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To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429–32?070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10-8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10-9after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170?kb upstream of the transcription start site of the major transcript for the CADM2gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2in the cingulate cortex (P-value=4 × 10-4). The protein encoded by CADM2is involved in glutamate signaling (P-value=7.22 × 10-15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10-11) and neuron cell-cell adhesion (P-value=1.48 × 10-13). Our findings suggest that genetic variation in the CADM2gene is associated with individual differences in information processing speed.

Ninety culled dairy cows were used in this study and were paired by weight and conformation similarity. Forty-five cows were arterially infused immediately after bleeding with 10% volume by weight of a solution composed of dextrose (.23%), glycerin (.21%), a phosphate blend (.14%) and maltose (.1%). The remaining cows (45) served as controls. In infused carcasses, some quantity of solution retained was in the following order: supraspinatus, chuck > longissimus, loin > semitendinosus, round muscles. Accordingly, percentage of protein, ether-extract able fat, and protein fat-free amounts were lowered (P< .05) and percentage of moisture and moisture protein ratio were raised (P< .05) in the supraspinatus muscle. Tenderness (P< .01) and protein extractability (P< .15) were improved. No difference was observed in water-holding capacity between infused and control carcasses. Percentages of moisture fat-free (r = .85) and protein fat-free (r = -.97) were highly correlated to moisture:protein ratio. Moisture percentage of the fat-free tissue was shown to be a more consistent indicator of added moisture in infused whole carcasses compared with moisture:protein ratio and percentage of protein fat-free. Very low correlations were observed between tenderness, percentage of moisture, percentage of water-holding capacity, and ether-extractable fat. The economics of the infusion process to the beef industry is discussed.

Forecasts from an operational system for predicting global diurnal sea surface temperature (SST) variability are compared against multichannel sea surface temperatures calculated from advanced very high resolution radiometer data from the NOAA-9 satellite. The forecast system consists of an upper-ocean model driven by heat fluxes and wind stresses from an operational global weather prediction model. Visual pattern correlations between observed and forecast diurnal changes in SST are generally favourable, indicating that the forecast system is useful. Some systematic deficiencies are also noted: the forecasts do not reproduce the surprisingly sharp boundaries of diurnal warming regions and underpredict the amplitude of the extreme warming events

1. Transnasal pressure (delta p) in Pa and gas flow in cm3 s‐1 were measured in men breathing gases of different density, assuming flow through each nostril (f) to be half the measured total flow. Measurements were also made in children with allergic rhinitis before and after nasal antigen challenge. 2. Flow always showed evidence of turbulence when transnasal pressure exceeded 40‐80 Pa breathing air and Reynolds number exceeded 2400 (1800 in the presence of nasal obstruction). 3. Changes in effective mean nasal airway diameter (D) after nasal challenge can be determined at points of similar pressure from the relation log (D2/D1) = 0.368 log (f2/f1) when flow is turbulent. 4. Absolute estimates of airway diameter in cm can be obtained from the relation 4.75 log D = 1.75 log f‐‐log delta p+log L‐‐4.756 breathing air when flow is turbulent (since the relation between pressure and flow approximates to that found in a long cylinder) and these estimates are only marginally affected by differing assumptions about nasal airway length (L). 5. Because pressure and flow are non‐linearly related, and changing nasal dimensions have a profound effect on the flow at which turbulence occurs, it is suggested that measures of nasal conductance at delta p greater than or equal to 0.1 kPa are preferable to the more conventional measures of nasal resistance at a specified flow rate.

Exposure of workers applying paraquat to fields of tomatoes and citrus, and diquat to waterways containing water hyacinths and hydrilla, was monitored with dermal a-cellulose pads attached at each of ten body locations and with personal air monitors. Estimated total body exposure for tomato applicators was apparently influenced by tractor type. Exposure levels from highest to lowest were: open tractor > enclosed cab tractor ? high-clearance tractor. Citrus applicators' exposure to paraquat averaged 28.5 mg/hr and 12.2 mg/hr, with tank concentrations of 0.11% and 0.07%, respectively. Diquat applicators received minimal exposure. Respiratory exposure was <0.1% of the total body exposure in all experiments. Urine samples collected periodically for all workers were, with one exception, without detectable pesticide contamination. Use of disposable coveralls and regularly washed impermeable gloves should effectively reduce exposure.

The biology of the arrhenotokous autoparasitoid,Encarsia pergandiellaHoward, was studied in the laboratory on the silverleaf whitefly,Bemisia argentifoliiBellows & Perring. Egg to adult development of parasitoid females averaged ca. 14 days at about 25.3+0.2‡C regardless of whether the whitefly host was reared on tomato, eggplant or squash. While all instars ofB. argentifoliiwere accepted for primary parasitization, a greater percentage of third and fourth instars were parasitized. Mortality of whitefly nymphs in the absence of parasitization did not differ among instars and averaged about 35%. Second instar to pupal parasitoid females were accepted for secondary parasitization although a greater percent of pupal females were parasitized. About 40% of immatureE. pergandiellafemales more than 4 days old died in the absence of secondary parasitization when exposed to adultE. pergandiellafemales.

AbstractLet Abe a semisimple modular annihilator Banach algebra and let LAbe the left regular representation of A. We show how the strong radical of Ais related to the strong radical of LA.

AbstractIn the case when 0 < p< 1 it is proved, using a method of Macphail that the identity map i: lp? lpis not (r, s)-absolutely summing for any r, s.

AbstractLet Gbe a compact group. A sequence of functions in L?(G) is said to be a Rudin-Shapiro sequence(briefly, an RS-sequence) if the following conditions hold: (1) (2) (3) The main purpose here is to prove the following theorem: Theorem: Theorem. Let G be an infinite compact group. Then G has an RS-sequence consisting of trigonometric polynomials.

By the systematic use of Fourier transforms and suitable weight functions L. R. Volevich and B. P. Paneyakh brought many classes of spaces of distributions (including the Sobolev spaces) and their topological duals under the one unifying definition. The main purpose here is to demonstrate that the representation of multipliers between pairs of these spaces (that is, continuous linear operators from one space into another which commute with translations) may be related to the representation of multipliers between Lpand Lq.

Results indicate that there was little difference in the usefulness of the live probe or lean meter in regard to estimating backfat thickness and percentage of either lean or primal cuts. However, the higher relationship for the live probe with both loin lean areas and with fat trim indicated live probe to be a more reliable measure for estimating carcass leanness.

The specific gravity of the untrimmed right ham was found to be closely associated with the specific gravity of the entire carcass with a correlation coefficient of .86. However, cut-out percentages, chemical composition of the ham, loin lean areas, and fat thickness measures were not as closely predicted by ham specific gravity as by carcass specific gravity. The correlation coefficients obtained between ham specific gravity and the above mentioned items were all highly significant.In this study, contrary to previous work, carcass cut-out was more closely associated with live probe and backfat thickness than with specific gravity of the ham. However, specific gravity of the untrimmed ham more closely predicted its chemical composition than lean areas of the loin, carcass length, live probe, or backfat thickness.Results indicated that specific gravity of the ham or carcass was a more reliable indicator of muscling, or actual meatiness, than live probe or backfat thickness. This conclusion was based on a higher correlation of specific gravity and loin lean areas than between fat thickness and lean areas. Added proof was drawn from the closer relation of specific gravity and chemical components than of fat thickness measures and chemical composition.Carcass length showed no significant relationship with cut-out, chemical composition, or exterior fat thickness. Carcass length combined with backfat thickness or live probe gave little advantage over the use of backfat or live probe alone. Dressing percentage was not significantly associated with specific gravity or loin lean area. In this study the lean area of the loin measured at the tenth rib more closely predicted cut-out than the same area measured at the last rib.In general, lean cut-out was more closely associated with other measures of leanness than primal cut-out.

In this study the fat-lean ratio in cross section of the rough loin at the last rib was investigated as a possible measure of carcass leanness. Correlation coefficients of approximately −0.60 between the fat-lean ratio and several measures of carcass cut-out indicated the relationship may be high enough to be useful when it is impossible to obtain cut-out information. However, the area of lean at the 10th rib or last rib was only slightly less reliable than the ratio of fat to lean for estimating cut-out values.Consideration of the relationship between either carcass length or dressing percentage and carcass cut-out indicates that major emphasis should be placed on other methods of measuring leanness.

In determining the suitability of specific gravity of three untrimmed cuts, i.e., the ham, loin, and shoulder, as measures of carcass leanness, it was found that the specific gravity of each of the cuts was closely associated with specific gravity of the entire carcass. The correlation coefficients were +0.94, +0.96, +0.92 for the ham, loin, and shoulder, respectively, when both cuts from the same carcass were used. However, on a single cut, corresponding values were +0.93, +0.91, and +0.87.The somewhat higher correlations for specific gravity of a single ham to other measures of carcass leanness indicated that the untrimmed ham was a more reliable index of the entire carcass than either a single rough loin or untrimmed shoulder. With the exception of the relationship between specific gravity of the single ham and percent primal cuts on a carcass basis, the correlations for specific gravity of a single ham closely paralleled those for specific gravity of the entire carcass in relation to other carcass measures. Specific gravity of either the entire carcass or a single ham proved to be superior to backfat thickness as a measure of carcass leanness.In examination of correlation coefficients by weight groups, indications were obtained that both backfat thickness and length of carcass were better measures of leanness for lighter weight pigs.

Birkhoff's normalizing canonical transformation at an equilibrium of elliptic type with no internal resonance can be built explicitly and recursively, without partial inversions or substitutions, by means of Lie transforms.

Estimates of the cross sectional picture of the loin in 41 live hogs were made utilizing ultrasonic reflection measurements coupled with angles of incidence at a scheduled series of sites over the last rib. Although some subjective judgment was necessarily involved in completing the “ultrasonic plots”, the mean of these estimates of muscle size was not significantly different from the area of the loin eye muscle measured from tracings of the rough loin. The correlation between live estimated area and actual eye muscle area was 0.74. This method of determining muscle size in live swine was time consuming and tedious, thus its usefulness may be restricted for the present to research until further refinement in technique results in sufficient improvement in accuracy for predicting muscle size in breeding stock. Refinement of technique may increase the precision of this tool for measuring leanness in live animals.

The usefulness of an ultrasonic probing technique for measuring thickness of fat and lean tissues was explored with 158 live hogs. Since the procedure of measurement differed in some respects, the data were treated in two groups. Results showed the ultrasonic measurements of fat were highly related to both live probe and backfat thickness.Live probe, backfat, and ultrasonic measurements of fat were equal in value for predicting lean and primal cut-out. Fat thickness measured ultrasonically could be used to predict carcass value, but it offered little advantage over commonly used probing procedures. However, the possibility of applying ultrasonics in the grading of pork carcasses on the rail in a systematic and perhaps automatic manner appears feasible. Ultrasonic estimates of the depth of the loin eye muscle over the center of the back in the live hogs were significantly related to depth and area determinations taken from a tracing. The ultrasonic estimate of lean depth on the carcass was improved when the effect of fat thickness was removed.

Two large scale consumer panels were utilized in evaluating 22 different products differing only in that one group contained boar meat with strong boar aroma, whereas, the other group contained pork without boar odor. The triangle test was utilized to ascertain if panel members could identify the like and unlike samples (boar vs.control). Samples correctly identified were tabulated and subjected to the X2test to ascertain if differences in preferences were statistically significant.In general, products containing boar meat were not readily distinguishable from similar control (no boar odor) products. Results verify the fact that boar meat can be effectively utilized in products eaten without further heating. Although the panel indicated a preference for pure pork sausage made from boar meat and for canned ham from boars, the reverse was true for cured smoked ham where the control was preferred. Possible explanations for these discrepancies are discussed. In final analysis, it appears that boar meat can be utilized in most products as long as the kitchen and dining areas are kept distinctly separate.

Laminar free convection from a nonisothermal horizontal cylinder is analyzed. The wall surface temperature is assumed to be varied in the manner of a1(x/R)2 + a2(x/R)4. Special transformations are devised and employed so that the resulting differential equations and boundary conditions are free of the parameters a1 and a2. These differential equations are solved once and for all; solutions to the original equations for any particular values of a1 and a2 may then be read off easily as linear combinations of the numerical solutions given here. It is found that the dependence of heat transfer from a horizontal cylinder on Prandtl number is practically the same as that from a vertical plate. Furthermore, the heat transfer is greatly influenced by the surface temperature variations.

Comparisons of the starch-gel patterns of uninoculated aseptic control samples from rabbit and pig muscle with similar samples inoculated and incubated with Clostridium perfringens, Salmonella enteritidis, Achromobacter liquefaciens, and Kurthia zopfiiwere made. Results indicated that C. perfringenscaused extensive alteration in the proteins or enzymes, or both, of the sarcoplasmic fraction of porcine muscle, whereas S. enteritidisand S. faecaliscaused complete breakdown of only myoglobin. Neither A. liquefaciensnor K. zopfiishowed any measurable amount of proteolysis in the sarcoplasmic fraction from pig muscle. Although some of the bands in the starch-gel pattern of rabbit muscle decreased in size and intensity of staining, complete proteolysis of any protein fraction was absent for all test organisms. The disc-gel patterns of the 8 murea-soluble proteins showed that C. perfringenscaused extensive proteolysis in pig muscle and a lesser extent of proteolysis in rabbit muscle. None of the other organisms utilized in this study had any measurable effect upon the urea-soluble proteins. In addition, a simple procedure for aseptic isolation of muscle samples for studying meat spoilage is outlined. Results indicate that careful sanitation and cleanliness will give suitable samples for meat spoilage investigations.

The nonsimilar boundary-layer flow and heat transfer of a cone rotating in a forced-flow field are investigated. Numerical solutions are shown for a half-cone angle of 53.5 deg with parameters (vw/ue)2 ranging from 0 to 20, and with Prandtl numbers from 0.2 to 10. With a half-cone angle of 90 deg (so that one has a rotating disk), the degenerate problem is solved in the same manner.

When a local minimum of a function of several variables has been found by use of an algorithm for finding such minima numerically, one often runs the same algorithm many times with different starting values in the hopes of finding a lower minimum. Here, under the assumption that a local minimum is known, a process with analytical criteria is described which sometimes finds smaller local minima in an algorithmic manner.

Suppose that the Hausdorff topological group $ G$ denotes the set of continuous complex-valued functions on $ G$ denote the restrictions to $ {C_c}$ into $ {L^q}(G)$ When $ 1 \leqq p &lt; q \leqq 2$ $ 2 \leqq q &lt; p \leqq \infty $

$\displaystyle (1)\quad L_p^p \subset L_q^q.$ The main result of this paper is that the inclusion in (1) is strict unless $ G$ is infinite

$\displaystyle \bigcup\limits_{1 \leqq q &lt; p} {L_q^q \subsetneqq } L_p^p \subsetneqq \bigcap\limits_{p &lt; q \leqq 2} {L_q^q} $ for $ 1 &lt; p &lt; 2$ and the second inclusion remaining strict when $ p = 1$ $ 2 \leqq p \leqq \infty $ When $ G$ and lacunary subsets of the dual of $ G$ and $ L_q^q$ and respectively.

Myofibrils from pig muscle inoculated and incubated with Pseudomonas fragishowed an extremely disrupted appearance as compared to uninoculated controls. There was an almost complete absence of material in the H zone, marked disruption of the A band (probably myosin), and some loss of dense material from the Z line. These changes indicated that marked proteolysis had occurred. Bacteria observed in spoiled muscle tissue exhibited protrusions or blebs on the outer surface of the cell walls. The blebs appeared to form detached globules that migrated into the muscle mass. Bacteria grown in non-muscle-containing media did not produce blebs, which indicates the blebs were induced by growth on muscle tissue. The possibility that the blebs and globules may contain a proteolytic enzyme responsible for myofibrillar disruption is discussed.

Considerable salt-soluble protein degradation was observed in pork muscle inoculated with Pseudomonas fragi.During a 20-day incubation period at 10 C, the samples proceeded to rank spoilage or putrefaction. There was a large decrease in the salt-soluble protein fraction and a corresponding increase in nonprotein nitrogen. Disc gel electrophoretic patterns showed that breakdown of the salt-soluble proteins had occurred after incubation for 20 days. During incubation for 10 days at 10 C, P. fragiproduced large amounts of extracellular proteolytic activity in ground pork. Most of the proteolytic activity appeared immediately after spoilage occurred. However, a significant increase in the ability to hydrolyze casein and a slight increase in the ability to hydrolyze denatured hemoglobin occurred prior to spoilage.

ANTIBODIES which react with native C3 are present in high titre in adult1and neonatal saliva2. Although they belong to the TgA class they are macromolecules with a sedimentation coefficient of greater than 19S. They are also unusual in that their binding to C3 is dependent on the presence of calcium ions and they can be dissociated from C3 by 0.01 M EDTA1,2. Our preliminary studies on the properties of this antibody had shown that it could activate the complement system and in this paper we report investigations to determine whether this proceeds by way of the classical or alternative pathway.

In 27 cases of acute severe asthma, a loading dose of 5 mg/kg of aminophylline (omitted if already receiving oral theophylline) followed by a continuous infusion of 1 mg/kg per hour gave satisfactory theophylline levels at 4 h and 24 h. Theophylline clearance rates varied widely, vomiting was common, but unrelated to blood theophylline levels.

ANTIBODIES which react with bound complement components, in particular the third component C3, have been found in the parotid saliva of most normal subjects1. These antibodies have several unusual properties2. Their binding to complement is dependent on calcium ions, they can be inhibited by small amounts of native C3 and although they belong to the IgA class they are macromolecules with a sedimentation coefficient greater than 19S. The titres in mixed saliva are substantially lower than in parotid saliva1and the reduction in titre results from the presence of C3 in mixed saliva that combines with the antibody and neutralises its activity. While investigating the possibility that crevicular fluid was the source of C3 in the mouth, we examined samples of saliva from newborn babies. High antibody titres were found in these samples. We report here on the prevalence and properties of this antibody in neonatal saliva.

The type of antibody produced to foods during infancy may predict or influence the subsequent development of food intolerance and atopic disease. We therefore studied IgG antibody production to two common food antigens in 191 unselected healthy term Infants. IgG1, 2, 3 and 4 subclass antibodies to bovine casein and to ovalbumin were measured by an enzyme linked immunosorbent assay on sera collected at 7 days, 3 months and 1 year of age.Antibodies to casein were detected in all IgG subclasses. They were low at 7 days[mean IgG1 261, IgG2 52, IgG3 54, IgG4 125U/ml]and had risen by 3 months[mean IgG1 2325, IgG2 95, IgG3 130, IgG4 376] with similar levels at lyear. In contrast ovalbumin antibodies were restricted to IgGl & 4. The levels on day 7[mean IgG1 1001, IgG4 716 U/ml] had fallen by 3 months[mean IgG1 287,IgG4 108]but had risen again by 12 months[mean IgGl 836, IgG4 135]. The predominant subclass to both antigens was IgG1.We have investigated the relationship of IgG antibody production to maternal antibody levels and to infant feeding practice. Seventeen infants showed defective yeast opsonisation, an abnormality associated with atopy. IgG subclass production in these infants was similar to the group as a whole and to matched controls.

Efficacy of selected compounds from recently developed groups of acaricides was evaluated in 3 winter field experiments for control of Tetranychus urticae Koch on strawberry, The naphthoquinone, DPX-3792 (2-acetyloxy)-3-dodecyl-1,4-naphthalenedione), and the organotin compounds, cyhexatin, hexakis, and R-28627 (S-tricyclohexyltin O,O-diisopropyl phosphorodithioate), effectively reduced mites and their eggs below levels that developed on strawberry foliage treated with water alone. Fruit yields from plants treated with these compounds were as high or higher than were yields from plants to which no acaricides were applied. The cyclopropane compound, ZR-856 (hexadecyl cyclopropanecarboxylate), was effective against T. urticae but reduced yields in 1 experiment. The carbamates, benomyl and oxamyl, were not as effective in reducing mite populations as the aforementioned chemicals but did significantly reduce populations relative to those on plants sprayed with water only.

Two experiments were conducted in Florida to determine the tolerance of 4 strawberry cultivars to Tetranychus urticae Koch by comparing populations of mites on plants treated or not treated with cyhexatin for mite control. Based on percentage reductions of both numbers and weight of marketable fruit in the presence of dense mite populations, ‘Florida Belle’ and ‘Sequoia’ were more tolerant to T. urticae than were ‘Tioga’ and ‘Siletz’. Cyhexatin significantly reduced mite populations on all cultivars. There were no significant differences among cultivars in the number of mites present.

Slow release theophylline is widely used in the management of childhood asthma. Although dosage schedules have been recommended, few studies have assessed the drug in pre-school age group. Over a 9 month period, 49 pre-school children with chronic asthma (age range 1 year 6 months - 5 years 9 months) were started on slow release theophylline using a recommended regime. Mean initial dosage was 18.1 ± 2.3 mg/kg.day in 2 doses. Blood levels ranged from 3-21 mg/lt (mean ± SD 9.1 ± 4.1). The dosage was increased in 23 children because of sub-therapeutic blood levels. 8 patients were non-compliant - 4 denied non-compliance and 4 patients refused to take the preparation. 16 stoppped therapy because of side effects. 6 had behavioural problems, 9 vomiting and 1 nightmares. Symptoms resolved when drug was withdrawn. 13 had satisfactory control of asthma. 12 were deemed treatment failures because of persisting symptoms, hospitalisation or repeated courses of steroids. Outcome might have been improved by a more gradual introduction of therapy and by use of an eight-hourly dosage schedule, but the data indicates that theophylline usage in this age group needs to be critically re-evaluated.

A randomized double-blind study, comparing treatment with an aerosolized antiviral agent, Ribavirin, 20mg/ml saline, and aerosolized saline has been conducted in 26 infants (14 Ribavirin, 12 Placebo) with clinically diagnosed bronchiolitis. Nebulized Ribavirin or normal saline aerosol was given for 18 hours a day for at least 3 days. Identification of Respiratory Syncitial virus was made in nasal secretions from 20 cases (10 Ribavirin, 10 Placebo). Treatment was delivered for an average of 68 hours in the Ribavirin group and 65 in the Placebo group. Three times daily clinical assessment was made of the infants. Trends in 13 out of 14 clinical indices recorded favoured active treatment. Ribavirin aerosol was associated with significantly faster improvement and reduction in cough, crepitations, and respiratory rate (P<.05). In the 20 infants from whose nasal secretions RSV was identified most trends favoured Ribavirin treatment with reduction in chest recession reaching statistical significance (P<.05). No difference was found in the rate of clearance of respiratory syncytial virus. The treatment was well tolerated as judged clinically and from the results of haematological and biochemical studies. These observations suggest nebulized Ribavirin may have a place in the treatment of some cases of bronchiolitis.

The effect of oxygenation of nebulised salbutamol, given with compressed air, was studied in 18 patients (aged 18 months to 9 years) with acute asthma. A Radiometer TCM2 transcutaneous oxygen monitor was used, preliminary studied having shown that this accurately reflects trends in arterial oxygen tension. Heart and respiratory rates were measured at 10 minute intervals and transcutaneous oxygen (TcO2) continuously. Values of TcO2were averaged over 10 minute periods. Given when baseline TcO2was stable, nebulised salbutamol was associated with a rise of TcO2in 9 children (range 1.1 - 13.3 mmHg, mean 5.2) and a fall in 4 (range 1.1 - 7.3 mmHg, mean 4.7) at 10-20 minutes after nebulised therapy. 5 children fell asleep during or shortly after treatment, and all of these showed a fall in TcO2(Range 5.4 - 19, mean 9.8) with the onset of sleep. Heart rate increased in all, this effect being maximal immediately after nebulisation. The changes in TcO2were not predictable on the basis of age, initial TcO2, heart or respiratory rate, though children who fell asleep tended to have higher initial pulse and respiratory rates. These results emphasise the need for caution in the use of home nebulised therapy in acute asthma.

Ketotifen has been used in the treatment of asthma for over six years, but its place in management remains controversial. We aimed to reappraise the efficacy of ketotifen at concentrations of 10-4and 10-6M, on two in-vitro models of bronchoconstriction: actively sensitized guinea pig tracheal strips (G.P.T.), and passively sensitized human bronchial muscle strips (H.B.M.). Experiments were performed on matched pairs of tissues. An initial maximal acetyl choline induced response was obtained for each tissue, and all other contractions expressed as a percentage of this. Cumulative dose response curves [C.D.R.C] to histamine or acetylcholine were constructed, and repeated with or without ketotifen. Maximal antigen induced contractions were also compared. Results were analysed using paired t-tests. Contraction of G.P.T. by histamine and acetylcholine was inhibited by ketotifen, but antigen challenge was not affected. Contraction of H.B.M. by acetyl choline and antigen was inhibited by ketotifen. We were unable to obtain reproducible histamine C.D.R.C.'s for H.B.M. In both models the effect of ketotifen was dose related, with attenuation or loss of efficacy at 10-6M, a level close to that attained in clinical practice. These results support the concept of dose dependancy of clinical efficacy of ketotifen, and suggest that therapeutic trials of even higher doses may be warranted.

A double-blind placebo controlled cross-over trial was carried out to assess the efficacy of ketotifen in pre-school asthmatics. The trial period consisted of a 1 month run-in and two 6 month treatment periods, with ketotifen 1 mg b.d. or placebo, separated by a 1 month wash-out. 47 children with moderate to severe asthma completed the study. There were 29 boys and 18 girls age ranged from 1 yr 10 months to 5 yrs 11 months (mean 4 yr \[mnplus] 1 yr 3 months). In addition to the study treatment, patients were managed conventionally with beta agonists, theophylline, cromoglycate, inhaled oral steroids. Throughout the study attempts were made to reduce medications to the minimum level compatible with good symptom control. Patients were seen monthly (by BGL) and parents completed a diary card between visits. Benefit was assessed by comparing symptoms of asthma and rhinitis, concomitant medication, and parental and physician preference for the two treatment phases. A preliminary analysis of the data suggests that there was an order effect with symptom control improving and concomitant medication increasing throughout the study period. When active and placebo treatments were compared there was little difference with respect to symptom control, or level of concomitant medication. There was no clear preference expressed for active or placebo therapy. Ketotifen was well tolerated and was associated with increased weight gain.