[Is family history dispensable?]. / Ist die Familienanamnese verzichtbar?

As an element of risk assessment in applications for life insurance, family medical history has a particular significance since given impairments can occur more frequently within families. Family history is not only genetic in nature. Depending on the impairment, it is also explained by external factors. There has been little literature on this topic so far, although the spectrum of family history-related impairments is very large, and their effect is highly dependent on the type of product. This paper presents a new method for assessing the effects of information contained in family history on claims, based on typical age patterns for German life insurance products (life, disability and long term care insurance), using the example of breast cancer and schizophrenia. This method helps life insurers to better understand what impact questions on family history during the stage of application have on the risk. Thus, the study contributes to the often discussed question on how essential questions on family history are.

Anaesthetic management of labour and caesarean delivery of a patient with hyperkalaemic periodic paralysis.

We describe a parturient with hyperkalaemic periodic paralysis who presented for induction of labour and subsequently, caesarean section. Epidural analgesia and anaesthesia were used successfully in a multidisciplinary plan aimed at avoiding a peripartum attack and providing safe delivery. Management of this rare condition is discussed along with a review of the available literature.

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule.

A large family with dominantly inherited rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia, resulting in brachydactyly was linked to COL2A1, the gene encoding proalpha1(II) collagen. Mutational analysis of the gene by exon sequencing identified a novel mutation in the C-propeptide region of the molecule. The glycine to aspartic acid change occurred in a region that is highly conserved in all fibrillar collagen molecules. The resulting phenotype does not fit easily into pre-existing subgroups of the type II collagenopathies, which includes spondyloepiphyseal dysplasia, and the Kniest, Strudwick, and Stickler dysplasias.

Prinzmetal's variant angina: hemodynamic and angiographic observations during pain.

Hemodynamic and angiographic data obtained during pain from four patients with Prinzmetal's variant angina are reported. The left ventricular pressure-time index did not increase before or during attacks of angina in three of the four patients; left ventricular systolic performance was impaired during pain in all three. In one of these three patients left ventricular pressure-volume data obtained during angina suggested a reduction in diastolic compliance; in another, pain and S-T segment elevation were present during coronary arterial spasm. The fourth patient had an increase in both arterial blood pressure and heart rate before an attack; in this patient coronary arterial spasm could not be demonstrated during the period of pain and S-T elevation. The data presented suggest that hemodynamic factors that increase the myocardial oxygen requirements are absent and that coronary arterial spasm is present in some, but not all, patients with variant angina.

Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Percentage of shortening of the echocardiographic left ventricular dimension. Its use in determining ejection fraction and stroke volume.

The percentage of shortening of the echocardiographic left ventricular dimension (% delta D) was prospectively evaluated in 42 patients without detectable asynergy during diagnostic cardiac catheterization and was found to correlate well with angiographic ejection fraction (r = 0.90). Ejection fraction was calculated as the product of % delta D X 1.7 or as % delta (D2), both formulae having similar degrees of accuracy and a better correlation with the angiographic determination than conventional formulae. Ejection fractions (angiographic and echocardiographic) of 51 percent or greater were always associated with a % delta D of 30 percent or more. In five patients the echocardiographically derived ejection fractions were normal (greater than or equal to 51 percent), while the angiographic ejection fractions were reduced; four of these patients had valvular regurgitation. End-diastolic volumes were calculated from end-diastolic echocardiographic dimensions utilizing a linear regression equation derived from correlating the end-diastolic echocardiographic dimension with the end-diastolic volume in 27 patients without valvular regurgitation (end-diastolic echocardiographic dimension ranged from 3.7 to 8.2 cm). The value for stroke volume determined as the product of calculated end-diastolic volume times ejection fraction correlated with the angiographically determined stroke volume (r = 0.88; standard error of estimate, +/- 11 ml) better than the value for stroke volume derived from conventional echocardiographic formulae.

Effects of an intravenous infusion of hydrochloric acid on renal function in sheep.

Responses to an intravenous infusion of hydrochloric acid (150 mumol/min for three days), sufficient to induce mild acidosis, were studied in eight ewes. No changes in glomerular filtration rate or renal plasma flow were detected as blood and urine pH, plasma PCO2, plasma concentrations of hydrogencarbonate and inorganic phosphate were reduced by the acid infused. Urinary excretion of hydrogencarbonate was abolished while that of inorganic phosphate was slightly increased. The quantities of hydrogencarbonate and inorganic phosphate ions filtered and reabsorbed decreased whereas the proportion of the filtrate reabsorbed remained unaltered.

The effects of bumetanide on renal function and blood composition in sheep.

Respones to bumetanide were studied in five ewes. During ADH infusion urine flow increased from less than 1-0 to approximately 11-5 cm3 min-1 within 30 min of intravenous injection of 0-02 mg kg-1 bumetanide and returned to approximately 2-0 cm3 min-1 within 3 h of dosing. The diuresis was accompanied by large increases in sodium and chloride excretion and smaller increases in potassium and free hydrogen ion excretion. Bicarbonate excretion and TCH20 were reduced. Plasma potassium and chloride concentrations decreased slightly while arterial bicarbonate pH and pCO2 slightly increased. A transient increase in GFR and RPF was followed by a small reduction in GFR. No change in CH20 was observed after bumetanide injection during water diuresis. Increasing the dose of bumetanide over the range 0-002 to 0-20 mg kg-1 resulted in more pronounced and prolonged responses. The results show that bumetanide is a potent diuretic in sheep with its main site of action on the ascending limb of Henle's loop.

Radial ray defects, renal ectopia, duodenal atresia and hydrocephalus: the extended spectrum for Fanconi anaemia.

We present two families with a striking concordance of multiple anomalies. These include duodenal and other bowel atresia, radial ray defects especially absent or vestigial thumb, renal ectopia and hydrocephalus. The presence of diagnostically raised sensitivity to mitomycin C in the first family has confirmed Fanconi anaemia. This has further increased the spectrum of abnormalities in Fanconi anaemia and highlights the importance of mitomycin C analysis if elements of this spectrum are encountered.

Evaluating the benefits and limitations of an accreditation system.

While accreditation programmes are not a quality assurance panacea, long experience has shown their benefits to substantially outweigh real or perceived negative impacts. It is argued that such systems are an essential basis for more sophisticated quality assurance programmes. Accreditation programmes also have unexpected benefits in the general management of hospitals.

Morality and bureaucracy in health and social policy.

The outgoing Director General set aside the usual biennial report approach of reviewing IHF's activities over the previous 2 years. Instead Dr. Pickering reviewed the developments in health care over the last decade, the period he has held office. He decried the emasculating role of bureaucracy in health care and the lack of morality in decision-making in social and health policy. The article is a cri de coeur' for a fundamental ethical review of the basis for health care changes.

Group purchasing--an international future? Health Industry Group Purchasing Association Expo Conference, October 9-11, 1996, Orlando, Florida, USA.

As Providers and suppliers in the U.S. health care market place have adopted a mindset more attuned to today's economic realities, they've made cost cutting a top priority-and to help them achieve that, they have turned to GPOs and the prospects they offer for control of supply costs through bulk buying. Will the purchasing world cross international boundaries and get even smaller? What benefits can be expected from group purchasing organisations developing an international network? Can the International Hospital Federation play a role?

Quality hospital care--global trends and future challenges.

This paper provides an international overview of trends and elements of quality services provision in hospitals. The factors reviewed are hospital accreditation, government quality intervention, resource review, clinical procedure standardisation, patient education, high technology, financial mechanisms, risk management and evidence based medicine as relates to quality.

Utilizing cardiovascular data bases to guide the balance of cost and quality.

Cardiovascular administrators are being asked to focus on quality, cost-efficient operations of their service lines, to market that service, to secure business through managed-care contracting and to increase direct referral volume.

Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment.

Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned to sertraline (up to 150 mg per day) (N=43) or placebo (N=46) in a double-blind 4-week trial. Baseline serum samples were profiled using the liquid chromatography electrochemical array; the output was digitized to create a 'digital map' of the entire measurable response for a particular sample. Response was defined as ≥50% reduction baseline to week 4 in the 17-item Hamilton Rating Scale for Depression total score. Models were built using the one-out method for cross-validation. Multivariate analyses showed that metabolic profiles partially separated responders and non-responders to sertraline or to placebo. For the sertraline models, the overall correct classification rate was 81% whereas it was 72% for the placebo models. Several pathways were implicated in separation of responders and non-responders on sertraline and on placebo including phenylalanine, tryptophan, purine and tocopherol. Dihydroxyphenylacetic acid, tocopherols and serotonin were common metabolites in separating responders and non-responders to both drug and placebo. Pretreatment metabotypes may predict which depressed patients will respond to acute treatment (4 weeks) with sertraline or placebo. Some pathways were informative for both treatments whereas other pathways were unique in predicting response to either sertraline or placebo. Metabolomics may inform the biochemical basis for the early efficacy of sertraline.

Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment.

Alzheimer's disease (AD) is the leading cause of dementia among the elderly population; however, knowledge about genetic risk factors involved in disease progression is limited. We conducted a genome-wide association study (GWAS) using clinical decline as measured by changes in the Clinical Dementia Rating-sum of boxes as a quantitative trait to test for single-nucleotide polymorphisms (SNPs) that were associated with the rate of progression in 822 Caucasian subjects of amnestic mild cognitive impairment (MCI). There was no significant association with disease progress for any of the recently identified disease susceptibility variants in CLU, CR1, PICALM, BIN1, EPHA1, MS4A6A, MS4A4E or CD33 following multiple testing correction. We did, however, identify multiple novel loci that reached genome-wide significance at the 0.01 level. These top variants (rs7840202 at chr8 in UBR5: P=4.27 × 10(-14); rs11637611 with a cluster of SNPs at chr15q23 close to the Tay-Sachs disease locus: P=1.07 × 10(-15); and rs12752888 at chr1: P=3.08 × 10(-11)) were also associated with a significant decline in cognition as well as the conversion of subjects with MCI to a diagnosis of AD. Taken together, these variants define approximately 16.6% of the MCI sub-population with a faster rate of decline independent of the other known disease risk factors. In addition to providing new insights into protein pathways that may be involved with the progress to AD in MCI subjects, these variants if further validated may enable the identification of a more homogeneous population of subjects at an earlier stage of disease for testing novel hypotheses and/or therapies in the clinical setting.