Characterization of the nuclear ribosomal DNA of Euglena gracilis.

A phage lambda recombinant library containing Euglena gracilis genomic DNA was screened for nuclear rDNA sequences. A recombinant phage was isolated that contained an 11.5-kb nuclear rDNA sequence. The 11.5-kb insert was mapped with restriction endonucleases and was shown to represent a complete rDNA repeat unit that carried the genes for the 19S, 25S, 5.8 S and 5 S cytoplasmic rRNAs. The 2000 rDNA repeat units per haploid genome are organized in the form of identical tandem repeats.

Prognostic effect of bundle branch block related to coronary artery bypass grafting.

The incidence and prognostic effect of the development of new perioperative ventricular conduction abnormalities were examined in all patients undergoing coronary artery bypass surgery at Duke University Medical Center between 1976 and 1981. Of the 913 patients included, transient (resolved before discharge) ventricular conduction abnormalities developed in 156 (17%) and persistent (until discharge) changes developed in 126 (14%). Complete right bundle branch block (BBB) was the most frequent type of new ventricular conduction abnormality, followed by left anterior hemiblock and incomplete right BBB (found in 60%, 26%, and 9%, respectively, of all patients with transient changes and 29%, 33% and 26% of all patients with persistent changes). Development of new ventricular conduction abnormalities was most strongly related to date of operation (p less than 0.0001, univariate chi 2 = 122), increasing from 2% transient and 7% persistent in 1976 to 36% transient and 22% persistent in 1981. The incidence was also higher in older patients. Preoperative ejection fraction and number of diseased vessels were related to development of perioperative ventricular conduction abnormalities but were not independently related after adjustment for other baseline characteristics. Contrary to findings in other studies, development of new perioperative ventricular conduction abnormalities, including isolated new left BBB, did not worsen the survival rate in patients followed up to 3 years after surgery.

Effects of nitric oxide synthase inhibition on regional hemodynamics and oxygen transport in endotoxic dogs.

Nitric oxide synthase (NOS) inhibition has been used to increase blood pressure in humans with septic shock despite a lack of data regarding its effects on O2 delivery (QO2). We studied the effects of NG-nitro-L-arginine methyl ester (L-NAME) on systemic, gut, and hindlimb circulations of endotoxic dogs. Twelve dogs were infused with 2 mg/kg of LPS over 1 h followed by 60 mL/kg of 6% dextran over 2 h. Six dogs also received 20 mg/kg of L-NAME, LPS caused mean arterial pressure (MAP), flow and QO2 to whole body, hindlimb and gut to decrease, but O2 uptake (VO2) did not change. Dextran resuscitation alone produced a hyperdynamic state with increased blood flow to or above baseline. With L-NAME, systemic and regional resistances increased twofold and MAP returned to near baseline. Late in the study, these dogs had significantly lower blood flow and QO2 to the gut but maintained VO2 by increasing oxygen extraction to near critical levels. These data suggest that in acute endotoxicosis, L-NAME may significantly improve blood pressure but may markedly encroach on O2 transport reserves to the gut.

Accuracy of three pulse oximeters during exercise and hypoxemia in patients with cystic fibrosis.

To evaluate the reliability of noninvasive oximeters during exercise in patients with cystic fibrosis (CF), we studied 9 patients during exercise tests, using 3 devices (Hewlett-Packard 47201A, Biox-Ohmeda 3700, Nellcor 100), comparing oximetry readings with arterial blood co-oximetry. Fifty samples from preexercise, exercise, and recovery were collected; and paired measurements were analyzed for bias (arterial blood gas SaO2--noninvasive SaO2) and precision (1 SD of the bias). Values were available for the Hewlett-Packard and the Biox-Ohmeda at all 50 collection times. The Nellcor failed to read on four occasions, all during exercise. The accuracy of the Biox-Ohmeda readings was significantly worse during exercise than rest, while the Nellcor and the Hewlett-Packard performance did not differ significantly between exercise and rest. During hypoxemia (SaO2 < 90 percent as determined by co-oximetry on arterial blood), the Biox-Ohmeda and Nellcor consistently overestimated saturation, with mean bias of -6.1 percent and -3.0 percent, respectively. The Hewlett-Packard was more reliable and valid during hypoxemia, with a mean bias of -1.0 percent. The Nellcor read significantly more accurately in the six patients with severe digital clubbing than in the three patients with mild digital clubbing. It is important to be aware of possible limitations of noninvasive oximeters before accepting them as accurate.

Gastrointestinal complications after cardiopulmonary bypass.

Gastrointestinal (GI) complications after surgery requiring cardiopulmonary bypass (CPB) can be serious, often lethal events. In our study, from 1970 through 1981 there were 43 such complications after 5080 CPB cases (0.85%). We noted on annual persistent occurrence of approximately 1%. The overall mortality rate was 63%. The most frequent complication was hemorrhage (usually gastroduodenal). Other complications encountered were pancreatitis, cholecystitis, hyperbilirubinemia, bowel perforations or infarcts, and gastroduodenal alterations. We concluded that GI complications after CPB are associated with a high mortality rate and often occur with other complications. Careful judgment is needed for appropriate diagnosis and therapy.

Airway and alveolar pressures during perfluorocarbon breathing in infant lambs.

Previous studies exploring the utility of liquid breathing using perfluorocarbon have reported proximal airway pressures (Paw) as high as 70 Torr during inspiration, generating concern about the safety of this form of mechanical ventilation. Effects on the pulmonary capillary bed are, however, more likely related to alveolar pressure (PA) than to Paw, and data on PA during liquid breathing are limited. In this study in infant lambs, we reconstructed the pressure waveforms of PA during liquid breathing by using an occlusion technique and compared these with Paw waveforms. Peak PA (18.6 +/- 10.4 Torr) was significantly less than peak Paw (31.5 +/- 10.5 Torr, P less than 0.001), indicating a large resistive pressure drop (14.4 +/- 4.5 Torr) across the bronchial tree. Mean PA (mPA) was very similar to mean Paw (mPaw) [bias = -2.0 Torr, standard error of the average difference = 0.27 Torr, predictive value of mPaw for mPA (r2) = 0.978], suggesting that mPaw, which is easily measured, may be used to estimate mPA during perfluorocarbon liquid breathing. These data show that alveoli do not experience the same large swings in pressure as the proximal airway does during liquid breathing and that simple measurements of mPaw can be used to approximate mPA during liquid breathing.

Partial liquid breathing with perflubron improves arterial oxygenation in acute canine lung injury.

Tidal liquid breathing with perfluorocarbon liquid improves lung mechanics and gas exchange in surfactant-deficient lambs. We asked whether an intratracheal dose of perflubron equal to liquid functional residual capacity (FRC) or less (partial liquid breathing) would alter gas exchange in gas-ventilated, anesthetized, and oleic acid (OA)-injured dogs. We gave eight dogs perflubron in six aliquots, each equal to one-sixth of liquid FRC [sequential dose (SEQ) group], starting 90 min after OA. Two other groups of eight dogs each received a liquid FRC dose of perflubron (60-70 ml/kg) either just before (P-Pre) or 90 min after (P-Post) OA, and eight control (CON) dogs received OA but no perflubron. In CON, SEQ, and P-Post dogs, OA caused a significant decrease in static respiratory system compliance (Crs) (1.50 +/- 0.05 to 1.15 +/- 0.06 ml.cmH2O-1.kg-1) and arterial PO2 (508 +/- 10 to 113 +/- 16 Torr) by minute 90. In P-Pre, P-Post, and after the third dose of perflubron (50% FRC) in SEQ dogs, arterial PO2 was significantly higher than that in the CON dogs but was similar to that in the CON dogs after perflubron removal. Perflubron doses less than two-thirds of liquid FRC were associated with increased Crs compared with CON dogs, but further lung filling caused a decrease in Crs. Lung histology showed widespread edema and hemorrhage and was similar in perflubron and CON dogs. O2 delivery and uptake were well maintained in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of NG-substituted arginines on coronary vascular function after endotoxin.

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation.

There is indirect evidence that tissue hypoxia occurs in human sepsis and surface measures of muscle tissue PO2 (PtiO2) in hypodynamic endotoxic animals are decreased. This study assessed systemic and regional tissue oxygenation in a more relevant model of hyperdynamic endotoxicosis. We isolated venous outflow from the left hindlimb and a segment of ileum in six anesthetized dogs to measure muscle and gut O2 delivery and uptake (VO2) and lactate flux, gut intramucosal pH (pHi) by tonometry, and PtiO2 by multi-point surface electrodes placed on mucosal and serosal surfaces of gut and on muscle. We then infused Escherichia coli lipopolysaccharide (LPS; 2 mg/kg) over 1 h followed by a 2-h infusion of dextran (0.5 ml.kg-1.min-1). LPS infusion significantly decreased systemic and gut VO2, cardiac output (Q), and blood pressure and increased arterial lactate and gut lactate flux. Resuscitation increased Q to above baseline and restored systemic VO2. In response to LPS and then resuscitation, muscle PtiO2 distribution did not change, suggesting little microcirculatory disturbance, although mean PtiO2 first decreased and then increased. In contrast, gut VO2 and pHi remained low and lactate output remained high, despite restoration of gut blood flow. Gut VO2, lactate flux, pHi, and PtiO2 histograms were consistent with a marked redistribution of blood flow within the gut wall, away from the mucosa and toward the muscularis. These data show that, in hyperdynamic acute endotoxemia, skeletal muscle PtiO2 and VO2 are well maintained, but blood flow within the gut is significantly disturbed with mucosal hypoxia.

Raising P50 increases tissue PO2 in canine skeletal muscle but does not affect critical O2 extraction ratio.

Affinity of hemoglobin (Hb) for O2 determines in part the rate of O2 diffusion from capillaries to myocytes by altering capillary PO2. We hypothesized that a decrease in Hb O2 affinity (increased P50) would increase capillary and tissue PO2 (PtiO2) and improve O2 consumption during ischemia. To test this hypothesis, blood flow to the pump-perfused left hindlimb of 18 anesthetized and paralyzed dogs was progressively decreased over 90 min while hindlimb O2 consumption and O2 delivery (QO2) and PtiO2 were measured at the muscle surface. Arterial PO2 was maintained at 150 +/- 10 Torr in all dogs. We increased P50 by 12.3 +/- 0.9 (SE) Torr in nine dogs with RSR-13, an allosteric modifier of Hb. This decreased arterial O2 saturation to 90-92% but increased mean PtiO2 from 35.5 +/- 11.6 to 44.1 +/- 15.2 (SD) Torr (P < 0.05) with no change in controls (n = 9). O2 extraction ratio at critical QO2 was 74 +/- 2% in controls and 79 +/- 1% in RSR-13-treated dogs (P = not significant). PtiO2 was 30-40% higher in the RSR-13-treated group at any QO2 above critical but did not differ between groups below critical QO2. Perfusion heterogeneity and convergence of the dissociation curves near critical QO2 may have mitigated any effect of increased P50 on O2 diffusion. Still, increasing P50 by 12 Torr with RSR-13 significantly increased PtiO2 at QO2 values above critical.

Role of endothelial factors in active hyperemic responses in contracting canine muscle.

We investigated whether endothelium-derived relaxing factor (EDRF) and prostaglandins, which may be released under conditions of increased blood flow, contribute to the active hyperemia in contracting muscle of anesthetized dogs. The venous outflow from the left gastrocnemius muscle was isolated and measured. The tendon was cut and placed in a force transducer. One group served as a control (Con; n = 9); EDRF synthesis was inhibited using N omega-nitro-L-arginine methyl ester (L-NAME) in a second group (n = 9), and a third group (n = 7) received L-NAME and indomethacin (L-NAME+Indo) to inhibit prostaglandin synthesis. After resting measurements, the distal end of the cut sciatic nerve was stimulated to produce isometric contractions at 1, 2, 4, and 6 twitches/s for 6-8 min, separated by 25-min recovery periods. Blood flow and O2 uptake increased linearly from resting values of 11.8 +/- 2.4 and 0.3 +/- 0.05 ml.100 g-1.min-1, respectively, to maximal values of 84.2 +/- 5.1 and 11.1 +/- 0.7 ml.100 g-1.min-1 in the Con group; neither these values nor those for tension development were different from values observed at comparable contraction frequencies in the L-NAME and L-NAME+Indo groups. At rest, resistance was greater (P < 0.05) in both the L-NAME and L-NAME+Indo groups compared with Con, the highest value (P < 0.05) occurring in the L-NAME+Indo group. Muscle resistance decreased (P < 0.05) in all groups at all contraction frequencies; the values were not different among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelial modulation of neural sympathetic vascular tone in canine skeletal muscle.

The effect of nitric oxide synthase (NOS) inhibition and endothelin-A (ETA)-receptor blockade on neural sympathetic control of vascular tone in the gastrocnemius muscle was examined in anesthetized dogs under conditions of constant flow. Muscle perfusion pressure (MPP) was measured before and after NOS inhibition (Nomega-nitro-L-arginine methyl ester; L-NAME) and ETA-receptor blockade [cyclo-(D-Trp-d-Asp-Pro-D-Val-Leu); BQ-123]. Zero and maximum sympathetic nerve activities were achieved by sciatic nerve cold block and stimulation, respectively. In group 1 (n = 6), MPP was measured 1) before nerve cold block, 2) during nerve cold block, and 3) during nerve stimulation. Measurements under these conditions were repeated after L-NAME and then BQ-123. The same protocol was followed in group 2 (n = 6) except that the order of L-NAME and BQ-123 was reversed. MPP and muscle vascular resistance (MVR) increased after L-NAME and then decreased to control values after BQ-123. MVR decreased after BQ-123 alone and, with the addition of L-NAME, increased to a level not different from that observed during the control period. MVR fell during nerve cold block. This response was not affected by administration of L-NAME followed by BQ-123, but it was attenuated by administration of BQ-123 before L-NAME. The constrictor response during sympathetic nerve stimulation was enhanced by L-NAME; no further effect was observed with BQ-123, nor was the response affected when BQ-123 was given first. These findings indicate that endothelin contributes to 1) basal vascular tone in skeletal muscle and 2) the increase in skeletal muscle vascular resistance after NOS inhibition. Finally, nitric oxide "buffers" the degree of constriction in skeletal muscle vasculature during maximal sympathetic stimulation.

Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis.

Our question was whether inhibition of nitric oxide [endothelium-derived relaxing factor (EDRF)/NO] production in an in situ vascularly isolated but innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O2 extraction during ischemic (IH) or hypoxic hypoxia (HH). After a control period, we gave NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min-1.kg-1 with PO2 maintained at approximately 110 Torr. In HH, PO2 was lowered from 107 to 28 Torr with flow at 78 ml.min-1.kg-1. Total O2 delivery was lowered to approximately 5 ml.min-1.kg-1 in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.21 +/- 0.25 peripheral resistance units (PRU; P < 0.05) after L-NAME infusion and hindlimb O2 uptake increased from 3.9 +/- 0.2 to 4.5 +/- 0.3 ml.min-1.kg-1 (P < 0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P < 0.05) and from 1.03 +/- 0.06 to 0.82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreased from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P < 0.05) and from 2.04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no differences in O2 extraction ratio (0.72) or in O2 uptake between groups during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis.

The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). Arterial inflow and venous outflow from the hindlimb were isolated, and the paw was excluded from the circulation. Pump perfusion from the right femoral artery kept the hindlimb perfusion pressure near the auto-perfused level. Six anesthetized dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20 mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 remained at control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg-1.min-1 60 min after L-NAME (P < 0.05) and remained at that level for the duration of the experiment. Cardiac output was significantly higher in the D-NAME group than in the L-NAME group at 60 min. After L-NAME, QL fell 24% but VO2 increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2, despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle.

O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating a significant O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.

ATP-sensitive K+ channel blockade impairs O2 extraction during progressive ischemia in pig hindlimb.

Tissues maintain O2 consumption (VO2) when blood flow and O2 delivery (DO2) are decreased by better matching of blood flow to meet local cellular O2 demand, a process that increases extraction of available O2. This study tested the hypothesis that ATP-sensitive K+ channels play a significant role in the response of pig hindlimb to ischemia. We pump perfused the vascularly isolated but innervated right hindlimb of 14 anesthetized pigs with normoxic blood while measuring hindlimb DO2, VO2, perfusion pressure, and cytochrome aa3 redox state. In one-half of the pigs, the pump-perfused hindlimb was also infused with 10 micrograms.min-1.kg-1 of glibenclamide, a potent blocker of ATP-sensitive K+ channels. Control animals were infused with 5% glucose solution alone. Blood flow was then progressively reduced in both groups in 10 steps at 10-min intervals. Glibenclamide had no effect on any preischemic hindlimb or systemic measurements. Hindlimb VO2 and cytochrome aa3 redox state began to decrease at a significantly higher DO2 in glibenclamide-treated compared with control pigs. At this critical DO2, the O2 extraction ratio (VO2/DO2) was 53 +/- 4% in the glibenclamide group and 73 +/- 5% in the control group (P < 0.05). Hindlimb vascular resistance increased significantly with ischemia in the glibenclamide group but did not change in the control group. We conclude that ATP-sensitive K+ channels may be importantly involved in the vascular recruitment response that tried to meet tissue O2 needs as blood flow was progressively reduced in the pig hindlimb.

Evaluation of a HSV specific monoclonal antibody reagent for laboratory diagnosis of herpes simplex virus infection.

A new FITC-conjugated HSV specific monoclonal antibody reagent (Syva Co., Palo Alto, Ca) was evaluated for the confirmation of HSV clinical isolates. The reagent was also compared to type-specific monoclonal antibodies for the pre-CPE detection of HSV from clinical specimens in centrifugation culture and by direct examination of specimens smears by direct immunofluorescent antibody staining (DFA). HSV was isolated from 75 of 232 specimens (32%). All 75 isolates were confirmed with both the type-specific antibodies and the HSV-specific reagent. In centrifugation culture HSV was detected in 36 of 105 (34%) specimens. The HSV specific reagent detected all 36 specimens that were positive with the type-specific reagents. HSV infection was diagnosed by DFA in 31 of 50 (62%) specimen smears. The HSV-specific reagent detected all 31 positive specimens. This reagent confirmed and detected all HSV positive specimens that were positive by the type-specific monoclonal antibody reagents. The reagent contains monoclonal antibodies specific for both HSV1 and HSV2 in a single mixture, which produces a highly sensitive HSV FA staining reagent.

Lengthened intraaortic balloon tubing for intraoperative use.

The intraaortic balloon pump (IABP) is being used with increasing frequency during surgical procedures. The standard length of balloon tubing requires the IABP console to be close to the operating table. This creates a possibility of contamination. A longer balloon tubing is described that permits an increased distance between console and operating table without decreasing effective augmentation.

Use of survey data and small area statistics to assess the link between individual morbidity and neighbourhood deprivation.

STUDY OBJECTIVE: The aim of the study was to examine the relationship between sociogeographic factors and health, using a particular social indicator of neighbourhood deprivation. DESIGN: The study analysed the relationship between health problems (reported by randomly selected respondents to a household survey) and an area social indicator for the neighbourhoods where the respondents lived (based on census data). The area social indicator tested was the underprivileged areas indicator developed by the St Mary's Hospital Department of General Practice, London. Generalised linear interactive modelling with a logistic model was used to test the strength of the relationship between social indicators and morbidity, and to calculate the probability of reporting illness or consultations for survey respondents living in different types of area. SETTING: The study population was derived from three London health districts and their corresponding census enumeration districts. PARTICIPANTS: Responses were obtained from 738 households drawn from the local taxation evaluation list (66% of those sampled), and 1384 persons over 16 participated in the survey (94% of eligible adults in households surveyed). Of these, 1221 provided complete data on health problems. The survey population was considered representative of the general population in the areas studied since its characteristics were similar to those reported for the population as a whole in the 1981 census. RESULTS: Within different age and sex groups, those living in very deprived areas, with high underprivileged area scores, were more likely to consult their doctor and to report various indicators of poor health than those living in privileged areas, with low underprivileged area scores. CONCLUSIONS: The underprivileged areas index may provide a useful surrogate indicator to estimate morbidity and use of general practitioner services in small areas. It is likely to be most effective in areas where sociodemographic profiles of the local population are highly contrasting.

Central and peripheral prostaglandins are involved in sickness behavior in birds.

Many of the behavioral manifestations of mammals and birds following infection are now recognized as important mechanisms for maintaining homeostasis and promoting recovery. To investigate the role of prostaglandins (PGs) in the behavioral and physiological effects of lipopolysaccharide (LPS) in birds, chickens were injected with indomethacin (Ind) peripherally (IP, 5 mg) or centrally (ICV, 100 micrograms) and their behavior and body temperature following a challenge IP injection of LPS (2.5 mg) were assessed at 1 and 2 h, respectively. Pretreatment with Ind IP or ICV completely inhibited the hyperthermia caused by LPS. Ind injected IP but not ICV significantly attenuated the LPS-induced anorexia. The drowsiness caused by LPS was completely inhibited by Ind injected IP and partially inhibited by Ind administered ICV. These results are interpreted to indicate that LPS induces hyperthermia in the chicken by activating a PG system in the brain. Peripheral PGs appear to be involved in the anorectic response to LPS, whereas drowsiness caused by LPS may involve both peripheral and central PGs. These data are consistent with the hypothesis that multiple PG systems are activated during the acute-phase response, which may explain the dissociation between mechanisms controlling the behavioral and physiological responses to infection.