Obstetric outcomes in women with Turner karyotype.

CONTEXT: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. OBJECTIVE: This study compared obstetric outcome in women with TS karyotype with women in the general population. DESIGN: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. RESULTS: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. CONCLUSIONS: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls.

Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase.

BACKGROUND: This study was done to evaluate the diagnostic utility of antibodies against deamidated gliadin peptides compared to traditional markers for coeliac disease. AIM: To evaluate diagnostic utility of antibodies against deamidated gliadin peptide (DGP). METHODS: Sera from 176 adults, referred for endoscopy without previous analysis of antibodies against tissue transglutaminase (tTG) or endomysium (EmA), were retrospectively analysed by ELISAs detecting IgA/IgG antibodies against DGP or a mixture of DGP and tTG, and compared with IgA-tTG and EmA. Seventy-nine individuals were diagnosed with coeliac disease. RESULTS: Receiver operating characteristic analyses verified the manufacturers' cut-off limits except for IgA/IgG-DGP/tTG. In sera without IgA deficiency, the sensitivity was higher for IgA/IgG-DGP (0.85-0.87) compared with IgA-tTg (0.76) and EmA (0.61). All tests showed high specificity (0.95-1.00). Eighteen coeliac disease-sera were negative regarding IgA-tTG, nine of which were positive for IgA/IgG-DGP. Sera from coeliac disease-patients >70 years were more often negative for IgA-tTG (50%) and IgA/IgG-DGP (36%) than younger patients (15% and 8% respectively) (P < 0.01). Three of the four IgA-deficient patients were positive in the IgA/IgG-DGP assay. CONCLUSIONS: In this study of patients unselected regarding IgA-tTg/EmA, thus unbiased in this respect, IgA/IgG-DGP identified adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Serology is often negative in elderly patients with coeliac disease; a small bowel biopsy should therefore be performed generously before coeliac disease is excluded.

Women who gave birth to girls with Turner syndrome: maternal and neonatal characteristics.

BACKGROUND: The aim was to identify maternal risk factors in women giving birth to girls with Turner syndrome (TS) and to describe the characteristics of newborns with TS. METHODS: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register. Between 1973 and 2005, 494 children with TS were born. Maternal age, parity, height, smoking habits and neonatal characteristics; mode of delivery, gestational age, size at birth and Apgar score, were compared with women in the general population who gave birth to girls during the same period. RESULTS: More women with advanced maternal age (40+) delivered girls with TS, 3.2% when compared with 1.8% in the general population [OR 1.83, 95% confidence interval (CI) 1.09-3.08, after adjustment for year of birth]. Maternal height was inversely associated with TS pregnancies (P = 0.005). Late preterm birth occurred in newborns with TS in 10.5% when compared with 4.8% in the general population (OR 2.23; 95% CI: 1.67-2.97, after adjustment for year of birth and maternal age). Newborns with TS had birthweight less than -2SD in 17.8% and birth length less than -2SD in 21.0% when compared with 3.5 and 3.4%, in the general population (OR 6.55; 95% CI: 5.12-8.38 and OR 8.69; 95% CI: 6.89-10.97, after adjustment for year of birth and maternal age). CONCLUSION: Advanced maternal age and short stature were risk factors for giving birth to a girl with TS. More TS girls were born late preterm and were smaller for gestational age than non-TS girls in the general population.

Determination of the content and identity of lidocaine solutions with UV-visible spectroscopy and multivariate calibration.

A method is proposed for the determination of the content and identity of the active compound in pharmaceutical solutions by means of ultraviolet-visible (UV-Vis) spectroscopy, orthogonal signal correction (OSC) and multivariate calibration with soft independent modelling of class analogy (SIMCA) classification and partial least squares (PLS) regression. The content was determined with PLS regression and the identity with PLS regression and SIMCA classification. The method was tested on the local anaesthetic compound lidocaine. For the validation, external test sets of both manufactured sample solutions and samples from a stability study were used. For comparison with this new method, liquid chromatography was used as a reference method. The results show that in respect of accuracy, precision and repeatability, the new method is comparable to the reference method. The main advantage over liquid chromatography is the much shorter time of analysis and the simpler analytical procedure. An estimate of the analysis time saved with the proposed method compared with using liquid chromatography, together with practical considerations, is given.

Classification of human ovarian tumors using multivariate data analysis of polypeptide expression patterns.

Large amounts of data on quantitative gene expression are generated by procedures such as 2-DE analysis of proteins or cDNA microarrays. Quantitative molecular variation may potentially be used for the development of methods for the classification of tumors. We used here the statistical concepts of principal components analysis (PCA) and partial least square analysis (PLS) in an attempt to type ovarian tumors. Using a set of 170 polypeptides, 22 tumors were used to establish a model ("learning set") for classification into 3 groups (benign/borderline/malignant). Eighteen tumors were then used to test the model. Six of 8 carcinomas and 3 of 4 borderline tumors were correctly classified. Two of 6 benign lesions were correctly classified, 3 were classified as borderline and 1 as carcinoma. We conclude that it may be possible to classify tumors according to their constitutive protein expression profile using multivariate analysis, thus making classification by artificial intelligence a future possibility.

Rapid reversed-phase high-performance liquid chromatography method for quantitation, at high pH, of the recombinant apolipoprotein A-IMilano in Escherichia coli fermentation broth.

An automated reversed-phase high-performance liquid chromatography method for quantitative determination of recombinant apolipoprotein A-IMilano (r-Apo A-IM) in E. coli fermentation broth has been developed and evaluated. The use of a unique matrix (Poros IIR/H) makes it possible to achieve rapid separation and good resolution at high pH. The r-Apo A-IM-containing fraction is well separated from other proteins allowing a reliable quantification. The automation and high sample throughput of this method makes it very useful for routine determination of r-Apo A-IM in fermentation broth and in eluates from the various purfication steps. With suitable modifications and adaptions this method is likely to be useful for similar rapid analytical determination of recombinant proteins in complex solutions.

A multisensor array for visualizing continuous state transitions in biopharmaceutical processes using principal component analysis.

An array of sensors with varying sensitivities, a so-called multisensor array, has been used for monitoring the growth and production states of biopharmaceutical processes. The sensor array produced continuous and characteristic response patterns from the processes due to the differences of the sensors. By analysing these patterns with the multivariate method principal component analysis, the state as well as the change of state of the bioprocesses could be visualized. The sensors used in the array were well-known semiconductor and optical gas sensors and the array was connected in an on-line set-up to the bioreactor's headspace effluent. The sensor array was applied to the monitoring of two recombinant bioprocesses, the production of human growth hormone in Escherichia coli and human factor VIII in Chinese ovary hamster cells. The sensor array could clearly visualize the characteristic transitions during the main growth or production phases of these two bioprocesses.

The nuclear-encoded PsbW protein subunit of photosystem II undergoes light-induced proteolysis.

The repair of photoinhibitory damage to photosystem II involves the rapid degradation and turnover of the D1 reaction center subunit. Additional protein subunits which show a limited degradation at high light intensities are the complementary reaction center subunit, D2, and the two chlorophyll a binding proteins, CP 47 and CP 43. In this work, we provide the first evidence for light-induced degradation of a nuclear-encoded subunit of photosystem II, the recently discovered PsbW protein. This 6.1 kDa protein is predicted to have a single membrane span and was found to be closely associated with the photosystem II reaction center. The degradation of the PsbW protein was demonstrated by photoinhibitory experiments, both in vitro, using thylakoid membranes and photosystem II core particles, and in vivo using leaf discs. The PsbW protein showed almost the same rate and extent of degradation as the D1 protein, and its degradation was more pronounced compared to the D2 and CP 43 proteins. The degradation of the PsbW protein was shown to share many mechanistic similarities with the more well characterized D1 protein degradation, such as oxygen dependence, sensitivity to serine protease inhibitors, and high light triggering while the actual degradation could readily occur in total darkness. The degradation of the PsbW protein was impaired by protein phosphorylation, although this protein was not itself phosphorylated. This impairment was correlated to the phosphorylation of the D1 protein which has been shown to block its degradation during photoinhibitory conditions. It is concluded that the PsbW protein is not degraded as a direct consequence of primary photodamage but due to a general destabilization of the photosystem II complex under conditions were the D1 protein becomes degraded in the absence of a sufficient repair system. The results are discussed in terms of a requirement for coordination between degradation and protein synthesis/integration during the repair process of photodamaged photosystem II reaction centers.

A model for quality assessment in primary health care using the tracer condition technique with insulin treated diabetes as one of the tracers.

OBJECTIVE: To find a method for quality assessment in primary health care and to apply this method on a defined disease. DESIGN: General practitioners and hospital doctors worked out a programme for evaluating the quality of outpatient care of patients with insulin treated diabetes as one of five tracers. An expert committee comprising experienced general practitioners and hospital doctors compared two health centres with one outpatient medical department. Data were collected during a defined period combined with a one-year retrospective view, official statistics on medical care, and a questionnaire completed by the patients. SETTING: Two primary health care centres and one outpatient medical department in southwestern Sweden. PATIENTS: 243 insulin treated diabetic patients attending the hospital and 87 insulin treated patients attending the health centres. MAIN RESULTS: There were no difficulties for the expert panel to agree on which indicators were to be studied. The expert panel concluded that there was no difference between the quality of the two levels of care studied. CONCLUSIONS: Medical audit was a useful method for evaluating medical quality. Co-operation between hospital doctors and general practitioners was of great value for evaluation of the quality of primary health care.

Oxidation of human insulin-like growth factor I in formulation studies, II. Effects of oxygen, visible light, and phosphate on methionine oxidation in aqueous solution and evaluation of possible mechanisms.

PURPOSE: The oxidation of methionine in human Insulin-like Growth Factor I (hIGF-I) in aqueous solution was studied with respect to oxygen, visible light and sodium phosphate. METHODS: Aqueous solutions of hIGF-I were prepared with different amounts of phosphate and dissolved oxygen. The solutions were stored either in darkness or exposed to artificial visible light. The oxidized hIGF-I was quantified by RP-HPLC. A two level full factorial experimental design, with two levels of each of the three factors studied, was used. RESULTS: Oxidation was found to be positively correlated with light oxygen content and, interestingly, phosphate. The increasing effect of phosphate on the oxidation appears not to originate from metal contaminants. The influence of both oxygen and phosphate increased with time. The pH dependence of oxidation indicated the formation of a phosphorylated sulfonium ion as an oxidation intermediate. A significant interaction effect between phosphate and visible light suggested participation of radicals. CONCLUSIONS: Factorial experiments provide a valuable tool when studying complex mechanisms with interacting factors. The oxidation of methionine in hIGF-I is significantly affected by light but also by the presence of phosphate buffer.

Medical audit used for estimation of optimum level of outpatient care.

OBJECTIVE: To create a model for determining the optimum level of outpatient medical care and to determine this level. DESIGN: Expert committees were established comprising one or two hospital physicians and two general practitioners who checked medical records for all outpatient visits to doctors made by a defined population during a defined period of time. The determination of optimum level was made blindly by each member of the expert committee. SETTING AND PARTICIPANTS: The study comprised all visits to physicians during 10 weeks, in total more than 4,000, made by the people in a Swedish community, of which 2,084 were randomized. RESULTS: Total agreement between the members of the committee was initially reached for 84% of the visits and, after a common discussion between the committee members, for 99%. A general practitioner was considered to be the optimum level of care for 76% of the patients in the total series, in the upper ages (above 80) for about 85%. CONCLUSION: This method seemed suitable for determining the optimum level of care in a population and may be of value when planning for an optimum health care service. Based on the results from our study it seems reasonable to assume that general practitioners whose training corresponds to that of Swedish ones are competent to treat about 75% of all consultations.

Perfusion chromatography-a new procedure for very rapid isolation of integral photosynthetic membrane proteins.

The biochemical isolation of pure and active proteins or chlorophyll protein complexes has been crucial for elucidating the mechanism of photosynthetic energy conversion. Most of the proteins involved in this process are embedded in the photosynthetic membrane. The isolation of such hydrophobic integral membrane proteins is not trivial, and involves the use of detergents often combined with various time-consuming isolation procedures. We have applied the new procedure of perfusion chromatography for the rapid isolation of photosynthetic membrane proteins. Perfusion chromatography combines a highly reactive surface per bed volume with extremely high elution flow rates. We present an overview of this chromatographic method and show the rapid isolation of reaction centres from plant Photosystems I and II and photosynthetic purple bacteria, as well as the fractionation of the chlorophyll a/b-binding proteins of Photosystem I (LHC I). The isolation times have been drastically reduced compared to earlier approaches. The pronounced reduction in time for separation of photosynthetic complexes is convenient and permits purification of proteins in a more native state, including the maintainance of ligands and the possibility to isolate proteins trapped in intermediate metabolic or structural states.

Referral notes used as a tool for evaluating the co-operation between general practitioners and hospital physicians.

OBJECTIVE: To study what proportion of clinical visits to a general practitioner working at a Swedish health centre leads to a referral to a specialist, the adequacy of the reason for the referral, the quality of the referral notes, and the quality of the answers by the specialists to whom the patients had been referred. DESIGN: A referee committee representing the different medical specialists and the general practitioners studied all referral notes dealing with internal medicine, surgery, orthopaedics, and otorhinolaryngology during a defined period from two health centres as to adequacy of the reason for referral, the quality of the referral notes, and the quality of the answers to the referrals. SETTING AND PARTICIPANTS: Altogether 188 consecutive referral notes and 171 answers to these referrals from two Swedish health centres were evaluated. RESULTS: Of the visits to a general practitioner, 7-8% resulted in a referral to a hospital specialist, and 90% of these were answered by letter. The referee committee agreed that the vast majority of the reason for referral were adequate, and that the referral notes as well as the answers to these with few exceptions were adequately formulated. CONCLUSIONS: The referrals from primary health care to different medical specialists worked adequately, but it was concluded that it may be further improved. When evaluating the co-operation between two medical systems, it is important that the evaluation as well is made in co-operation by representatives from the two systems.

On the molecular mechanism of light-induced D1 protein degradation in photosystem II core particles.

The mechanism of D1 protein degradation was investigated during photoinhibitory illumination of isolated photosystem II core preparations. The studies revealed that a proteolytic activity resides within the photosystem II core complex. A relationship between the inhibition of D1 protein degradation and the binding of the highly specific serine protease inhibitor diisopropyl fluorophosphate to isolated complexes of photosystem II was observed, evidence that this protease is of the serine type. Using radiolabeled inhibitor, it was shown that the binding site, representing the active serine of the catalytic site, is located on a 43-kDa polypeptide, probably the chlorophyll a protein CP43. The protease is apparently active in darkness, with the initiation of breakdown being dependent on high light-induced substrate activation. The proteolysis, which has an optimum at pH 7.5, gives rise to primary degradation fragments of 23 and 16 kDa. In addition, D1 protein fragments of 14, 13, and 10 kDa were identified. Experiments with phosphate-labeled D1 protein and sequence-specific antisera showed that the 23- and 16-kDa fragments originate from the N- and C-termini, respectively, suggesting a primary cleavage of the D1 protein at the outer thylakoid surface in the region between transmembrane helices D and E.

Efficacy of enprofylline in acute airway obstruction.

The efficacy and safety of different regimens of intravenously administered enprofylline, an anti-asthma xanthine, were evaluated in a randomized open study, including 155 patients with acute exacerbation of obstructive lung disease. The regimen 2.5 mg/kg i.v. over 10 min was canceled after seven patients had been included, due to two cases of hypotensive/vasovagal reactions. The regimens 2.0 mg/kg/20 min and 2.5 mg/kg/20 min were significantly more effective with regard to bronchodilation than 2.0 mg/kg/10 min (PEF increase +35%, +30% and +17% respectively). Nausea and headache were the most common side effects (16-33% and 23-33% of the patients respectively on different regimens) with the lowest frequency on 2.0 mg/kg/20 min. Four additional hypotensive reactions occurred; one on each 2.0 mg/kg regimen and two on 2.5 mg/kg/20 min. The regimen 2.0 mg/kg20 min was found to be the most favourable with regard to efficacy and side effects. Enprofylline i.v. was found to be an effective bronchodilating treatment of acute airway obstruction but the frequency of side effects has to be considered.

Analgesic treatment in acute myocardial infarction. A double-blind comparison of ketobemidone + the spasmolytic A29 (Ketogan) and morphine.

The analgesic effect of ketobemidone hydrochloride + the spasmolytic component A29 (Ketogan) and morphine hydrochloride was compared double-blindly in patients with suspect acute myocardial infarction. The test drugs were administered i.v. in an initial dose of 0.5 ml (2.5 mg Ketogan, 5 mg morphine) followed, if necessary, by additional injections of 0.25 ml. Altogether, 309 patients participated in the trial. The total consumption of the test drugs showed that 5 mg Ketogan was equipotent with 10 mg of morphine. Treatment with Ketogan resulted in a significantly higher proportion of patients who were completely free of pain 15 and 30 min after the initial injection: 16% and 15% more, respectively, compared to morphine. Within 2 hours after the initial injection, approximately 15% of the patients in both treatment groups had reported nausea and about 7% had vomited (patients who vomited or were nauseated before treatment were not included in this analysis). The frequency of other side-effects was low, with no differences between the two treatment groups. Morphine caused a greater reduction of the systolic blood pressure than Ketogan. The effect of both drugs on pulse rate and respiration was the same.

Identification and quantification of arsenocholine and acetylarsenocholine in trace amounts in biological material by use of pyrolysis gas chromatography/mass spectrometry.

An analytical method, based on a selective extraction and pyrolysis gas chromatography/mass spectrometry assay of arsenocholine and acetylarsenocholine in aquatic organisms, is described. Characteristic fragmentation patterns were obtained from pyrolytically demethylated compounds. The molecules were rearranged in unique pathways which differed from those of corresponding nitrogen analogues. Qualitative determination of arsenocholine and acetylarsenocholine was achieved by gas chromatographic as well as mass spectrometric analysis of the thermal degradation products (trimethylarsine, dimethylvinylarsine and the demethylated arsenocholine or acetylarsenocholine). Arsenocholine and acetylarsenocholine in fish from industrially polluted water were isolated and identified. Massfragmentographic quantification of the arsenic compounds in fish was carried out by use of deuterium labelled analogues of arsenocholine and acetylarsenocholine as internal standards. The method showed a high sensitivity.

Potassium sparing by amiloride during thiazide therapy in hypertension.

Several studies have shown that 5 mg amiloride can counteract the hypokalemic effect of 50 mg hydrochlorothiazide (HCTZ). In a double-blind study of 30 subjects with mild to moderate primary hypertension, we determined whether this effect could be obtained with half the dose of amiloride (2.5 mg) in combination with 25 mg HCTZ. The effect of twice the dosage was evaluated in subjects with unsatisfactory blood pressure (BP) on the lower dose. Both 25 mg HCTZ/amiloride 2.5 mg and 25 mg HCTZ alone lowered BP. In subjects with untreated diastolic BP between 110 and 115 mm Hg, these doses were inadequate; twice the dose resulted in a greater reduction in BP. Irrespective of dosage, a potassium-sparing effect resulted from the combination of HCTZ and amiloride, with a reduction in serum potassium levels from HCTZ alone as well.