Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides.

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site-directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.

Cardiovascular risk assessment in rheumatoid arthritis: impact of the EULAR recommendations on a national calibrated score risk index.

OBJECTIVES: To evaluate the impact of the application of the EULAR task force recommendations in the cardiovascular (CV) risk assessment of rheumatoid arthritis (RA) patients according to a national calibrated SCORE. METHODS: Two hundred and one consecutive RA patients seen at the rheumatology outpatient clinics of the University Hospital 'San Cecilio', Granada, Southern Spain, were studied. Information on demographic, classic CV risk factors, history of CV events and disease clinical features were obtained. Both the systematic coronary risk evaluation (SCORE) risk index and the modified SCORE (mSCORE) following the EULAR recommendations were performed. RESULTS: Based on the classic CV risk factors the mean ± standard deviation SCORE was 2.2 ± 2.6 (median 2). Twenty-two (11%) patients were above the threshold of high risk for the Spanish population. Following the EULAR recommendations 52 of the 124 patients (41.93%) initially classified as having intermediate risk were reclassified as having high CV risk. Therefore, the mean mSCORE was 3.3 ± 4 (median 3) and, due to this, 74 (36.8%) patients were above the threshold of high CV risk for the Spanish population. As expected, patients who had experienced CV events were older, had more CV risk factors and higher mSCORE than those without CV events. CONCLUSIONS: These observations support the claim that the mSCORE should be specifically adapted to the population to be assessed. However, the use of additional tools should be considered in an attempt to fully identify high-risk RA patients.

Enantioselective synthesis of Garner's aldehyde by asymmetric hydroformylation.

Both enantiomers of Garner's aldehyde (3) are prepared from the same alkene 4 by catalytic asymmetric hydroformylation.

Impact of early postnatal exposure of red blood cell transfusions on the severity of retinopathy of prematurity.

BACKGROUND: Postnatal exposure to red blood cell transfusion (RBCT) in premature infants is an important risk factor for Retinopathy of Prematurity (ROP) progression. We hypothesized that higher number and earlier timing of RBCT are associated with worse ROP severity and result in laser treatment at an earlier postmenstrual age (PMA) in very low birth weight (≤1500 g, VLBW) infants. METHODS: A retrospective medical record review of 631 VLBW infants over a 5-year period was performed. Demographic features and potential clinical risk factors including number of RBCT, ROP severity, and progression to laser treatment were collected to evaluate predictors of severe ROP. ANCOVA, pairwise post-hoc analyses, and multivariate regression were used to determine associations between frequency and timing of RBCT and ROP severity. RESULTS: Of the 456 eligible infants, 61 developed severe ROP (13%). There was significant correlation between number of RBCTs and ROP severity, adjusted for gestational age and birthweight (Adjusted R2 = 0.53; p < 0.001). Compared to infants with No/Mild and Type 2 ROP, infants with Type 1 ROP received more RBCTs, with higher number of RBCTs per week during the first month of life (mean RBCT in ROP No/Mild 5.7±0.4 vs Type 2 16.3±1.8 vs Type 1 22.4±1.5, p = 0.042). Laser-treated infants received a higher number of RBCTs than non-treated infants (mean RBCT 22.3 vs. 6.5, p < 0.001) but no correlation was observed between number of RBCTs and PMA at time of laser treatment. CONCLUSION: Higher number of RBCTs in early postnatal life of VLBW infants was associated with more severe ROP.

Synthesis of thromboxane B2 via ketalization/ring-closing metathesis.

Total synthesis of thromboxane B2 using intermolecular ketalization followed by ring-closing metathesis is reported. Other key steps include a Sharpless asymmetric epoxidation to form an oxirane on the endo face of the bicyclic acetal, epoxide opening using lithioacetonitrile, an allylic alcohol 1,3-transposition, and Mitsunobu lactonization.

Effect of color schemes and environmental sensitivity on job satisfaction and perceived performance.

Effects of interior office color and individual stimulus screening ability, i.e. instinctive perceptual filtering of irrelevant stimuli, on perceived performance and job satisfaction were examined on various outcome measures over a 4-day work week in a laboratory setting. Workers performed specific tasks and worked regular hours for 4 consecutive days in the same office. They were separated into three groups according to their ability to ignore irrelevant stimuli in the interior space. Those in the white and predominantly blue-green offices reported higher perceived job performance and satisfaction than those in the predominantly red office regardless of stimulus screening ability. Workers with high to moderate stimulus screening ability indicated greater perceived performance and job satisfaction than did workers with low stimulus screening ability. Results for color schemes are discussed in terms of preference and social expectations.

Immunomycology: rapid and specific immunocytochemical identification of fungi in formalin-fixed, paraffin-embedded material.

We report the rapid (less than 1 hr), immunocytochemical identification of various fungi in formalin-fixed, paraffin-embedded tissues using antisera originally developed for use in immunodiffusion assays. Primary antisera directed towards fungal genera including Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, and Sporothrix were examined. The specificity of each antiserum was evaluated by the presence or absence of crossreactivity with other morphologically similar fungi in both paraffin-embedded pure fungal cultures and tissues with culture-confirmed fungal infections. Each antiserum reacted strongly with the fungus to which it had been raised, whether examined in pure culture or infected tissues. The antisera raised against Candida, Cryptococcus, and Sporothrix did not exhibit cross-reactivity with any other fungus tested. However, the antisera raised to Aspergillus, Blastomyces, Coccidioides, and Histoplasma demonstrated significant crossreactivity with other genera of fungi, thus precluding their routine use in diagnostic immunocytochemistry. The results indicate that immunocytochemistry may provide an important adjunct to other methods, such as immunodiffusion or complement fixation assays and histochemical stains such as the Grocott methenamine silver or periodic acid-Schiff, when attempts are made to specifically identify certain fungi in formalin-fixed, paraffin-embedded tissues before mycology culture results are available.

Changes in 87mSr concentractions in skeletal metastases in patients responding to cyclical combination chemotherapy for advanced breast cancer.

Serial 87mSr bone scintigrams were performed on a series of patients being treated by cyclical combination chemotherapy for metastatic breast cancer. All the patients investigated responeded to the chemotherapy, but initially the scintigrams showed an apparent deterioration, in that the tumor-to-normal isotope uptake ratios increased. Following this initial "flare" the scintigram appearance improved with a decrease in the tumor-to-normal uptake ratio. It is suggested that deterioration in the scintigram in the early stages of treatment should not be regarded as an indication that the patient is failing to respond.

The pros and cons of outpatient breast biopsy.

A review of the 130 breast biopsies performed on women during the past three years at the Martin Luther King, Jr, General Hospital showed that 90 were performed on outpatients and 40 on inpatients. Of the 90 outpatient procedures, 61 were under local anesthesia and 29 under general. Only three outpatient biopsy specimens were malignant and required subsequent patient admission to the hospital for mastectomy at an interval of 9 to 14 days. In all three, the axillary nodes were uninvolved. In two, no residual tumor was found in the mastectomy specimen.

Bacteriology of the human biliary tract and the duodenum.

Using the modern anaerobic transport media and meticulous culture techniques, 74 patients undergoing biliary tract surgery were studied. The biliary system was found to be sterile in 58 patients (78%). Fifteen patients had 35 isolates of aerobic and facultative bacteria. The most common ones were Klebsiella, Enterococcus, and Escherichia coli. The only anaerobe isolated was Clostridium perfringens. Eight of 17 patients (47%) with acute cholecystitis and five of 49 patients (10%) with chronic cholecystitis, harbored bacteria in the biliary system. This study suggests that anaerobes are rare in the human biliary system; therefore, if antibiotic therapy is considered, aerobic coverage should suffice.

Exteriorized repair in the management of colon injuries.

In an attempt to reduce septic complications following colonic injury in penetrating abdominal trauma, we tested the efficacy of the exteriorized repair, also known as primary repair and exteriorization of the injured colonic segment. From June 1973 to August 1979, 50 patients with colonic injuries suitable for exteriorized repair were entered into this study. Their ages ranged from 4 to 47 years; 42 were male, eight, female. Thirty-eight had gunshot wounds, 12 had stab wounds. The majority had various associated injuries, but only five were in shock. In 33 patients (66%) the colonic wounds successfully healed and the exteriorized loop was returned into the peritoneal cavity within 14 days. In 17 patients (34%), fecal leakage developed at the repair site and the exteriorized loops were converted into colostomies without sepsis. There was no mortality and a low complication rare (18%). This method of management for selected patients has a special merit in combining the safety of exteriorization with the economy of primary repair.

Acute renal failure from complete uterine prolapse: role of polycystic kidney disease.

A 48-year-old female developed acute renal failure from obstruction caused by a complete uterine prolapse. She had polycystic kidney disease (ADPKD) with previously stable mild renal impairment. She presented with rapidly declining renal function and oliguria which reversed following manual reduction of the prolapse and insertion of a ring pessary. None of the usual risk factors for uterine prolapse were present, however ADPKD may have contributed to the prolapse. Rapid deterioration of renal function in female patients with ADPKD should prompt gynecological examination to exclude a uterine prolapse as a cause.

Role of antibiotics in penetrating abdominal trauma.

The effectiveness of antibiotics in the management of penetrating abdominal injuries was studied retrospectively in two non-controlled, non-randomized groups of patients. The uncontrolled group (107 patients) received a variety of antibiotic(s) mainly intra- and postoperatively. The protocol group (121 patients) received a combination of clindamycin and gentamicin preoperatively in the Emergency Room. The protocol group had a statistically significant reduction in the incidence of intraabdominal sepsis, 1.7% as compared to 8.3% in the uncontrolled group. Although the improved results cannot be attributed solely to the antibiotic regimen, the trend seems apparent. Therefore, to minimize septic complications in penetrating abdominal injuries, we advocate: 1. prompt resuscitation, 2. early and appropriate surgical intervention and 3. preoperative antibiotics that are effective against both the aerobic and anerobic resident flora of the gastrointestinal tract.

Shotgun wounds of the abodomen: revisited.

A review of one hundred and sixty-seven patients with penetrating abdominal injuries caused by firearms showed that 17 patients (11%) had shotgun wounds. Nine patients were treated nonoperatively, whereas eight patients had immediate exploratory laporotomy. An analysis of shotgun wounds of the abdomen is presented to outline the principles in management. Factors influencing conservative versus operative treatment are discussed. Magnitude of the clinical problems have been illustrated by means of 4 cases.

The "limiting proximal gastric pouch": the evolving solution of morbid obesity.

Seventy-five patients received the "limiting proximal gastric pouch." The technique used is the complete transverse gastric stapling with Roux-en-Y reconstruction of gastrointestinal continuity. There was one death, 13 patients required rehospitalization, and five patients required reoperation because of complications. Both the weight loss and percentage of excess weight loss were satisfactory. The patients' acceptance was very high. The limiting proximal gastric pouch is evolving as the procedure of choice for morbid obesity.

Hyperactive Children: Which Sports Have the Right Stuff?

In brief: The number of children diagnosed as hyperactive continues to grow each year. And a question often arises about whether athletic activity is appropriate for these children. Evidence strongly suggests that not only is it appropriate, but that certain sports can improve self-esteem and can make them feel less like oddities among their peers.