Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

PURPOSE: To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D). METHODS: We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers. RESULTS: Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as 'higher-risk', eliciting significantly higher fibrinogen (+ 1514 ± 594 µg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m2; P < 0.001), and lower mean eGDR (- 3.98 ± 1.07; P < 0.001). CONCLUSIONS: Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D. TRIAL REGISTRATION: ISRCTN4081115; registered 27 June 2017.

Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study.

AIM: Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes. METHODS: Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units. RESULTS: Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group. CONCLUSIONS: We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes.

Heavy-resistance exercise-induced increases in jump performance are not explained by changes in neuromuscular function.

Post-activation potentiation (PAP) is the increased involuntary muscle twitch response to stimulation following strong contraction. The enhancement to whole-body explosive muscular performance (PE) after heavy-resistance exercise is often attributed to modulations in neuromuscular function that are proposed to reflect PAP, but the evidence to support this is equivocal. We assessed the neuromuscular basis of PE using transcranial magnetic stimulation (TMS) of the primary motor cortex, and electrical stimulation of the femoral nerve. Eleven male athletes performed heavy-resistance exercise with measures of countermovement jump (CMJ) pre- and 8 min post-exercise. Pre-exercise and after the final CMJ, single- and paired-pulse TMS were delivered during submaximal isometric knee-extensor contractions to measure corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), with motor evoked potentials recorded from rectus femoris. Twitch responses to motor nerve stimulation during and post maximum-knee-extensor contractions were studied to quantify voluntary activation (VA) and potentiated twitch (Qtw,pot ). The experimental protocol successfully induced PE (+4 ± 1% change in CMJ, P = 0.01), but no changes were observed for maximum voluntary force, VA, corticospinal excitability, SICI or ICF (all P > 0.05), and Qtw,pot declined (P < 0.001). An enhancement of muscular performance after heavy-resistance exercise was not accompanied by PAP, or changes in measures of neuromuscular function.

Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with Type 1 diabetes.

AIMS: To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes. METHODS: Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05). RESULTS: Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l). CONCLUSIONS: Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes.

Similar magnitude of post-exercise hyperglycemia despite manipulating resistance exercise intensity in type 1 diabetes individuals.

The aim of this study was to compare the glycemic and glucoregulatory hormone responses to low- and moderate-intensity morning resistance exercise (RE) sessions in type 1 diabetes (T1DM). Following maximal strength assessments (1RM), eight T1DM (HbA1C :72 ± 12 mmol/mol, age:34 ± 7 years, body mass index:25.7 ± 1.6 kg/m(2) ) participants attended the research facility on two separate occasions, having fasted and taken their usual basal insulin but omitting rapid-acting insulin. Participants performed six exercises for two sets of 20 repetitions at 30%1RM during one session [low-intensity RE session (LOW)] and two sets of 10 repetitions at 60%1RM during another session [moderate-intensity RE session (MOD)], followed by 65-min recovery. Sessions were matched for total mass lifted (kg). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using analysis of variance (P ≤ 0.05). There were no hypoglycemic occurrences throughout the study. Blood glucose rose similarly between sessions during exercise (P = 0.382), remaining comparable between sessions throughout recovery (P > 0.05). There was no effect of RE intensity on metabolic acidosis (P > 0.05) or peak growth hormone responses (P = 0.644), but a tendency for greater catecholamine responses under LOW (individualized peak concentrations: adrenaline MOD 0.55 ± 0.13 vs LOW 1.04 ± 0.37 nmol/L, P = 0.155; noradrenaline MOD 4.59 ± 0.86 vs LOW 7.11 ± 1.82 nmol/L, P = 0.082). The magnitude of post-exercise hyperglycemia does not differ between equal volume low and moderate intensity RE sessions performed in the morning.

Simulated games activity vs continuous running exercise: a novel comparison of the glycemic and metabolic responses in T1DM patients.

To compare the glycemic and metabolic responses to simulated intermittent games activity and continuous running exercise in type 1 diabetes. Nine patients (seven male, two female; 35 ± 4 years; HbA1c 8.1 ± 0.2%/65 ± 2 mmol/mol) treated on a basal-bolus regimen completed two main trials, a continuous treadmill run (CON) or an intermittent running protocol (INT). Patients arrived to the laboratory fasted at ∼ 08:00 h, replicating their usual pre-exercise meal and administering a 50% reduced dose of rapid-acting insulin before exercising. Blood glucose (BG), K(+) , Na(++) , pH, triglycerides, serum cortisol and NEFA were measured at baseline and for 60 min post-exercise. Interstitial glucose was measured for a further 23 h under free-living conditions. Following exercise, BG declined under both conditions but was less under INT (INT -1.1 ± 1.4 vs CON -5.3 ± 0.4 mmol/L, P = 0.037), meaning more patients experienced hypoglycemia (BG ≤ 3.5 mmol/L; CON n = 3 vs INT n = 2) but less hyperglycemia (BG ≥ 10.9 mmol/L; CON n = 0 vs INT n = 6) under CON. Blood lactate was significantly greater, and pH lower, with a temporal delay in K(+) under INT (P < 0.05). No conditional differences were observed in other measures during this time, or in interstitial glucose concentrations during the remaining 23 h after exercise. Simulated games activity carries a lower risk of early, but not late-onset hypoglycemia than continuous running exercise in type 1 diabetes.

Impact of single and multiple sets of resistance exercise in type 1 diabetes.

To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38 ± 6 years, HbA1C : 8.7 ± 1.0%/71 ± 11 mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid-acting insulin. Participants completed a 1SET (14 min), 2SET (28 min), 3SET (42 min) RE session (eight exercises × 10 repetitions) at 67 ± 3% one-repetition-maximum followed by 60-min recovery, or a resting trial (CON). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using repeated-measures analysis of variance (P ≤ 0.05). RE did not induce hypoglycemia (BG < 4 mmol/L). During recovery, blood glucose (BG) concentrations remained above pre-exercise after 1SET (15-60 min, P < 0.05) and 2SET (0-60 min, P < 0.05) but comparable (P > 0.05) with pre-exercise after 3SET. BGIAUC(area-under-curve) (mmol/L/60 min) was greater after 1SET and 2SET vs CON (1SET 103.6 ± 36.9 and 2SET 128.7 ± 26.1 vs CON -24.3 ± 15.2, P < 0.05), but similar between 3SET and CON (3SET 40.7 ± 59.3, P > 0.05). Under all trials, plasma creatine kinase levels at 24 h post-exercise were similar (P > 0.05) to pre-exercise. RE does not induce acute hypoglycemia or damage muscle. BG progressively rose after one and two sets of RE. However, inclusion of a third set attenuated exercise-induced hyperglycemia and returned BG to that of a non-exercise trial.

Reductions in resistance exercise-induced hyperglycaemic episodes are associated with circulating interleukin-6 in type 1 diabetes.

AIMS: To determine the influence of different volumes of resistance exercise on circulating interleukin-6 (IL-6) and to explore the relationships between IL-6 and glycaemia. METHODS: Eight participants with complication-free type 1 diabetes, whose mean ± SEM age was 38 (6) years, mean ± SEM HbA(1c) concentration was 71 ±11 mmol/mol (8.7 ±1.0%) and mean ± SEM type 1 diabetes duration was 15 ±13 years, attended the research facility after an overnight fast on four separate occasions, having administered their basal insulin the night before (glargine 27.5±3.1U, n=8), but omitted morning rapid-acting insulin. Participants completed either a one-set (14-min), two-set (28-min), or three-set (42-min) resistance exercise trial (eight exercises × 10 repetitions) at 67±3% one-repetition maximum followed by a 60-min recovery, or a resting control trial. Venous blood samples were taken before and after exercise. Data were analysed using repeated-measures ANOVA (P≤0.05). RESULTS: Whereas IL-6 levels remained similar to baseline levels after one set of resistance exercises (30 min, P=0.287; 60 min, P=0.318), IL-6 levels were > baseline levels at 60 min post-exercise after a two-set exercise trial (2.94 ± 0.94 pg/ml, P=0.002) and doubled at both 30 min (4.01 ± 1.00 pg/ml, P=0.048) and 60 min (4.28 ± 1.25 pg/ml, P=0.084) post-exercise after the three-set resistance exercise trial. Post-exercise blood glucose area under the curve (mmol/l/60 min) was greater after both the one-set (P=0.025) and two-set trials (P=0.008), than after the control trial, but similar between the three-set trial and the control trial (P=0.240). The rise in IL-6 from baseline to peak concentration significantly correlated inversely with blood glucose area under the curve (r=-0.65, P=0.041). CONCLUSIONS: Circulating IL-6 is increased by resistance exercise in a volume-dependent manner, and resistance exercise-induced increases in IL-6 correlated with reductions in post-exercise hyperglycaemia in type 1 diabetes, suggesting a role for IL-6 in improving post-resistance exercise glycaemic disturbances in type 1 diabetes.

Strength and power predictors of sprinting performance in professional rugby players.

AIM: The ability to accelerate and attain high levels of speed is an essential component of success in team sports; however, the physical qualities that underpin these activities remain unclear. This study aimed to determine some of the key strength and power predictors of speed within professional rugby union players. METHODS: Twenty professional male rugby union players participated in this study. Subjects were tested for speed (0-10 m sprint and a flying 10 m sprint), strength (3 repetition maximum squat), lower body power (countermovement jumps [CMJ] and drop jumps [DJ]), reactive strength and leg spring stiffness. The strength and power variables were expressed as absolute values and relative values for analysis. RESULTS: Both relative strength (r=-0.55, P<0.05) and relative power (-0.82, P<0.01) were negatively correlated with 10 m time. Leg spring stiffness and DJ contact time were also related to the flying 10 m time (r=-0.46 and 0.47, respectively, P<0.05) while reactive strength index was negatively related to both the 10 m and flying 10 m times (r=-0.60 and r=-0.62, P<0.05). CONCLUSION: This study provides an insight into those physical attributes that underpin sprinting performance in professional rugby union players and specifically highlights the importance of relative strength and power in the expression and development of different speed components (e.g. acceleration, maximum velocity).

Impact of pre-exercise rapid-acting insulin reductions on ketogenesis following running in Type 1 diabetes.

AIM: This study examined the effects of reductions to pre-exercise rapid-acting insulin dose on changes in blood beta-hydroxybutyrate, glucose, acid-base balance and counter-regulatory hormone responses to prolonged running in individuals with Type 1 diabetes. METHODS: Following ethical approval, seven participants with Type 1 diabetes (34±2 years, BMI 27±1 kg/m(2) ) completed this study. After preliminary testing, participants attended the laboratory four times, each time consuming a 1.12 MJ meal (60 g carbohydrate, 2 g fat, 2 g protein), with randomized amounts of their rapid-acting insulin: Full dose (mean 7.3±0.2 units), 75% dose (mean 5.4±0.1 units), 50% dose (mean 3.7±0.1 units) or 25% dose (mean 1.8±0.1 units). After 2-h rest, participants completed 45 min running at 70±1% peak rate of oxygen consumption (VO(2peak) ). Blood metabolites and hormones were recorded over the 2-h rest and 3-h recovery. Data were analysed using repeated-measures ANOVA. RESULTS: Serum insulin peaked at 60 min in all conditions and was lowest after 25% insulin dose compared with full dose (P=0.03). After the 25% insulin dose immediately pre-exercise glucose concentration was higher than after the full or 50% dose (P<0.05). Resting beta-hydroxybutyrate gradually decreased during 2-h rest (P<0.05) with a similar post-exercise peak of beta-hydroxybutyrate at 3 h (P>0.05). Post-exercise blood pH increased for 5 min to a similar extent with all insulin doses , but the rise with the 25% dose was less compared with the full dose (P=0.01). Blood lactate and plasma catecholamines increased after running similarly with all insulin reduction conditions (P<0.05). Blood glucose area under the curve (BG(auc) ) after the 25% insulin dose was greater than after the 75% dose (P=0.02). CONCLUSION: Ketogenesis following running was not influenced by reductions in pre-exercise rapid-acting insulin dose. This important preparatory strategy aids preservation of blood glucose but poses no greater risk to exercise-induced ketone body formation.

Isolation and characterization of temperature-sensitive respiratory mutants of Neurospora crassa.

Filtration-enrichment and inositol-less death methods of mutant isolation, coupled with a screen for cyanide-insensitive respiration, proved to be highly efficient methods for isolating temperature-sensitive (ts) nuclear Neurospora mutants having defective respiration. Eighteen different ts respiratory mutants have been isolated. Most of them are pleiotropic and defective in one or more of the following phenotypes: cytochrome aa3, b, and c (individual or multiple defects); oligomycin inhibition of ATPase activity; respiration and its inhibition by KCN and salicyl hydroxamic acid; and growth rates in liquid and solid media at 25 degrees and 38 degrees. Among these mutants are the first cytochrome c mutant of Neurospora and an extranuclear ts ATPase mutant. An added bonus was the fact that over half of the mutants were affected either in ribosome assembly or in protein synthesis in the mitochondrion. We have yet to find any mutants completely lacking activities associated with the respiratory chain. However, the wide spectrum of mutants isolated here, along with those currently available, constitutes a considerable resource for investigating respiration in obligate aerobes.

Technetium-99m-DMSA studies in pediatric urinary infection.

UNLABELLED: Urinary tract infection (UTI) is a common condition in children and may lead to renal scarring with a risk of later hypertension and renal insufficiency. We made a cross-sectional study of the 99mTc-DMSA findings in 496 children referred for following symptomatic UTI to a Department of Nuclear Medicine and we categorized the results, to provide a framework for further study. METHOD: A standard 99mTc-DMSA protocol was used to study 496 children (157 males, 339 females) aged from birth to 14 yr. Findings were classified according to the image appearance and relative function of each kidney. These were related to age, sex, history and timing of UTI and the results on micturating cysto-urethrography (MCU). RESULTS: Images were normal, with function within limits (45%-50% in one kidney), in approximately half the boys and girls studied. The other images were classified as equivocal in 68 children, abnormal unilaterally in 105 and bilaterally in 76, and they were subdivided according to the image appearance. No image changes could be identified that were specifically associated with acute UTI. Diffuse change alone was uncommon. A high proportion of abnormal images was found in infant boys, older girls with recurrent UTI and those children with vesico-ureteric reflux (VUR). Of the bilateral abnormal images, 98% were seen in children with VUR. CONCLUSION: Our findings suggest that infective renal change may be superimposed on underlying congenital lesions (perhaps detectable antenatally) or may be acquired following UTI in the presence of reflux and are thus potentially preventable. This study also suggests that VUR is almost certain to have occurred in a child who has bilateral abnormal 99mTc-DMSA images following UTI and is also commonly present in those with definite unilateral defects.

Safety and immunogenicity of a bivalent Haemophilus influenzae type b/hepatitis B vaccine in healthy infants. Hib-HB Vaccine Study Group.

OBJECTIVE: To assess the safety, tolerability and immunogenicity of COMVAX, a liquid, bivalent Haemophilus influenzae type b-hepatitis B vaccine, containing the polyribosylribitol phosphate (PRP)-Neisseria meningitidis outer membrane protein complex conjugate used in the Hib vaccine, PedvaxHIB, and the yeast-derived hepatitis B surface antigen (HBsAg) used in the HB vaccine, RECOMBIVAX HB. DESIGN: Eight hundred eighty-two healthy infants, approximately 2 months of age, were enrolled in an open, multicenter (n = 11) clinical trial and randomized to receive either COMVAX (7.5 micrograms of PRP/5 micrograms of HBsAg in 0.5 ml) or concurrent injections of the liquid formulation of PedvaxHIB (P) (7.5 micrograms of PRP in 0.5 ml) and RECOMBIVAX HB (R) (5 micrograms of HBsAg in 0.5 ml) at 2, 4 and 12 or 15 months of age. Safety and tolerability were monitored after each injection. The serum concentrations of anti-PRP and anti-HBs were determined at the time of each vaccination, 2 months after the second vaccination and 1 month after the third vaccination. RESULTS: COMVAX was well-tolerated and proved to be immunologically comparable with a series of concomitant P+R injections. There were no serious adverse experiences attributable to the study vaccines. The most commonly reported nonserious adverse experiences were all events prelisted on diary cards given to parents. These included generally mild and transient signs of inflammation at the injection site (pain/ soreness, erythema, swelling/induration), somnolence and irritability. Because children are at peak risk of invasive Hib disease during the first year of life, 6 months of age (2 months after the second dose of vaccine) was designated the time of primary interest with regard to the development of anti-PRP. At that time 94.8% of the infants given COMVAX had > 0.15 microgram/ml of anti-PRP and 72.4% had > 1.0 microgram/ ml, with a geometric mean concentration (GMC) of 2.5 micrograms/ml, compared with 95.2%, 76.3% and 2.8 micrograms/ml, respectively, in recipients of P+R. The third injection given at 12 or 15 months of age induced a secondary rise in antibody. The proportions with > 0.15 microgram/ml and > 1.0 microgram/ml of anti-PRP increased to 99.3 and 92.6%, respectively, and the GMC rose to 9.5 micrograms/ml among COMVAX recipients, compared with 98.9%, 92.3% and 10.2 micrograms/ml in children given concurrent injections of P+R. In contrast to Hib few infants in countries with low endemicity of HBV infection are at near term risk of exposure to virus. Consequently the anti-HBs response after the last dose of vaccine was designated the outcome of primary interest. At 13 to 16 months of age (1 month after the third dose of vaccine) 98.4% of children given COMVAX had a protective anti-HBs concentration of > or = 10 mIU/ml with a GMC of 4468 mIU/ml, compared with 100% and a GMC of 6944 mIU/ml among children given P+R. CONCLUSIONS: COMVAX is well-tolerated by healthy infants and can induce immunity against invasive Hib disease and HBV infection using only three injections compared with six injections if separate courses of monovalent PedvaxHIB and RECOMBIVAX HB are given.

Evaluation of a passive hemagglutination test kit for the detection of rubella antibodies.

RUBACELL (Abbott Laboratories), a commercial test kit for the detection of rubella antibodies that utilizes the principle of passive hemagglutination (PHA), was compared with a standard hemagglutination-inhibition (HI) assay procedure. The PHA test gives a qualitative yes/no result suitable for pregravidic determination of immune status. The procedure is technically simple and requires less than half the time needed for the HI assay. Four of 61 sera that were negative with HI assay tested as indeterminate or as falsely positive using the RUBACELL procedure.

Antepartum detection of macrosomic fetus: clinical versus sonographic, including soft-tissue measurements.

OBJECTIVE: To compare clinical and sonographic estimates of birth weights with five new estimation techniques that involve measurements of soft tissue, for identifying newborns with birth weights of at least 4000 g. METHODS: Over 1 year, each woman at or after 36 weeks' gestation and suspected of having a macrosomic fetus had clinical and sonographic estimates of fetal weight (EFW) based on femur length (FL) and head and abdominal circumference, followed by five additional ways to identify excessive growth: cheek-to-cheek diameter, thigh soft tissue, ratio of thigh soft tissue to FL, upper arm subcutaneous tissue, and EFW derived from it. Areas (+/- standard error) of receiver operating characteristic (ROC) curves were calculated and compared with the area under the nondiagnostic line. P <.05 was considered statistically significant. RESULTS: Among 100 women recruited, 28 newborns weighed 4000 g or more. The areas under the ROC curves with clinical (0.72 +/- 0.06) and sonographic predictions using biometric characteristics (0.73 +/- 0.06) had the highest but similar accuracies (P.05). Three of the five newer methods (upper arm or thigh subcutaneous tissue and ratio of thigh subcutaneous tissue to FL) were poor diagnostic tests (range of areas under ROC 0.52 +/- 0.06 to 0.58 +/- 0.07). Estimated fetal weight based on upper arm soft tissue thickness and cheek-to-cheek diameter (areas 0.70 +/- 0.06 and 0.67 +/- 0.06, respectively) were not significantly better than clinical predictions (P.05) for detecting macrosomic fetuses. About 110 macrosomic and nonmacrosomic infants combined would be needed to have 80% power to detect a difference between ROC curves with areas of 0.58 (thigh subcutaneous tissue) and 0.72 (clinical estimate). CONCLUSION: ROC curves indicated that measurements of soft tissue are not superior to clinical or sonographic predictions in identifying fetuses with weights of at least 4000 g.

Antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines.

OBJECTIVE: To confirm that children given a bivalent Haemophilus influenzae type b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R(II)) have satisfactory antibody responses to all antigens. DESIGN: 126 healthy 2-month-old infants were scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4 months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age; OPV at 4 and 14 to 15 months of age), DTaP and M-M-R(II) (14 to 15 months of age). A response was judged "adequate" if the lower bound of the 95% confidence interval on the proportion of vaccinees having a critical antibody level was <10 percentage points below prediction. RESULTS: Antibodies to hepatitis B virus surface antigen, H. influenzae polysaccharide, diphtheria toxin, tetanus toxin, pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus all equalled or exceeded expected levels. Antibodies to rubella virus and pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly, and in the case of rubella significantly, below predicted levels. Antibodies to poliovirus types 1 and 3 were also below expectation after 2 doses of polio vaccine but were adequate following a third dose of vaccine. CONCLUSION: Concurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a booster dose of DTaP, OPV, IPV, or M-M-R(II) was well tolerated and, with the possible exception of rubella, did not substantially impair the antibody response to any antigen.

Isolation of serotonin from the accessory salivary glands of the marine snail Nucella lapillus.

We report here the presence of a bioactive compound in the secretion of the accessory salivary glands (ASGs) of Nucella lapillus. We have purified the compound using HPLC and identified it as serotonin by mass spectrometry, UV spectroscopy, HPLC and capillary electrophoresis. Serotonin was not found in the secretions of the acinous salivary glands or the hypobranchial gland. The amount of serotonin in the secretion of the ASGs does not show seasonal or regional variation.

Present of a toxin in the salivary glands of the marine snail Cymatium intermedius that targets nicotinic acetylcholine receptors.

Presence of a toxin in the salivary glands of the marine snail Cymatium intermedius that targets nicotinic acetylcholine receptors. Toxicon 36, 25-29, 1998.-We present evidence of a neurotoxin from the salivary glands of Cymatium intermedius that displays acetylcholine-like effects on vertebrate (mouse ileum) and invertebrate (molluscan smooth muscle; molluscan heart; leech body wall) tissues. These effects were completely blocked by (+)-tubocurarine (10-100 muM) but not by atropine (up to 200 muM) suggesting that the toxin targets nicotinic-like acetylcholine receptors. This affirms the proposal that this genus may overcome their prey with a paralytic secretion.

Overview of clinical studies with hepatitis B vaccine made by recombinant DNA.

The Merck, Sharp and Dohme hepatitis B vaccine formulated from HBsAg produced by a recombinant strain of Saccharomyces cerevisiae has proven to be highly immunogenic and safe. A 10 micrograms dose of the vaccine produced an anti-HBs response of greater than or equal to 10 IU/l in 91% or more of healthy adults who completed the three-dose regimen. Children responded well to all levels of vaccine antigen utilised but developed maximum anti-HBs titres with 5 micrograms doses. The age of the vaccine recipient affected responsiveness. Younger adults (20-29 years) responded more rapidly and with higher anti-HBs titres than did older adults (greater than or equal to 50 years). Children responded faster and with higher anti-HBs levels than younger adults. Clinical reactions reported after vaccination were mild and transient.

The localization of myocardial ischaemia with technetium-99m methoxy isobutyl isonitrile and single photon emission computed tomography.

Thirty-two patients with suspected coronary artery disease were studied by single photon emission computed tomography (SPECT) imaging with oblique reconstructions of the myocardium following the intravenous administration of technetium-99m methoxy isobutyl isonitrile at peak exercise. All patients also underwent three-vessel coronary angiography. The SPECT technique produced very detailed images allowing easy delineation of localized myocardial defects. Segmental myocardial uptake defects were compared with diseased vessels as shown at angiography. A good correlation was shown between right coronary artery (RCA) disease and mid and proximal inferior segments and between left circumflex (LCx) artery disease and mid and proximal lateral segments, allowing accurate localization of a defect to one of these two vessels' territories. Sensitivity and specificity of detection of disease of the RCA and LCx artery were high. Defects associated with a lesion of the left anterior descending vessel were more variable.