Dissociable roles for histone acetyltransferases p300 and PCAF in hippocampus and perirhinal cortex-mediated object memory.

The importance of histone acetylation for certain types of memory is now well established. However, the specific contributions of the various histone acetyltransferases to distinct memory functions remain to be determined; therefore, we employed selective histone acetyltransferase protein inhibitors and short-interference RNAs to evaluate the roles of CREB-binding protein (CBP), E1A-binding protein (p300) and p300/CBP-associated factor (PCAF) in hippocampus and perirhinal cortex (PRh)-mediated object memory. Rats were tested for short- (STM) and long-term memory (LTM) in the object-in-place task, which relies on the hippocampus and PRh for spatial memory and object identity processing, respectively. Selective inhibition of these histone acetyltransferases by small-interfering RNA and pharmacological inhibitors targeting the HAT domain produced dissociable effects. In the hippocampus, CBP or p300 inhibition impaired long-term but not short-term object memory, while inhibition of PCAF impaired memory at both delays. In PRh, HAT inhibition did not impair STM, and only CBP and PCAF inhibition disrupted LTM; p300 inhibition had no effects. Messenger RNA analyses revealed findings consistent with the pattern of behavioral effects, as all three enzymes were upregulated in the hippocampus (dentate gyrus) following learning, whereas only CBP and PCAF were upregulated in PRh. These results demonstrate, for the first time, the necessity of histone acetyltransferase activity for PRh-mediated object memory and indicate that the specific mnemonic roles of distinctive histone acetyltransferases can be dissociated according to specific brain regions and memory timeframe.

First comprehensive evaluation of the M.I.C. evaluator device compared to Etest and CLSI reference dilution methods for antimicrobial susceptibility testing of clinical strains of anaerobes and other fastidious bacterial species.

The new M.I.C. Evaluator strip uses test methodology and the recording of results that are similar to those of Etest. For this first assessment, 102 clinical strains of anaerobic bacteria from 12 genera and 155 strains from 7 genera and 8 species of fastidious bacteria were tested by M.I.C. Evaluator, Etest, and agar dilution or broth microdilution as a reference standard. Ampicillin, amoxicillin, amoxicillin-clavulanate, cefotaxime, ciprofloxacin, erythromycin, imipenem, levofloxacin, metronidazole, penicillin, and tetracycline were tested depending on the species. Agar dilution for anaerobes was performed according to CLSI document M11-A7. For the fastidious bacteria, CLSI document M45-A2 was followed. For the anaerobes, essential and categorical agreement between M.I.C. Evaluator and Etest was >90%. Compared to agar dilution, essential agreement was low for both strip tests, and many very major errors were observed for metronidazole (13 to 14%) and penicillin (8 to 9%) with isolates from the Bacteroides fragilis group and Clostridium species. For fastidious species, essential agreements for M.I.C. Evaluator and Etest plus or minus one doubling dilution were >95%. Compared to broth microdilution, essential agreements were low (40 to 90%) plus or minus one dilution and were >90% plus or minus two dilutions, with high overall category agreement (CA). Major and minor errors were within established parameters for all strains tested. The M.I.C. Evaluator strips were equivalent to Etest for anaerobes and fastidious species. These observations require further investigation to determine which methods provide the most accurate MIC for clinical utility. The further evaluation of additional M.I.C. Evaluator agents will be performed as they become available.

First comprehensive evaluation of the M.I.C. evaluator device compared to Etest and CLSI broth microdilution for MIC testing of aerobic Gram-positive and Gram-negative bacterial species.

The M.I.C. Evaluator strip (Thermo Fisher Scientific, Basingstoke, United Kingdom) uses a methodology similar to that of Etest. In this first assessment of the M.I.C. Evaluator device, 409 strains of aerobic Gram-positive bacteria (staphylococci, streptococci, and enterococci) and 325 strains of Enterobacteriaceae, Pseudomonas species, and Acinetobacter species were tested by M.I.C. Evaluator strip, Etest, and broth microdilution as a reference standard. The Gram-positive bacteria included staphylococci (methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus, and coagulase-negative staphylococci), Streptococcus pneumoniae, beta-hemolytic streptococci and viridians group strains, vancomycin-resistant enterococci, and other enterococci. The Gram-negative bacteria included 250 strains of 60 Enterobacteriaceae species plus 50 Pseudomonas and 25 Acinetobacter species. A total of 14 antimicrobial agents (depending on the species) were included. The same methodology and reading format were used for M.I.C. Evaluator strips and Etest. Broth microdilution methodology was performed according to CLSI document M07-A8. For the clinical strains, >95% of results were plus or minus one doubling dilution for all species. There were fewer than 5% minor errors, fewer than 3% major errors, and fewer than 1% very major errors. M.I.C. Evaluator strips and Etest often reported higher MICs than the reference broth microdilution method. The M.I.C. Evaluator strips provided results comparable to those of the predicate Etest device and are of value for the accurate testing of MICs for these important pathogens.

Randomised controlled trial assessing the impact of increasing information to health visitors about children's injuries.

AIMS: To assess the effect on health visitor action of providing community health visitors with information on all injury attendances in children under 5 attending an accident and emergency (A&E) department and of providing additional information about each injury. METHODS: Children under 5 years attending the A&E department at Queen's Medical Centre, Nottingham between October 1998 and April 1999 were studied, using a randomised controlled trial with a 2x2 factorial design. All attendances or selected attendances (all children under 1, burns and scalds, poisonings, head injuries, and repeat attendances in preceding six months) were notified. Provision of standard (diagnosis, circumstances surrounding injury, and disposal) or additional information (standard information plus place of injury, number of A&E attendances for injury in previous year, and any information recorded about safety equipment) was noted. RESULTS: Many notifications (56%) do not result in any action. Health visitors were nearly twice as likely to take action of some kind and three times as likely to undertake a home visit on receipt of notifications for selected attendances than on those for all attendances. A greater number of actions per notification were taken on receipt of information about selected attendances. Providing additional information had little effect on the action taken. CONCLUSIONS: A selective policy for notifying community health visitors of child injury attendances at A&E results in a greater proportion of attendances in which the health visitor takes action and in a greater number of actions per attendance being taken. The utility of notifying all injury attendances is questionable, as many do not result in any action.

Relation of fingerprints and shape of the palm to fetal growth and adult blood pressure.

OBJECTIVE: To examine how finger and palm prints are related to fetal growth and adult blood pressure. DESIGN: Follow up study of babies born around 50 years ago whose birth weight, placental weight, head circumference, and length at birth were recorded. SETTING: Preston, Lancashire. SUBJECTS: 139 men and women born in Sharoe Green Hospital in Preston during 1935-43 and still living in Lancashire. MAIN OUTCOME MEASURES: Finger and palm prints and current blood pressure. RESULTS: People who were thin at birth had more whorl patterns on their fingers. People who were short at birth in relation to their head circumference had longer hands and a narrower palmer angle. Mean systolic blood pressure was 8 mmHg higher (95% confidence interval 2 to 13; p = 0.01) in the 93 men and women with a whorl pattern on one or more fingers compared with the 46 who had no whorls. The greater the number of fingers with whorls the higher the systolic blood pressure. Whorls on the right hand were more strongly associated with higher systolic pressure than whorls on the left, mean systolic pressure rising by 2.2 mmHg (0.2 to 4.1; p = 0.03) for each additional whorl on the right hand. People with long hands and a narrow palmar angle also had higher systolic pressure. Again, these associations were stronger for the right hand. Mean systolic pressure rose by 0.49 mmHg (-0.03 to 1.01; p = 0.03) for each degree decrease in palmar angle on the right hand. CONCLUSIONS: Fingertip whorls and a narrow palmar angle are indelible markers of impaired fetal development at different stages in pregnancy. Both are associated with raised blood pressure in adult life.

Closed Küntscher nailing: a clinical review after 20 years.

A long-term study of patients treated by primary closed Küntscher nailing of fractures of the femoral shaft was carried out. Minimal reaming allowed nails of only 9.5-11 mm diameter to be used. One hundred and sixteen patients with 120 fractures treated in this way from 1959 to 1978 attended for clinical examination. Primary bony union was achieved in 98 per cent and the infection rate was less than 1 per cent. Full, unsupported weight bearing was possible at an average of 15.6 weeks. Symptoms and residual deformity were minimal. These results support the use of this technique in adults with most types of fracture of the femoral shaft.

Scanning and transmission electron microscopy of normal and PSE porcine muscle.

Structural differences between normal and pale, soft, exudative (PSE) longissimus dorsi (LD) muscle from purebred and crossbred pigs were observed using scanning and transmission electron microscopy. The effect of severe freeze-thaw contraction on the muscle samples was observed. The membranes of many different organelles (sarcoplasmic reticulum, mitochondria, sarcolemma and connective tissue) appeared markedly disrupted after cryofracture of PSE muscle with frequent breaks especially near the Z-lines. In addition, there was little definition of the M-line and H-zones in either the PSE or intermediate animals.