change of CF sputum spinnability than either treatment by itself. Aliquots of sputum (0.4 g) from eight CF patients were subjected to the following protocols for 15 minutes and then followed for a total of 30 minutes: 1) incubation with 0.04 ml DNase 50 micrograms rhDNase/normal saline (10% dilution) at 37 degrees C to achieve 5 micrograms DNase/g of sputum final concentration; 2) airflow oscillation at 27 Hz similar to the airflow magnitude produced by a commercial high-frequency chest compression (HFCC) device; 3) negative control with no treatment; 4) positive (dilution) control, incubating with 10% saline by volume; 5) combination of DNase and oscillation, and 6) combination of saline and oscillation. For each protocol, sputum spinnability (in mm, mean +/- SD) was measured by means of a filancemeter at baseline, 15, and 30 minutes. Treatment with DNase decreased spinnability significantly more than either saline or oscillation at 15 and 30 minutes (P < 0.02 and P < 0.04, respectively). Incubation with saline or oscillation of CF sputum for 15 and 30 minutes decreased spinnability significantly compared with control. The combination of DNase and oscillation decreased spinnability significantly more than treatment with DNase alone (3.74 +/- 0.45 vs. 6.54 +/- 0.73 at 15 minutes, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Expression and function of the ultraspiracle (usp) gene during development of Drosophila melanogaster.

The usp locus encodes a member of the nuclear hormone receptor superfamily in Drosophila melanogaster that interacts with EcR (ecdysone receptor) to mediate ecdysteroid-induced gene expression. A 2.7-kb usp mRNA was detected at all developmental times tested, although its abundance varied. Among premetamorphic stages, both the 2.7-kb transcript and Usp protein attained their highest levels in the late third larval instar. The 2.7-kb usp transcript was also found in adult stages and a 1.2-kb transcript was detected in the polyadenylated RNA fraction of both mature adult females and early embryos. Aneuploids carrying two usp mutant alleles and a putative variegating usp+ allele often developed deformities of the adult wing disc that apparently resulted from mutational disruption of usp activity before metamorphosis and whose frequency was affected by maternal genotype. Both of the recessive lethal usp mutations associated with this "cleft thorax" phenotype involved substitutions of conserved arginine residues in the DNA-binding domain, although the frequency of the phenotype was not the same for the two alleles. Both mutant proteins retained the ability to form heterodimers with EcR in vitro but showed reduced affinity for an ecdysone response element.

Essential fatty acid metabolism in cultured human airway epithelial cells.

To characterize essential fatty acid metabolism of human airway epithelium, we examined the capacity of epithelial cells to incorporate and desaturate/elongate 18:2(n - 6) and the turnover of phospholipid fatty acyl chains in these cells. Epithelial cells were cultured for 5-7 days and incubated with [1-14C]18:2(n - 6) (1 microCi, 100 nmol). The essential fatty acid profile of the cells was readily modified by 18:2(n - 6) supplementation to culture medium. After 4 h incubation, 32 +/- 5.6 nmol of [1-14C]18:2(n - 6) was incorporated into phospholipids (65 +/- 9.5%, of which 74% was incorporated into phosphatidylcholine (PC)) and neutral lipid (31 +/- 10%) per mg protein of cultured cells. 30 +/- 8% of [1-14C]18:2(n - 6) incorporated, was converted to homologous trienes, tetraenes and pentaenes, the major products being 20:3(n - 6) and 20:4(n - 6). The conversion of 18:2(n - 6) was time-dependent and donor age-related. A higher proportion of 20:3(n - 6) and 20:4(n - 6) was incorporated into phosphatidylinositol (PI) and phosphatidylethanolamine (PE). About 10-15% of total products formed from 18:2(n - 6) was released from membrane to culture medium. Both 20:4(n - 6) and 20:5(n - 3) inhibited 18:2(n - 6) incorporation and desaturation. Rate of incorporation of 18:2(n - 6) was more than either 18:1(n - 9) or 16:0. With pulse-chase studies, the half-life of 18:2(n - 6) in PC, PI and PE was estimated to be 5.5, 6.0 and 7.3 h, respectively. These data indicate active metabolism of essential fatty acids in human airway epithelial cells. This metabolism may play a key role in the regulation of membrane properties and function in these cells.

The chloride channel blocker anthracene 9-carboxylate inhibits fatty acid incorporation into phospholipid in cultured human airway epithelial cells.

This study investigated whether making epithelial cell membranes impermeable to Cl- movement affects incorporation of fatty acids into membrane constituents. Epithelial cells were isolated from human nasal polyps, cultured for 5-7 days, and used to test the effect of anthracene 9-carboxylate (9-AC), known to inhibit Cl- conductance across the epithelial membrane, on the incorporation and desaturation of [1-14C]linoleic acid (C18:2,n-6) in experiments of up to 4 h duration. 9-AC (5 mM) reduced C18:2,n-6 incorporation into phospholipid by 60-70%, and increased incorporation of C18:2,n-6 into triacylglycerol by 50-100%. The decrease in C18:2,n-6 incorporation into phospholipid was rapid and dependent on the concentration of 9-AC. Substitution of extracellular Cl- with gluconate significantly decreased C18:2,n-6 incorporation into phospholipid, suggesting that the effect of 9-AC may occur by inhibiting Cl- conductance. Lipid analysis of cells exposed to 50 microM-C18:2 revealed that, as a consequence of the effect of 9-AC, the level of C18:2,n-6 in cell membrane phospholipid was significantly lowered. The relative rate of C18:2,n-6 desaturation was not apparently changed by 9-AC. These data suggest that Cl- conductance may play a role in fatty acid incorporation into epithelial cell membrane phospholipids.

Neuroleptanalgesia and extracapsular cataract extraction.

Peribulbar and retrobulbar anaesthesia are commonly used techniques in cataract extraction. They offer satisfactory analgesia and akinesia but serious complications although uncommon are consistently reported. Intravenous sedation combined with a facial nerve block offers an alternative method of anaesthesia. This is a retrospective study of patients who underwent extracapsular cataract extraction using this technique between 1 January 1986 and 1 September 1990. The operating conditions were judged to be very suitable with minimal peroperative complications. The postoperative ocular complication rate was low (minimum follow-up 3 months) and no serious medical complications were noted: 93.8% of patients achieved 6/12 vision or better. This study demonstrates that it is possible to achieve satisfactory ocular analgesia and akinesia during cataract extraction under local anaesthesia without the use of a periocular injection.

A specialized home care team does make a difference.

Results of a study done in a large teaching and research facility in Alberta reveal that a specialized home care team can substantially lower the cost of caring for people who are ventilator dependent. With the assistance of a pulmonary physician, the Respiratory Home Care program has shown excellent results. Patients report that they "feel as safe at home as in the hospital", and the savings to the health care system are estimated to be about $2,000,000 per year.