Effect of environmental stress of low pressure on tyrosine aminotransferase and phenylalanine 4-hydroxylase activities in the rat.

Tyrosine aminotransferase activity in the liver increased about fourfold after 9h, on exposure of rats to stress of low pressure. 2. The phenylalanine hydroxylase activity increased about 60% on exposure for 24h or more. 3. An environmental pressure decrease of about 0.033 MN/m2 is needed to increase the activity of tyrosine aminotransferase. 4. Adrenalectomy completely abolished the increase in activity of tyrosine aminotransferase obtained on exposure to low pressure. 5. Treatment with cycloheximide or actinomycin D prevented the increase in activity of tyrosine aminotransferase. 6. Treatment with cycloheximide at the early part of exposure to stress prevented the increase in activity of phenylalanine hydroxylase obtained after 24h.

Early post-operative mortality after major lower limb amputation: A systematic review of population and regional based studies

OBJECTIVE: Lower limb amputation is often associated with a high risk of early post-operative mortality. Mortality rates are also increasingly being put forward as a possible benchmark for surgical performance. The primary aim of this systematic review is to investigate early post-operative mortality following a major lower limb amputation in population/regional based studies, and reported factors that might influence these mortality outcomes. METHODS: Embase, PubMed, Cinahl and Psycinfo were searched for publications in any language on 30 day or in hospital mortality after major lower limb amputation in population/regional based studies. PRISMA guidelines were followed. A self developed checklist was used to assess quality and susceptibility to bias. Summary data were extracted for the percentage of the population who died; pooling of quantitative results was not possible because of methodological differences between studies. RESULTS: Of the 9,082 publications identified, results were included from 21. The percentage of the population undergoing amputation who died within 30 days ranged from 7% to 22%, the in hospital equivalent was 4-20%. Transfemoral amputation and older age were found to have a higher proportion of early post-operative mortality, compared with transtibial and younger age, respectively. Other patient factors or surgical treatment choices related to increased early post-operative mortality varied between studies. CONCLUSIONS: Early post-operative mortality rates vary from 4% to 22%. There are very limited data presented for patient related factors (age, comorbidities) that influence mortality. Even less is known about factors related to surgical treatment choices, being limited to amputation level. More information is needed to allow comparison across studies or for any benchmarking of acceptable mortality rates. Agreement is needed on key factors to be reported.

Short and long term mortality rates after a lower limb amputation

Objective To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75–84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.

Purification and Properties of l-4-Hydroxymandelate Oxidase from Pseudomonas convexa

An inducible membrane-bound l-4-hydroxymandelate oxidase (decarboxylating) from Pseudomonas convexa has been solubilized and partially purified. It catalyzes the conversion of l-4-hydroxymandelic acid to 4-hydroxybenzaldehyde in a single step with the stoichiometric consumption of O2 and liberation of CO2. The enzyme is optimally active at pH 6.6 and at 55 oC. It requires FAD and Mn2+ for its activity. The membrane-bound enzyme is more stable than the solubilized and purified enzyme. After solubilization it gradually loses its activity when kept at 5 oC which can be fully reactivated by freezing and thawing. The Km values for DL-4-hydroxymandelate and FAD are 0.44 mM and 0.038 mM respectively. The enzyme is highly specific for DL-4-hydroxymandelic acid. DL-3,4-Dihydroxymandelic acid competitively inhibited the enzyme reaction. From the Dixon plot the Ki for DL-3,4-dihydroxymandelic acid was calculated to be 1.8 × 10−4 M. The enzyme is completely inactivated by thiol compounds and not affected by thiol inhibitors. The enzyme is also inhibited by denaturing agents, heavy metal ions and by chelating agents.

Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile: Synthesis of 4-cyano-3-ethoxy-1-hydroxy-5,6,7,8-tetrahydroisoquinoline, an isomer of the abnormal product

The structure of the abnormal product 1a formed in the Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile has been further confirmed. Oxidation of the tetrahydroisoquinoline 3b using Na2Cr2O-AcOH-H2SO4 gave the keto isoquinoline 3d and the isoquinoline-1-carboxylic acid 5a. The acid chloride of 5a was condensed with diethyl ethoxymagnesiomalonate to afford after decarbethoxylation the methyl ketone 5d which on Baeyer-Villiger oxidation gave a mixture of the acetate 1g and the title compound 1b. The unambiguous synthesis of 1b confirms the structure assigned earlier to the title compound also formed during the partial hydrolysis of the diethoxy compound 1c. Condensation of 2-acetylcyclohexane-1,3-dione with malononitrile gave the quinoline derivative 4c which on ethylation yielded the ketoquinoline 4d. The present studies have confirmed that the quinoline compound 4a is also formed in the condensation of 2-acetylcyclohexanone and cyanoacetamide.

Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814)

An inducible benzoate-4-hydroxylase has been partially purified from crude extracts of the mycelial felts of Aspergillus niger. This enzyme catalyzes the transformation of benzoate to p-hydroxybenzoate with equimolar consumption of NADPH and O2. It requires tetrahydropteridine as a prosthetic group. The optimum activity was found at pH 6.2 with a Km value at 30°C of 1.6 · 10−4 M for NADPH and 1.3 · 10−4 M for benzoate. Fe2+ (iron) is required for the enzyme activity. The enzyme is stabilized by the inclusion of benzoate, EDTA and glutathione in the extracting buffer. The enzyme is specific for benzoate as substrate. Sulfhydryl group(s) are essential for enzyme activity as indicated by p-chloromercuri-benzoate and N-ethylmaleimide inactivation. Benzoate-4-hydroxylase activity is decreased in the mycelial felts of Aspergillus niger grown in the presence of higher concentrations of benzoate. Maximum activity of the enzyme was observed at 36 h after inoculation.

Ministers as strategic political leaders? : Strategic political steering after NPM reforms in Finland

This study explores strategic political steering after the New Public Management (NPM) reforms, with emphasis on the new role assigned to Government ministers in Finland. In the NPM model, politicians concentrate on broad, principal issues, while agencies have discretion within the limits set by politicians. In Finland, strategic steering was introduced with Management by Results (MBR), but the actual tools for strategic political steering have been the Government Programme, the Government Strategy Portfolio (GSP) and Frame Budgeting. This study addresses these tools as means of strategic steering conducted by the Cabinet and individual ministers within their respective ministries. The time frame of the study includes the two Lipponen Cabinets between 1995 and 2003. Interviews with fourteen ministers as well as with fourteen top officials were conducted. In addition, administrative reform documents and documents related to strategic steering tools were analysed. The empirical conclusions of the study can be summarised as follows: There were few signs of strategic political steering in the Lipponen Cabinets. Although the Government Programmes of both Cabinets introduced strategic thinking, the strategic guidelines set forth at the beginning of the Programme were not linked to the GSP or to Frame Budgeting. The GSP could be characterised as the collected strategic agendas of each ministry, while there was neither the will nor the courage among Cabinet members to prioritise the projects and to make selections. The Cabinet used Frame Budgeting mainly in the sense of spending limits, not in making strategic allocation decisions. As for the GSP at the departmental level, projects were suggested by top officials, and ministers only approved the suggested list. Frame Budgeting at the departmental level proved to be the most interesting strategic steering tool from ministers viewpoint: they actively participated in defining which issues would need extra financing. Because the chances for extra financing were minimal, ministers had an effect only on a marginal share of the budget. At the departmental level, the study shows that strategic plans were considered the domain of officials. As for strategies concerning specific substances, there was variation in the interest shown by the ministers. A few ministers emphasised the importance of strategic work and led strategy processes. In most cases, however, officials led the process while ministers offered comments on the drafts of strategy documents. The results of this study together with experiences reported in other countries and local politics show that political decision-makers have difficulty operating at the strategic level. The conclusion is that politicians do not have sufficient incentive to perform the strategic role implied by the NPM type of reforms. Overall, the empirical results of the study indicate the power of politics over management reforms.

A world of Bose particles

Editor's Note: Satyendranath Bose, known primarily as one of the co–founders of quantum statistics, died on 4 February 1974, a few weeks after a symposium in honor of his 80th birthday was held at the Saha Institute for Nuclear Physics in Calcutta. The following paper, originally prepared in that connection, reviews some of the more important developments in particle physics which followed from the fundamental insight contained in a four–page paper published by Bose exactly fifty years ago. At the request of the editors of the AJP, Professor Sudarshan has kindly consented to adapt his paper for reproduction here. We would like to thank William Blanpied for bringing this paper to our attention.

A simple method for large-scale preparation of chick embryo tRNA

A simple method for preparing bulk quantities of tRNA from chick embryo has been developed. In this method chick embryos were homogenized in a buffer of pH 4.5, followed by deproteinization with phenol. The aqueous layer was allowed to separate under gravity. The resulting aqueous layer, after two more phenol treatments, was directly passed through a DEAE-cellulose column and the tRNA eluted therefrom with 1 Image NaCl. The tRNA prepared by this method was as active as the one prepared at neutral pH.

Constituting religion after Williams: The false dichotomy of theocracy and secularism

The Williams case is a relevant segue to consider the broader issue of constitutional relations between church and state in Australia. This paper argues that the dichotomous approach of theocracy as opposed to secularism is false and actually undermines the proper operation of s 116. A theocracy would contravene s 116 as an establishment of religion, but secularism also amounts to a conflict with s 116 as prohibiting the free exercise of religion. The necessary alternative is to find a middle ground compatible with s 116, one which will not establish any single state religion but will allow the contribution of different religious perspectives in the process of policy-making. This paper briefly considers how such an approach may be implemented.

Recovery of Yeast Saccharomyces cerevisiae after Thermal Insult

All organisms have evolved mechanisms to acquire thermotolerance. A moderately high temperature activates heat shock genes and triggers thermotolerance towards otherwise lethal high temperature. The focus of this work is the recovery mechanisms ensuring survival of Saccharomyces cerevisiae yeast cells after thermal insult. Yeast cells, first preconditioned at 37˚C, can survive a short thermal insult at 48-50˚C and are able to refold heat-denatured proteins when allowed to recover at physiological temperature 24˚C. The cytoplasmic chaperone Hsp104 is required for the acquisition of thermotolerance and dissolving protein aggregates in the cytosol with the assistance of disaccharide trehalose. In the present study, Hsp104 and trehalose were shown to be required for conformational repair of heat-denatured secretory proteins in the endoplasmic reticulum. A reporter protein was first accumulated in the lumen of endoplasmic reticulum and heat-denatured by thermal insult, and then failed to be repaired to enzymatically active and secretion-competent conformation in the absence of Hsp104 or trehalose. The efficient transport of a glycoprotein CPY, accumulated in the endoplasmic reticulum, to the vacuole after thermal insult also needed the presence of Hsp104 and trehalose. However, proteins synthesized after thermal insult at physiological temperature were secreted with similar kinetics both in the absence and in the presence of Hsp104 or trehalose, demonstrating that the secretion machinery itself was functional. As both Hsp104 and trehalose are cytosolic, a cross-talk between cytosolic and luminal chaperone machineries across the endoplasmic reticulum membrane appears to take place. Global expression profiles, obtained with the DNA microarray technique, revealed that the gene expression was shut down during thermal insult and the majority of transcripts were destroyed. However, the transcripts of small cytosolic chaperones Hsp12 and Hsp26 survived. The first genes induced during recovery were related to refolding of denatured proteins and resumption of de novo protein synthesis. Transcription factors Spt3p and Med3p appeared to be essential for acquisition of full thermotolerance. The transcription factor Hac1p was found to be subject to delayed up-regulation at mRNA level and this up-regulation was diminished or delayed in the absence of Spt3p or Med3p. Consequently, production of the chaperone BiP/Kar2p, a target gene of Hac1p, was diminished and delayed in Δspt3 and Δmed3 deletion strains. The refolding of heat-denatured secretory protein CPY to a transport-competent conformation was retarded, and a heat-denatured reporter enzyme failed to be effectively reactivated in the cytoplasm of the deletion strains.

Long-term clinical outcome after liver transplantation

With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.

Induced higher-order aberrations after laser in situ keratomileusis (LASIK) performed with wavefront-guided IntraLase femtosecond laser in moderate to high astigmatism

Background Wavefront-guided Laser-assisted in situ keratomileusis (LASIK) is a widespread and effective surgical treatment for myopia and astigmatic correction but whether it induces higher-order aberrations remains controversial. The study was designed to evaluate the changes in higher-order aberrations after wavefront-guided ablation with IntraLase femtosecond laser in moderate to high astigmatism. Methods Twenty-three eyes of 15 patients with moderate to high astigmatism (mean cylinder, −3.22 ± 0.59 dioptres) aged between 19 and 35 years (mean age, 25.6 ± 4.9 years) were included in this prospective study. Subjects with cylinder ≥ 1.5 and ≤2.75 D were classified as moderate astigmatism while high astigmatism was ≥3.00 D. All patients underwent a femtosecond laser–enabled (150-kHz IntraLase iFS; Abbott Medical Optics Inc) wavefront-guided ablation. Uncorrected (UDVA), corrected (CDVA) distance visual acuity in logMAR, keratometry, central corneal thickness (CCT) and higher-order aberrations (HOAs) over a 6 mm pupil, were assessed before and 6 months, postoperatively. The relationship between postoperative change in HOA and preoperative mean spherical equivalent refraction, mean astigmatism, and postoperative CCT were tested. Results At the last follow-up, the mean UDVA was increased (P < 0.0001) but CDVA remained unchanged (P = 0.48) and no eyes lost ≥2 lines of CDVA. Mean spherical equivalent refraction was reduced (P < 0.0001) and was within ±0.50 D range in 61 % of eyes. The average corneal curvature was flatter by 4 D and CCT was reduced by 83 μm (P < 0.0001, for all), postoperatively. Coma aberrations remained unchanged (P = 0.07) while the change in trefoil (P = 0.047) postoperatively, was not clinically significant. The 4th order HOAs (spherical aberration and secondary astigmatism) and the HOA root mean square (RMS) increased from −0.18 ± 0.07 μm, 0.04 ± 0.03 μm and 0.47 ± 0.11 μm, preoperatively, to 0.33 ± 0.19 μm (P = 0.004), 0.21 ± 0.09 μm (P < 0.0001) and 0.77 ± 0.27 μm (P < 0.0001), six months postoperatively. The change in spherical aberration after the procedure increased with an increase in the degree of preoperative myopia. Conclusions Wavefront-guided IntraLASIK offers a safe and effective option for vision and visual function improvement in astigmatism. Although, reduction of HOA is possible in a few eyes, spherical-like aberrations are increased in majority of the treated eyes.

Mediastinitis after cardiac surgery

Mediastinitis as a complication after cardiac surgery is rare but disastrous increasing the hospital stay, hospital costs, morbidity and mortality. It occurs in 1-3 % of patients after median sternotomy. The purpose of this study was to find out the risk factors and also to investigate new ways to prevent mediastinitis. First, we assessed operating room air contamination monitoring by comparing the bacteriological technique with continuous particle counting in low level contamination achieved by ultra clean garment options in 66 coronary artery bypass grafting operations. Second, we examined surgical glove perforations and the changes in bacterial flora of surgeons' fingertips in 116 open-heart operations. Third, the effect of gentamicin-collagen sponge on preventing surgical site infections (SSI) was studied in randomized controlled study with 557 participants. Finally, incidence, outcome, and risk factors of mediastinitis were studied in over 10,000 patients. With the alternative garment and textile system (cotton group and clean air suit group), the air counts fell from 25 to 7 colony-forming units/m3 (P<0.01). The contamination of the sternal wound was reduced by 46% and that of the leg wound by >90%. In only 17% operations both gloves were found unpunctured. Frequency of glove perforations and bacteria counts of hands were found to increase with operation time. With local gentamicin prophylaxis slightly less SSIs (4.0 vs. 5.9%) and mediastinitis (1.1 vs. 1.9%) occurred. We identified 120/10713 cases of postoperative mediastinitis (1.1%). During the study period, the patient population grew significantly older, the proportion of women and patients with ASA score >3 increased significantly. In multivariate logistic regression analysis, the only significant predictor for mediastinitis was obesity. Continuous particle monitoring is a good intraoperative method to control the air contamination related to the theatre staff behavior during individual operation. When a glove puncture is detected, both gloves are to be changed. Before donning a new pair of gloves, the renewed disinfection of hands will help to keep their bacterial counts lower even towards the end of long operation. Gentamicin-collagen sponge may have beneficial effects on the prevention of SSI, but further research is needed. Mediastinitis is not diminishing. Larger populations at risk, for example proportions of overweight patients, reinforce the importance of surveillance and pose a challenge in focusing preventive measures.

Outcome of singleton pregnancy after assisted reproductive treatment

Singleton pregnancies achieved by means of assisted reproductive treatment (ART) are associated with increased obstetric and neonatal risks in comparison with spontaneously conceived singleton pregnancies. The impact of infertility- and treatment-related factors on these risks is not properly understood. In addition, the psychological effects of infertility and its treatment on the experience of pregnancy have scarcely been studied. Thus, the aim of the present study was to evaluate the importance of infertility- and treatment-related factors on prediction of pregnancy outcome, obstetric and neonatal risks, fear-of-childbirth and pregnancy-related anxiety. The subjects consisted of infertile women who achieved a singleton pregnancy by means of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). The control groups comprised spontaneously conceiving women with singleton gestations. Early pregnancy outcome was assessed by means of assay of serum human chorionic gonadoptrophin (hCG) in single samples. Other outcome data were collected from patient records, national Health Registers and via prospective questionnaire surveys. Viable pregnancies were associated with significantly higher serum hCG levels 12 days after embryo transfer than non-viable pregnancies. Among singleton pregnancies, aetiological subgroup, treatment type or the number of transferred embryos did not impair the predictive value of single hCG assessment. According to the register-based data, age-, parity- and socioeconomic status- adjusted risks of gestational hypertension, preterm contractions and placenta praevia were more frequent in the ART pregnancies than in the control pregnancies. Significantly higher rates of induction of delivery and Caesarean section occurred in the ART group than in the control group. The risks of preterm birth and low birth weight (LBW) were increased after ART pregnancy. Duration or aetiology of infertility, treatment type (fresh or frozen IVF or ICSI) or rank of treatment did not contribute to the risks of preterm birth or LBW. In addition, the risks of preterm birth and LBW remained elevated in spite of of the number of transferred embryos. Although mean duration of pregnancy was shorter and mean birth weight lower in the ART pregnancies than in the control pregnancies, these differences were hardly of clinical significance. Fear-of-childbirth and pregnancy-related anxiety were equally common to women conceiving by means of ART, or spontaneously. Partnership of five to ten years appeared to be protective as regards severe fear-of-childbirth, whereas long preceding infertility (≥ seven years) had the opposite effect. In conclusion, an early hCG assessment maintained its good predictive value regardless of infertility- or patient-related factors. Further, we did not recognise any infertility- or patient-related factors that would expose infertile women to increased obstetric or neonatal risks. However, a long period of infertility was associated with severe fear-of-childbirth.