Search

Background Cornell voltage criteria (CL) and Sokolow-Lyon criteria (SL) for electrocardiographic left ventricular hypertrophy (ECG-LVH) are well known predictors of cardiovascular outcome. However, their predictive value may differ according to patient type and remains to be further tested in diabetic mellitus (DM) patients. Purpose The present study aims to determine the prevalence of each ECG-LVH criteria and their respective predictive value in DM patients. Method A retrospective cohort study of individuals age >40 years with digital ECGs from primary care were collected during 2001 to 2011. Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. DM was defined if individuals were prescribed oral antidiabetics or insulin, if they were diagnosed with DM type I or II, or had a HbA1c>48 mmol/l. Cox multivariable analysis was used for estimating hazard ratio (HR) and 95% confidence intervals (95% CI) for all-cause mortality during follow-up of up to 17 years. Results Included were 183,749 individuals with a digital ECG collected in primary care. A total of 13,003 (7.1%) individuals had DM, they were older (65.8 vs. 61.3 years), had more myocardial infarction (16.1% vs. 5.2%), stroke (14.4% vs. 6.2%), hypertension (35.1% vs. 13.2%), CL LVH (8.0% vs. 5.6%) and more were males (53.3% vs. 45.3%) compared to the non-DM individuals (all p0.45). Conclusion Cornell Voltage Left Ventricular Hypertrophy is a strong predictor of mortality in patients with and without diabetes and an independent risk factor compared to hypertension and diabetes. The predictive value was substantially stronger than Sokolow-Lyon Voltage criteria for hypertrophy. Figure 1. LVH and all-cause mortality Funding Acknowledgement Type of funding source: None

Background: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. Methods: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for >3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. Results: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P 2 score >2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF ( P Conclusions: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02036450 .

Aims Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels. Methods and results From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001–2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0–4.1 mmol/L and 4.2–6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.5 ms longer for each mmol/L decrease in potassium (p Restricted cubic splines on adjusted lin Conclusion The association of potassium with six commonly measured ECG parameters was non-linear. Strong associations between ECG abnormalities and potassium were seen among individuals with lower potassium levels (≤4.1 mmol/L). Acknowledgement/Funding None

Phenylketonuria (PKU) is caused by an autosomal recessive deficiency of the enzyme phelnylalanine hydroxylase leading to a failure to convert phenylalanine to tyrosine. To avoid irreversible neurological damage because of increased phenylalanine, treatment is instituted rapidly after birth. We examined 31 adult PKU patients living on a less protein-restricted diet. Theoretically, these PKU patients had an increased risk of developing vitamin B(12) and B(6) deficiency because of a limited intake of animal products. Besides laboratory tests (n = 31) we obtained clinical information (n = 30) and detailed information on food consumption (n = 28). Three-quarters of the patients had early biochemical signs of vitamin B(12) deficiency. In spite of a normal folate status, 9 (29%) had a plasma homocysteine above 12 micromol/L. In accord with these findings, the food questionnaires indicated that 11 (39%) patients received less than the recommended daily vitamin B(12), and 20 (71%) received less vitamin B(6) than recommended. A significant association was found between reduced vitamin B(12) intake and both reduced serum cobalamins (p = 0.04) and reduced serum transcobalamin saturation (p = 0.03). Eleven patients took a vitamin pill daily, and these patients had a significantly lower plasma homocysteine compared to the rest. The present study suggests that adult PKU patients were at increased risk of developing vitamin B(12) deficiency, and their intake of vitamin B(6) was below the recommended daily intake. In conclusion PKU patients need continuing dietary guidance throughout adult life, and considering the risks, costs and potential benefits, daily vitamin supplementation seems justified in these patients.

In this study, an animal model was developed for the examination of urethral strictures (US). Through a resectoscope, a resection was made in the urethras of 15 male rabbits. After 30 days, the rabbits were evaluated with urethrography, impedance planimetry and either histology or the determination of collagen content. Fifteen rabbits serving as controls were evaluated in the same way. Three rabbits in the resection group and one in the control group died before evaluation. Urethrography demonstrated a stricture in the remaining 12 animals in the resection group. The urethras of the control animals were all normal. Impedance planimetry confirmed that the luminal cross sectional area (CSA) of the strictures was significantly smaller than the CSA of the corresponding part of the urethra in the control group. No difference in CSA was found 1 cm proximal to the stricture. The strictures consisted of densely woven collagen which sent tongues into the adjacent normal parts of the urethra. No difference in collagen content was found between the two groups either at the stricture site or 1 cm proximally. The described method of producing US in the rabbit model was very consistent with all operated animals developing a stricture. The model might prove valuable in evaluating new methods for the treatment of US.

We evaluated the effect of the somatostatin analogue lanreotide on the development of surgically induced experimental strictures in the anterior urethra of the male rabbit. A total of 74 male rabbits were randomly allocated into four groups. Lanreotide was administered to the rabbits in groups 2 and 4 from day 0 to 14. To create a stricture, a resection was made in the urethra of the rabbits in groups 3 and 4 on day 2. On day 30, all rabbits were examined with urethrography, impedance planimetry and either histology or for collagen content. Urethrography and impedance planimetry demonstrated a urethral stricture in all operated animals. No difference was found between the two stricture groups, regardless of lanreotide administration, with respect to luminal cross-sectional area (CSA), circumferential tension-strain relation, histology or collagen content. The CSA of the urethra of the normal controls treated with lanreotide was smaller than the CSA of the normal controls not treated with lanreotide, however, no difference was found in histology or collagen content. Lanreotide had no measurable effect on the development of a surgically induced stricture in the male rabbit anterior urethra, however, lanreotide seems to exert an inhibitory effect on the normal growth of the urethra.

The aim of this study was to determine whether intravesical treatment with capsaicin could block detrusor hyper-reflexia (DH) and alter the substance P content, nerve fibres and mucosa of the bladder. Twelve patients with spinal cord disease with DH and urinary incontinence resistant to anticholinergic treatment underwent intravesical administration of 50 ml 2% lignocaine. followed by either 100 ml 1 mmol/l capsaicin or 100 ml physiological saline for 30 min. Cross-over to the alternative treatment took place after 4 weeks. Varying degrees of burning sensation were experienced by all but one patient during the capsaicin treatment and precluded the possibility of conducting studies of this type in a blind manner. No preference for capsaicin treatment was found, and micturition and VAS scores were unchanged after treatment with capsaicin. The mean volume of the contents of the bladder at which DH first appeared was 175 ml after saline and 195 ml after capsaicin (mean difference 20 ml with a 5% confidence interval from -25 to 65). Bladder biopsies taken 2 weeks after treatment with capsaicin showed more pronounced inflammation, superficial haemorrhage, squamous epithelial metaplasia and a more condensed bladder stroma. Immunohistochemical staining for substance P and neuronal cell adhesive molecule revealed the presence of small terminal axons and small nerve bundles in all of the biopsies. Intravesical treatment with capsaicin did not have a beneficial effect on DH or a destructive effect on nerve fibres. It did, however, produce significant reactive changes in the mucosa of the bladder.

Prolongation of inspiratory time is used to reduce lung injury in mechanical ventilation. The aim of this study was to isolate the effects of inspiratory time on airway pressure, gas exchange, and hemodynamics, while ventilatory frequency, tidal volume, and mean airway pressure were kept constant.Randomized experimental trial.Experimental laboratory of a University Department of Anesthesiology and Intensive Care.Twelve anesthetised piglets.After lavage the reference setting was pressure-controlled ventilation with a decelerating flow; I:E was 1:1, and PEEP was set to 75% of the inflection point pressure level. The I:E ratios of 1.5:1, 2.3:1, and 4:1 were applied randomly. Under open lung conditions, mean airway pressure was kept constant by reduction of external PEEP.Gas exchange, airway pressures, hemodynamics, functional residual capacity (SF6 tracer), and intrathoracic fluid volumes (double indicator dilution) were measured. Compared to the I:E of 1:1, PaCO2 was 8% lower, with I:E 2.3:1 and 4:1 (por = 0.01) while PaO2 remained unchanged. The decrease in inspiratory airway pressure with increased inspiratory time was due to the response of the pressure-regulated volume-controlled mode to an increased I:E ratio. Stroke index and right ventricular ejection fraction were depressed at higher I:E ratios (SI by 18% at 2.3:1, 20% at 4:1; RVEF by 10% at 2.3:1, 13% at 4:1; por = 0.05).Under open lung conditions with an increased I:E ratio, oxygenation remained unaffected while hemodynamics were impaired.

Previous studies have indicated that rat neurofilament protein may contain an endogenous MSH-like epitope with neuroregenerative properties. The presence of such an epitope has now been studied in nerve tissue from Xenopus laevis. Western blot analyses of sciatic nerve tissue using an assortment of sequence-specific MSH/ACTH antisera revealed the presence of two major immunoreactive protein bands of 52 and 50 kDa, which contained a mid-region MSH-like epitope. Weaker staining occurred in another protein band at 135 kDa. Immunocytochemistry revealed the immunoreactivity to reside in the axis cylinders of the nerve fibers. Other antisera, recognizing other regions of MSH/ACTH produced strong staining of Xenopus intermediate lobes, but failed to stain sciatic nerves. Thus, the proteins detected have no clear relation to either Xenopus neurofilament proteins or proopiomelanocortin.

A survey is given of literature reports on the effect of performance in offspring from 26 maternal PKU pregnancies treated prior to conception. The survey includes two women who were referred to us for genetic counselling because they had both given birth to microcephalic, mentally retarded children. The women were discovered to suffer from unrecognized maternal PKU with fasting phenylalanine concentration of 1.1-1.5 mmol/L. A strict diet was introduced prior to planned pregnancy and after some months on diet (phenylalanine concentrations less than 0.6 mmol/L) they became pregnant again. Serum phenylalanine levels were monitored weekly throughout pregnancy, and adjustments in the diet were made to keep serum phenylalanine concentration within the range of 0.18-0.42 mmol/L. The outcome of the pregnancies were healthy children who have developed normally. Their IQs are 105 and 119 at ten and four years of age, respectively and their head circumferences are normal. Our data show that the effect of preconceptional dietary treatment was children with a normal performance, contrary to their older siblings born following untreated pregnancies. These results are in agreement with the survey of ten years' promising experiences with preconceptional treatment in maternal PKU. The data may help to motivate young PKU women to accept planned pregnancies and to encourage them to return to the strict diet, which has prevented them from being retarded.

The plasma amino acid concentrations were measured in 12 neonates with phenylketonuria (PKU). Blood samples were taken when fasting and two hours after a meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. When the diet was instituted and plasma phenylalanine decreased, we observed a normalization of the postprandial response of isoleucine, leucine, tyrosine, and valine.

The plasma amino acid concentrations were measured in 10 children with phenylketonuria (PKU) on the phenylalanine-free amino acid mixture Phenyldon and 9 PKU children on the phenylalanine-free protein hydrolysate Albumaid. The blood samples were taken fasting and two hours after the meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. No differences of the concentration of phenylalanine on the two diet formulas were observed. Children on Phenyldon showed fasting and postprandial isoleucine higher than the reference intervals. Furthermore, a postprandial increase of several amino acids was observed on both diet formulas. This response was statistically significant in children on Phenyldon.

Rett syndrome (RS, MIM 312750) is an X linked dominant neurodevelopmental disorder, which has been considered to affect girls only.1 Males were thought to be aborted spontaneously or to have a different phenotype.2 The disease is caused by mutations in MECP2 , encoding a methyl-CpG binding protein MeCP2.3 MeCP2 is an abundantly expressed protein acting as a global transcription repressor.4 The protein contains two domains, the 85 amino acid methyl-CpG binding domain (MBD) and the 102 amino acid transcriptional repression domain (TRD).4,5 Furthermore, a domain in the C terminal part of the protein, facilitating DNA binding and harbouring the nuclear localising signal (NLS), has been described.6 The mutation responsible for RS has now been found in the majority of RS patients and more than 100 different mutations have been published. Although some association between phenotype and genotype has been shown, their correlation is not predictive of the clinical manifestations in the individual case.7,8 Since 1999, when mutations in MECP2 were first reported in patients with RS,3 it has been possible to analyse boys for mutations resulting in a confirmation of the diagnosis in some of the earlier reported cases.9,10 Screening of groups of patients with mental retardation of different types has further identified MECP2 mutations in males. So far, 17 cases of males with a disease causing mutation in MECP2 have been found. However, six of them were found to have Klinefelter syndrome or were mosaics for the mutation in question.8–15 The latter can roughly be divided into two groups, the severe neonatal cases, who die within the first years of life, all caused by an MECP2 mutation that in females causes classical RS,8–10 and the non-specific mental retardation type with mutations that, if …

To study the ability of different ventilatory approaches to keep the lung open.Different ventilatory patterns were applied in surfactant deficient lungs with PEEP set to achieve pre-lavage PaO2.Experimental laboratory of a University Department of Anaesthesiology and Intensive Care.15 anaesthetised piglets.One volume-controlled mode (L-IPPV201:1.5) and two pressure-controlled modes at 20 breaths per minute (bpm) and I:E ratios of 2:1 and 1.5:1 (L-PRVC202:1 and L-PRVC201.5:1), and two pressure-controlled modes at 60 bpm and I:E of 1:1 and 1:1.5 (L-PRVC601:1 and L-PRVC601:1.5) were investigated. The pressure-controlled modes were applied using "Pressure-Regulated Volume-Controlled Ventilation" (PRVC).Gas exchange, airway pressures, hemodynamics, FRC and intrathoracic fluid volumes were measured. Gas exchange was the same for all modes. FRC was 30% higher with all post-lavage settings. By reducing inspiratory time MPAW decreased from 25 cmH2O by 3 cmH2O with L-PRVC201.5:1 and L-PRVC601:1.5. End-inspiratory airway pressure was 29 cmH2O with L-PRVC201.5:1 and 40 cmH2O with L-IPPV201:1.5, while the other modes displayed intermediate values. End-inspiratory lung volume was 65 ml/kg with L-IPPV201:1.5, but it was reduced to 50 and 49 ml/kg with L-PRVC601:1 and L-PRVC601:1.5. Compliance was 16 and 18 ml/cmH2O with L-PRVC202:1 and L-PRVC201.5:1, while it was lower with L-IPPV201:1.5, L-PRVC601:1 and L-PRVC601:1.5. Oxygen delivery was maintained at pre-lavage level with L-PRVC201.5:1 (657 ml/min.m2), the other modes displayed reduced oxygen delivery compared with pre-lavage.Neither the rapid frequency modes nor the low frequency volume-controlled mode kept the surfactant deficient lungs open. Pressure-controlled inverse ratio ventilation (20 bpm) kept the lungs open at reduced end-inspiratory airway pressures and hence reduced risk of barotrauma. Reducing I:E ratio in this latter modality from 2:1 to 1.5:1 further improved oxygen delivery.

The organs associated with plasma volume expansion, i.e., the red bone marrow, the enlarged spleen, and the uteroplacental complex, are arteriovenous shunts with an interposed sinusoidal stroma able to skim off plasma-rich blood. In the spleen, plasma separation is an integral part of the hemoconcentration. In the red bone marrow, plasma skimming might provide a washout mechanism for the many newly formed erythrocytes and platelets from the sinusoids to the peripheral blood circulation. In the uteroplacental complex, skimming of plasma-rich blood is beneficial in increasing blood flow in the myometrium, kidneys, and skeletal musculature. The hypervolemic status with anemia will simulate a negative iron balance, which speeds up the absorption of iron. Thus a conceptual unit seems to exist in which rheological factors influence such functions as transport of newly formed blood cells into the circulation (in the red bone marrow), hemoconcentration (in the spleen), and iron balance during pregnancy (in the uteroplacental complex).

Objectives: To characterize different modes of pressure- or volume-controlled mechanical ventilation with respect to their short-term effects on oxygen delivery (DO2). Furthermore to investigate whether such differences are caused by differences in pulmonary gas exchange or by airway-pressure-mediated effects on the central hemodynamics.Design: After inducing severe respiratory distress in piglets by removing surfactant, 5 ventilatory modes were randomly and sequentially applied to each animal.Setting: Experimental laboratory of a university department of Anesthesiology and Intensive Care.Animals: 15 piglets after repeated bronchoalveolar lavage.Interventions: Volume-controlled intermittent positive-pressure ventilation (IPPV) with either 8 or 15 cmH2O PEEP; pressure-controlled inverse ratio ventilation (IRV); pressure-controlled high-frequency positive-pressure ventilation (HFPPV) and pressure-controlled high frequency ventilation with inspiratory pulses superimposed (combined high frequency ventilation, CHFV). The prefix (L) indicates that lavage has been performed.Measurements and results: Measurements of gas exchange, airway pressures, hemodynamics, functional residual capacity (using the SF6 method), intrathoracic fluid volumes (using a double-indicator dilution technique) and metabolism were performed during ventilatory and hemodynamic steady state. The peak inspiratory pressures (PIP) were significantly higher in the volume-controlled low frequency modes (43 cmH2O for L-IPPV-8 and L-IPPV-15) than in the pressure-controlled modes (39 cmH2O for L-IRV, 35 cmH2O for L-HFPPV and 33 cmH2O for L-CHFV, with PIP in the high-frequency modes being significantly lower than in inverse ratio ventilation). The mean airway pressure (MPAW) after lavage was highest with L-IRV (26 cmH2O). In the ventilatory modes with a PEEP>8 cmH2O PaO2 did not differ significantly and beyond this “opening threshold” MPAW did not further improve PaO2. Central hemodynamics were depressed by increasing airway pressures. This is especially true for L-IRV in which we found the highest MAPW and at the same time the lowest stroke index (74% of IPPV).Conclusions: In this model, as far as oxygenation is concerned, it does not matter in which specific way the airway pressures are produced. As far as oxygen transport is concerned, i.e. aiming at increasing DO2, we conclude that optimizing the circulatory status must take into account the circulatory influence of different modes of positive pressure ventilation.

The ability of sertindole to influence the ex vivo binding of 3H-ketanserin, 3H-prazosin and 3H-spiperone to 5-HT2 receptors, alpha 1-adrenoceptors and DA D2 receptors, respectively, in rat brain has been studied after acute treatment. Sertindole is a potent, long acting compound which readily passes the blood-brain barrier. It dose-dependently binds to all three receptors types. In line with in vivo behavioural experiments sertindole has the most pronounced effect on 5-HT2 receptors, lower effect on alpha 1-adrenoceptors and the lowest effect on striatal D2 receptors.

In 19 anesthetized piglets 3 ventilatory modes were studied after inducing pulmonary insufficiency by bronchoalveolar lavage by the method of Lachmann. The lavage model was considered suitable for reproduction of severe respiratory distress. This model was reproducible and stable with respect to alveolar collapse, decrease in static chest-lung compliance and increase in extravascular lung water. The ventilatory modes studied were volume-controlled intermittent positive-pressure ventilation (IPPV), pressure-controlled inverse ratio ventilation (IRV), and pressure-controlled high-frequency positive-pressure ventilation (HFPPV). The 3 ventilatory modes were used in random sequence for at least 30 min to produce a ventilatory steady state. Ventilation with no PEEP, permitting alveolar collapse, was interposed between each experimental mode. The ability to open collapsed alveoli, i.e. alveolar recruitment, was different. The recruitment rate for IPPV was 74%, but for IRV and HFPPV it was 95%, respectively. Although IRV provided the best PaO2, this was at the expense of high airway pressures with circulatory interference and reduced oxygen transport. In contrast to this, HFPPV provided lower airway pressures, less circulatory interference and improved oxygen transport. In the clinical setting there might be negative effects on vital organs and functions unless the ventilatory modes are continuously and cautiously adapted to the individual requirements in different phases of severe respiratory distress. Therefore, one ventilatory strategy could be to “open the airways” with IRV, but then switch to HFPPV in an attempt to maintain the airways open with lesser risk of barotrauma and with improved oxygen transport.

A randomized study of 6 ventilatory modes was made in 7 piglets with normal lungs. Using a Servo HFV 970 (prototype system) and a Servo ventilator 900 C the ventilatory modes examined were as follows: SV-20V, i.e. volume-controlled intermittent positive-pressure ventilation (IPPV); SV-20VIosc, i.e. volume-controlled ventilation (IPPV) with superimposed inspiratory oscillations; and SV-20VEf, i.e. volume-controlled ventilation (IPPV) with expiratory flush of fresh gas; HFV-60 denotes low-compressive high-frequency positive-pressure ventilation (HFPPV) and HVF-20 denotes low-compressive volume-controlled intermittent positive-pressure ventilation; and SV-20P denotes pressure-controlled intermittent positive-pressure ventilation. With all modes of ventilation a PEEP of 7.5 cm H2O was used. In the abbreviations used, the number denotes the ventilatory frequency in breaths per minute (bpm). HFV indicates that all gas was delivered via the HFV 970 unit. The ventilatory modes described above were applied randomly for at least 30 min, aiming for a normoventilatory steady state. The HFV-60 and the HFV-20 modes gave lower peak airway pressures, 12–13 cm H2O compared to approximately 17 cm H2O for the other ventilatory modes. Also the mean airway pressures were lower with the HFV modes 8–9 cm H2O compared to 11–14 cm H2O for the other modes. The gas distibution was evaluated by N2 washout and a modified lung clearance index. All modes showed N2 wash-out according to a two-compartment model. The SV-20P mode had the fastest wash-out, but the HFV-60 and HFV-20 ventilatory modes also showed a faster N2 wash-out than the others. Regarding the lung clearance index, the SV-20P, HFV-60 and HFV-20 modes showed better indices than the other modes. No relationship was found between the ventilatory mode and extravascular lung water, and there were no differences in the hemodynamic variables.

Seven phenylketonuria (PKU) patients aged 15–24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50–100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70–100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly. Four of the patients, however, performed rather poorly (RTv 120–220 ms) on unrestricted diet and improved significantly (P

We evaluated eight pregnancy tests: Tandem Icon, beta-hCG Rapid, Pregnastick (immunoenzymometric assays), Neo-Pregnosticon (direct hemagglutination), Pregnospia (sol particle immunoassay), Neo-Planotest (latex agglutination), Gravindex beta-hCG, and beta-hCG Slide Test (both latex-agglutination inhibition), all of which detect human choriogonadotropin (hCG) in urine. We investigated the limits of detection and the responses to the following substances: human lutropin, protein, and blood, and high concentrations of hCG. Using 100 patients' samples, we assessed the diagnostic specificity and sensitivity as well as the accuracy of each kit. The detection limits for Tandem Icon, beta-hCG Rapid, Neo-Pregnosticon, Pregnospia, Neo-Planotest, and Gravindex beta-hCG were as stated by the manufacturers. Only Neo-Planotest gave a false-positive result for lutropin. The three immunoenzymometric assays were not affected by protein or blood, but of these only Tandem Icon did not exhibit prozoning. The five other kits gave false-positive or false-negative results for protein and blood. Tandem Icon performed best, being quick and easy to use and without susceptibility to interfering substances.

The influence of indomethacin on the surgical stress response was evaluated in a double-blind study of 20 patients, scheduled for abdominal hysterectomy. The patients were randomly allocated to treatment with either indomethacin, 0.8 mg/kg i.v. preoperatively followed by 100 mg rectally 8-hourly for 3 days (Group I), or placebo (Group P), in both cases supplemented with nicomorphine as needed. Thiopentone was used for induction of anaesthesia, followed by nitrous oxide, enflurane, suxamethonium, and pancuronium. In both groups a significant increase in blood glucose and serum cortisol was seen postoperatively. Twenty-four hours later the values had almost returned to baseline. No differences were found between the absolute increases in the two groups. In both groups the serum concentrations of C-reactive protein, haptoglobin, and orosomucoid increased after an initial small decrease. We conclude that pathways involving prostaglandin synthesis play only a minor role in eliciting the postoperative hyperglycaemic, hypercortisolaemic, and acute phase protein response.

The penicillinases of Bacillus licheniformis, Bacillus cereus, and Staphylococcus aureus are related in structure and cellular localization to one another more closely than they are to penicillinases from Gram-negative organisms. In the latter, penicillinases are almost exclusively found in the periplasm, while the Gram-positive bacteria retain a substantial proportion as hydrophobic membrane-bound forms. We recently showed (Nielsen, J. B. K., Caulfield, M. P., and Lampen, J. O. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 3511-3515) that B. licheniformis membrane attachment was achieved through a glyceride thioether modification identical to that in several Gram-negative outer membrane proteins. We now report that the membrane penicillinases of S. aureus and B. cereus also possess the modification. We do this by demonstrating isotopic labeling of these forms of [3H]palmitate, by showing that they exhibit the same response to the antibiotic globomycin which appears to inhibit processing steps specifically involving the glyceride thioether in Escherichia coli outer membrane proteins, and lastly by isolating glyceryl cysteine sulfone, the oxidation product of the modified cysteine residue. By comparing the modification-susceptible signal sequences of Gram-positive penicillinases and of Gram-negative outer membrane proteins with those of nonmodified Gram-negative penicillinases, we describe in increased detail the structural features within the signal sequence that allow modification and cleavage resulting in membrane anchorage.

We studied the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. In a randomized, double-blind clinical trial involving 201 patients, 102 patients received twenty-five milligrams of indomethacin three times daily for the first six postoperative weeks, and the other ninety-nine patients received a placebo. One year after the operation, eighty-nine of those who had received indomethacin had no sign of heterotopic ossification, and the remaining thirteen had a grade-I lesion. In the group that had received a placebo, twenty-seven had no heterotopic ossification; twenty-four, a grade-I lesion; thirty, a grade-II lesion; and eighteen, a grade-III lesion. Significantly fewer patients who had received indomethacin had formation of heterotopic bone compared with those who had been given a placebo (chi-square test, p less than 0.0005). Only patients who had grade-III formation of heterotopic bone had a significant reduction in movement of the hip.

The influence of indomethacin on the need for postoperative analgesics was investigated in a double-blind study of 41 patients scheduled for abdominal hysterectomy. The incidence of side effects was evaluated. The patients were randomly allocated to treatment with either indomethacin, 0.8 mg/kg i.v. preoperatively, followed by 100 mg rectally 8-hourly for 3 days (Group I), or placebo (Group P), in both cases supplemented with nicomorphine as needed. Thiopentone was used for induction of anaesthesia, followed by nitrous oxide, enflurane, suxamethonium, and pancuronium. The average nicomorphine requirement during the study was 14.0 mg/24 h lower in Group I than in Group P. The pain score values were slightly lower in Group I when resting, but similar on movement. A significant increase in perioperative blood loss was found in Group I. Beginning the indomethacin treatment with a preoperative i.v. bolus seems to offer few advantages compared to a purely postoperative regime and may increase the risk of bleeding complications.

The chance coincidence of an X-linked disorder with an autosomal recessive disorder in one child is described. The child had the clinical phenotype of a mucopolysaccharidosis and the activity of iduronate sulphatase was almost absent. Furthermore, fibroblasts from a typical Hunter patient were unable to correct the patient's fibroblasts. However, three 24 h urine samples collected at 18-36 months of age showed a nearly normal excretion of acid mucopolysaccharides. The boy died in liver coma at 3 years of age. Autopsy showed cirrhosis of the liver and changes in liver tissue consistent with alpha 1-antitrypsin deficiency.