Forecasting health: data needs and implications for model structure. An agenda for analysing data on the health and functioning of the elderly must indicate new types of data to be collected, innovations in data collection strategies and new methods for analysis and forecasting. The required research agenda is broad and will require inputs from investigators in a number of disciplines. The data and methods required will need to be developed in order to reflect national, regional and local variations in the health phenomena under study; they will also have to be responsive to these variations. In the end, however, if the investment is to be most useful, it must be integrated into simulation and forecasting models, the mechanics of which are based on individual-level processes and not on the elements of the service system.


Resource allocation problems and health services for the elderly. The provision of appropriate health support services for the elderly has increased in importance because of the trend towards aging populations in Europe and other developed regions. Health service resource allocation models and their roles in health service systems, which are also changing to reflect changing needs for the elderly, are discussed in this article. Different types of economic and health care delivery systems are examined, particularly those leading towards decentralization, consumer participation and "deinstitutionalization". A promising resource allocation approach--the "balance-of-care" approach--is described in some detail. This and other potential approaches make it possible to identify areas which hold promise for crossnational research.


Health economic issues relevant to countries with aging populations. This article investigates the health economic impacts of aging populations, using scenario techniques and economic systems analysis. Age-related data on hospital utilization and health care expenditure are linked with demographic models for Germany from 1990 to 2040. Findings indicate that the demographic component may not play a major role in determining long-term trends as compared with other, not yet fully elucidated components of utilization and expenditure, both of which are the result of the interplay between supply and demand in health care, and of interactions with the general economy. This acts as a deterrent against the use of simple extrapolations of current indicators (or their trends), but more adequate theoretical economic models are still lacking.


Metabolism of pravastatin sodium in isolated rat hepatocytes. I. Glutathione conjugate formation reaction. 1. The metabolic fate of pravastatin sodium (sodium (+)-(3R,5R)-3,5-dihydroxy-7-((1'S,2'S,6'S,8'S,8'aR)-6'-hydroxy-2'methyl- 8'-[(S)-2"-methylbutyryloxy]-1',2',6',7',8', 8'a-hexahydro-1'-naphthyl) heptanoate) was studied in isolated rat hepatocytes. 2. Two polar metabolites were isolated and identified as a glutathione conjugate and a dihydrodiol. 3. Both metabolites were formed via an epoxide which has been identified as the 4'a beta,5' beta-epoxide on the decalin moiety. 4. Formation of the glutathione conjugate was enzymic, while the dihydrodiol was formed by non-enzymic hydrolysis of the epoxide accompanied by the intramolecular migration of the double bond.


Structural determination of the carboxylic acid metabolites of polychlorotrifluoroethylene. 1. Polychlorotrifluoroethylene (PCTFE) is a perhalogenated hydrocarbon which consists mainly of C-6 and C-8 oligomers of chlorotrifluoroethylene (CTFE) end-capped with chlorine and referred to as trimer and tetramer, respectively. PCTFE is a hydraulic fluid considered for use in advanced weapon systems. 2. Inhalation studies have shown that PCTFE causes a dose-related hepatotoxicity in rats that is accompanied by proliferation of hepatic peroxisomes and increased liver weight. 3. Carboxylic acid metabolites of PCTFE have been isolated from rats exposed to PCTFE via inhalation. These metabolites, or their formation, may be involved in the toxicity of PCTFE. 4. Trimer carboxylic acids have been isolated from rat urine and identified, and tetramer carboxylic acids have been isolated from rat liver, and identified. 5. Our investigation of trimer and tetramer carboxylic acid metabolites of PCTFE has shown that the terminal carbon bearing two chlorine atoms is the exclusive site of oxidation. No evidence was found indicating oxidation of terminal carbon atoms having one chlorine.


The effect of age on inducibility of various types of rat liver cytochrome P-450. 1. The content and specific activities of inducible cytochrome P-450 enzymes were determined in liver microsomes of rats of various ages after maximal induction with phenobarbital, isosafrole of 3-methylcholanthrene, and in untreated animals. 2. With age an increase in liver weight was observed both in untreated rats and in maximally induced ones; the microsomal protein content/g of liver decreased with age in untreated animals but not in induced ones. Total cytochrome P-450 content/mg microsomal protein remained unchanged with age in all experimental groups. 3. Immunologically detectable levels of cytochrome P4501A1/1A2 and 2B1/2B2 remain unchanged with age both in untreated animals and in maximally induced ones. 4. Several cytochrome P-450 activities showed an age-related decrease in untreated animals, but no change with age was observed in the activities of cytochrome P4501A1, 2A2 and 2B1/2B2 in rat liver microsomes. This indicates that ageing affects only the activity of some constitutive forms of cytochrome P-450 in male rats, but not the activity of inducible types of P-450. 5. Although previous results indicated decreased inducibility of the cytochrome P-450 mRNA levels with age, the present study clearly demonstrates that this is not reflected in decreased enzyme levels or activities after maximal induction. From this it is concluded that the decreased mRNA levels might rather be reflected in a decreased rate at which maximal induction can be achieved.


Effects of various medium formulations and attachment substrata on the performance of cultured ruminant hepatocytes in biotransformation studies. 1. A procedure for the isolation and primary culture of hepatocytes from goat and cattle is described. Hepatocyte culture performance was monitored for 51 h by measuring viability, cytochrome P-450 maintenance, dealkylation of scoparone and ethylmorphine, and glucuronidation of phenol red. 2. Culture medium composition is discussed in relation to differences between splanchnic blood composition of ruminant and monogastric animal species. Main differences are in glucose and volatile fatty acid concentrations. Modified Williams' E culture medium did not yield higher culture performance than non-modified Williams' E. 3. Coating of culture dishes with either collagen or fibronectin did not improve culture performance. 4. Williams' E, although developed for rodent cells, proves to be a suitable basal medium for ruminant hepatocytes. In this medium, culture quality is high for at least several days. 5. In cultured goat hepatocytes, biotransformation rate for scoparone amounted to 20 nmol/mg protein per h, for ethylmorphine 96 nmol/mg protein per h and for phenol red 2 nmol/mg protein per h. Biotransformation activity in cow hepatocytes is approximately half that in goat hepatocytes.


Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats. 1. Prediction of hepatic injury from changes in blood concentrations of caffeine (CA) and its three primary metabolites (theobromine: TB; paraxanthine: PX; theophylline; TP) after CA administration has been studied in carbon tetrachloride (CCl4)-intoxicated rats. 2. The plasma half-life (t1/2) of CA (10 mg/kg, oral) was increased, and total body clearance (CL) decreased, in CCl4-treated rats; the apparent volume of distribution (Vd) was relatively unchanged. 3. The ratios of CA to the three metabolites (TB/CA, PX/CA, TP/CA) were significantly decreased compared to those of controls. 4. There were good correlations between the ratios of TB/CA, PX/CA, and TP/CA and CL of CA (TB/CA; r = 0.944 at 1 h, r = 0.942 at 2 h: PX/CA; r = 0.974 at 1 h, r = 0.923 at 2 h: TP/CA; r = 0.866 at 1 h, r = 0.962 at 2 h). 5. Results indicate that it is possible to evaluate hepatic drug-oxidizing capacity by measuring the ratio of CA to its metabolites, using single blood sampling 1 or 2 h after CA administration in CCl4-intoxicated rats.


Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors. 1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings. Structure-pharmacokinetic relationships were studied following i.v. administration to cynomolgus monkeys. 2. The clearance (CL) of each spirosuccinimide ARI was faster (greater than 5 times) than that of the corresponding spirohydantoin compound. In both series the CL values of the C(4) methyl and methoxy analogues were 4-fold greater than those for the unsubstituted compounds, although the CL values of the methoxy and methyl derivatives in the same series were not significantly different. 3. The volumes of distribution (Vss) of the spirohydantoins were about one-half those of the corresponding spirosuccinimides, and the Vss values of the parent compounds of both ARI series did not differ dramatically from those of their methyl and methoxy analogues. 4. All six compounds were eliminated from plasma in a biexponential fashion. The half-lives (lambda 1 and lambda 2) of the spirohydantoin compounds were much longer than those of the corresponding spirosuccinimide compounds, and the unsubstituted compounds had longer half-lives than their methyl and methoxy derivatives. The longest lambda 1 and lambda 2 half-lives were observed for imirestat, while two of the spirosuccinimides had the shortest half-lives. 5. These results indicate that the relationships observed between the in vitro and in vivo activities of the six ARI can be attributed to structurally dependent differences in metabolic clearance.


Pharmacokinetics and excretion of phenol red in the channel catfish. 1. Disposition of phenol red was examined in channel catfish (Ictalurus punctatus) after oral or intravascular (i.v.) dosing at 10 mg/kg body weight. 2. Phenol red was not detectable in plasma, urine, or bile after oral administration. 3. After i.v. dosing, plasma concentrations of phenol red were best described by a two-compartment pharmacokinetic model with distribution and elimination half-lives of 2.3 and 21 min, respectively. The apparent volume of distribution at steady state (Vss) was 225 ml/kg and total body clearance (Clb) was 658 ml/h per kg. Plasma protein binding was 19%. 4. Biliary excretion was the primary route of elimination of phenol red; in 24 h, 55% of the i.v. dose was excreted in bile compared with 24% in urine. No metabolites were detected in these fluids. 5. The use of anaesthesia during dosing had no effect on the quantitative excretion of phenol red by renal or biliary routes.


Diazepam metabolism by rat and human liver in vitro: inhibition by mephenytoin. 1. Diazepam metabolism and its association with mephenytoin hydroxylase were studied in vitro using human and rat livers. 2. Enzyme kinetic parameters were obtained for the formation of p-hydroxydiazepam (p-hydroxy-DZP), N-desmethyldiazepam (NDZ), and temazepam (TMZ) from diazepam (DZP) in rat liver fractions. The Km values for formation in rat of p-hydroxy-DZP, NDZ and TMZ were 14 +/- 3 (SEM) microM, 44 +/- 4 and 63 +/- 8, respectively; clearance values calculated from Vmax/Km were 5.7, 3.2 and 4.9 ml/g per min, respectively. 3. Mephenytoin (MP) competitively inhibited, in rat liver, the formation of NDZ, but not the formation of p-hydroxy-DZP or TMZ; in human liver neither NDZ nor TMZ formation was inhibited by MP. 4. In seven different human livers the formation of p-hydroxy-DZP represented a minor pathway compared to the formation of NDZ and TMZ.


The metabolism of muzigadial by microorganisms. 1. A total of 114 microorganisms were evaluated for their ability to metabolize the antifungal drimane sesquiterpene, muzigadial. 2. Cryptococcus neoformans was found to convert muzigadial to one major metabolite, identified as a hemiacetal. 3. Streptomyces platensis produced three metabolites: the hemiacetal, its corresponding lactone, and the epoxide of the hemiacetal. 4. Streptomyces spectabilis produced the hemiacetal as well as the epoxy hemiacetal. 5. The proposed structures of all of the metabolites were based on comparisons of the spectroscopic data (1H- and 13C-n.m.r. spectra and mass spectra) between the metabolites and the parent compound. 6. Antimicrobial evaluation of the microbial metabolites indicate that metabolism decreases antifungal activity.


Pharmacokinetics of ticlopidine during chronic oral administration to healthy volunteers and its effects on antipyrine pharmacokinetics. 1. The pharmacokinetics of ticlopidine, a novel antithrombotic agent, have been investigated in 10 healthy volunteers dosed orally with the drug (250 mg 12 hourly for 21 days), to determine the basic pharmacokinetic parameters in humans, to investigate its accumulation during repeated administration, and to assess its effects on hepatic drug-metabolizing enzymes. 2. After the first dose, peak plasma concentrations (median 0.31, range 0.08-0.80 mg/l) were generally found at 2 h. The levels decreased rapidly to a median concentration of 0.087 mg/l by 4 h then declined to 0.022 (range less than 0.005-0.128) mg/l at 12 h after administration, with apparent half-lives of approx. 4 h. The median AUC value for this first dosage interval (AUC tau) was 0.97 (range 0.41-3.49) mg h l-1. 3. Pre-dose plasma concentrations indicated that steady state was reached after 5-10 days, and then remained essentially unchanged through to the end of the study. From 30 h after the final dose, drug levels declined exponentially with a median half-life of 28.8 (range less than or equal to 20-50) h. 4. Following the final dose, the median peak concentration and AUC tau were 0.99 (range 0.22-2.12) mg/l and 4.06 (range 0.90-15.2) mg h l-1 respectively. Based on AUC values, the mean accumulation factor +/- SD was 3.73 +/- 1.14. 5. The metabolic status of subjects was assessed by administration of single doses of antipyrine (700 mg orally) 7 days before the first dose of ticlopidine and 2 days after the final dose. Treatment with ticlopidine decreased antipyrine clearance, demonstrating that it inhibited drug-metabolizing enzymes. Significant correlations (r2 = 0.84, p less than 0.01) were found between the AUC values for ticlopidine and antipyrine, indicating that the interindividual variation in the pharmacokinetics of ticlopidine are explained by differences in metabolic clearance.


Effects of arsenite on hepatic mixed-function oxidase activity in rats. 1. Injection of arsenite (As3+) to control rats results in losses of total hepatic cytochrome P-450 and significant decreases of ethoxycoumarin O-deethylase (ECOD) and ethoxyresorufin O-deethylase (EROD) activities. However, As3+ appears to decrease the activity of these enzymes differentially, with EROD showing greater sensitivity than ECOD. 2. Injection of As3+ to rats treated with phenobarbital and isosafrole significantly decreases the total content of hepatic cytochrome P-450 and various mixed function oxidase (MFO) activities, with the exception of ECOD which appears to be insensitive to As3+. 3. 3-Methylcholanthrene administration apparently protects against the effects of As3+ on the cytochrome P-450 system, since total content of the cytochrome P-450 and various MFO activities were all insensitive to this treatment.


The interaction of phosphine with haemoglobin and erythrocytes. 1. Phosphine progressively converts oxyhaemoglobin to methaemoglobin and hemichrome species, with the product formed being time- and concentration-dependent. 2. The reaction of phosphine with oxyhaemoglobin leads to the formation of phosphite and phosphate. 3. Incubation of rat erythrocytes with various concentrations of phosphine results in the progressive uptake of phosphine by the erythrocytes in a temperature-dependent first-order process. 4. Uptake of phosphine by erythrocytes causes crenation, but conversion of oxyhaemoglobin to methaemoglobin and hemichrome could not be demonstrated.


Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by rat cytosolic lipoxygenase. 1. Co-oxygenation of 14C-labelled benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol was studied in rat lung cytosol, using linoleic acid as a co-substrate. Covalently bound and soluble metabolites were quantified by radiometry and h.p.l.c., respectively. 2. The co-oxygenation resulted in the production of reactive metabolites capable of protein binding as well as a series of soluble derivatives. 3. Co-oxygenation of benzo(a)pyrene yielded primarily a significant amount of benzo(a)pyrene-6,12-dione while benzo(a)pyrene-7,8-dihydrodiol led to a significant amount of benzo(a)pyrene-trans-anti-tetrol. 4. Their production was abolished by addition of 25 microM of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the linoleic acid peroxyl radicals, formed by rat lung lipoxygenase, initiate the one-electron oxidation of benzo(a)pyrene to its quinones, and epoxidation of benzo(a)pyrene-7,8-diol to the ultimate carcinogenic benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.


Hepatic mixed-function oxidases of ferret. 1. Ferret liver mixed-function oxidase enzymes have been quantified using a variety of substrates and the activities have been compared with those found in rat liver. 2. Ferret liver total cytochrome P-450 is only 30% of that of rat liver and exhibits higher 7-ethoxyresorufin O-deethylase (EROD) activity, and lower lauric acid hydroxylase activity than rat liver; other mixed-function oxidases are at similar levels of activity in both species. 3. Induction with 3-methylcholanthrene (MC), similar to MC-induction in rat, increases the total P-450 of ferret liver by 140%, but does not increase P-450 reductase or microsomal protein. EROD specific activity (pmol/min per mg protein) is increased 20-fold by MC treatment. 4. Turnover number of EROD for control liver microsomes of ferret, hamster, mouse, guinea pig and rat were 460, 69, 44, 36 and 35 pmol/min per nmol P-450, respectively, indicating the much higher value for ferret than for any of the rodent species studied. 5. Ferret liver EROD activity is inhibited by the P4501A1 inhibitor, alpha-naphthoflavone. Use of monospecific antibodies in ELISA, Western blot and enzyme-inhibition techniques has shown that EROD activity in ferret liver is attributable to two enzyme proteins orthologous with rat liver cytochromes P4501A1 and 1A2, with the former predominating. MC induces both P4501A enzyme proteins in ferret liver, as in rat liver, with P4501A1 activity predominating.


Metabolism of 2,6-dinitro[3-3H]toluene by human and rat liver microsomal and cytosolic fractions. 1. 2,6-Dinitrotoluene (2,6-DNT) metabolism by human liver and male Fischer F344 rat liver subcellular fractions under aerobic (100% oxygen) and anaerobic (100% nitrogen) incubation conditions was examined. Under aerobic conditions the major 2,6-DNT metabolite formed by hepatic microsomes was 2,6-dinitrobenzyl alcohol (2,6-DNBalc); under anaerobic conditions 2-amino-6-nitrotoluene (2Am6NT) was the major metabolite. 2. Rates of 2,6-DNBalc formation by human and rat liver microsomes under aerobic conditions were 247 and 132 pmol/min per mg protein, respectively. Rates of 2Am6NT formation by human and rat liver microsomes under anaerobic conditions were 292 and 285 pmol/min per mg protein, respectively. Anaerobic reduction of 2,6-DNT to 2Am6NT by rat and human liver microsomes was inhibited by carbon monoxide and metyrapone, which indicates that microsomal metabolism of 2,6-DNT to 2Am6NT is mediated by cytochrome P-450. 3. Liver cytosolic fractions also metabolized 2,6-DNT to 2Am6NT under anaerobic conditions. Formation of 2Am6NT by human and rat liver cytosols was supported by hypoxanthine, NADPH and NADH. Allopurinol inhibited the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by rat, but not human, liver cytosol. Dicumarol inhibited the NADPH-supported anaerobic metabolism of 2,6-DNT by human, but not rat, liver cytosol. These results indicate that xanthine oxidase contributes to the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by human liver cytosol.


A new carbamazepine metabolite in uraemic filtrate. 1. After administration of carbamazepine (Tegretal) to an epileptic patient suffering also from uraemia, a previously unknown metabolite was detected in the haemofiltrate. It was identified as the 10,11-dihydro-10-hydroxy-carbamazepine-O-beta-glucuronide. 2. Its identification was accomplished mainly by electron impact (EI), liquid secondary ion (LSI) mass spectrometry and n.m.r. spectroscopy.


Lacidipine metabolism in rat and dog: identification and synthesis of main metabolites. 1. The main metabolites of lacidipine were isolated from bile and plasma of rats and dogs following an oral dose of the 14C-labelled drug (10 mg/kg for rats: 2 and 1 mg/kg for dogs). They were identified by comparison of chromatographic and spectral data with authentic reference compounds synthesized ad hoc. 2. Five metabolites (I-V) were isolated and identified in dog bile by gradient h.p.l.c. with u.v. detection and h.p.l.c.-thermospray mass spectrometry. In all metabolites the heterocyclic ring has been oxidized to pyridine. Further biotransformation reactions involved hydroxylation of the methyl substituents and hydrolysis of the ethyl and t-butyl ester groups to produce carboxylic acids and a lactone. Some of these metabolites also occurred as glucuronide conjugates. 3. A metabolite retaining the intact dihydropyridine ring, the des-ethyl analogue of lacidipine (VI), was isolated from rat plasma where it accounted for 60% of the total circulating radioactivity up to 24 h after administration. To characterize this metabolite, h.p.l.c. with photodiode array u.v. detection also was employed. This compound was detected in dog plasma, but there was no evidence of its presence in dog bile samples. 4. Profiles of circulating metabolites were qualitatively similar in rats and dogs. Identified metabolites accounted for the large majority of total radioactivity in all the analysed samples.


Thioethers as urinary metabolites of thiophene and monobromothiophenes. 1. Thiophene and its two monobromo derivatives were administered to rats and the amounts of thioether excreted in urine were measured by an assay based on Ellman's reagent. This assay, which involves extraction and hydrolysis, was validated by determining extraction and hydrolysis efficiencies for several authentic thioethers including N-acetyl-S-(2-thienyl)-L-cysteine, a previously reported metabolite of thiophene and 2-bromothiophene. 2. The thioethers present in urine of animals dosed with thiophenes have been examined chromatographically. Contrary to previous reports, the present work indicates that S-substituted, N-acetyl-L-cysteines (mercapturic acids) are not important thioether metabolites of thiophene in rats, and the small quantity of such compounds formed does not include either of the two simple S-thienyl derivatives. 3. The two monobromo thiophenes form higher proportions of thioethers than does thiophene, and one of these thioethers, arising from 3-bromothiophene, was identified, chromatographically, as N-acetyl-S-(3-thienyl)-L-cysteine.


Lactose conjugation of sulphonamide drugs in the lactating dairy cow. 1. 14C-Sulphamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[U-14C]-sulphonamide; 220 mg/kg of body weight) was given orally or i.v. to lactating dairy cows. Milk collected from 0-48 h after dosing accounted for 2.0% (oral dose) and 1.1% (i.v. dose) of the total 14C-activity administered. 2. Sulphamethazine accounted for 70-79% (oral dose) and 54-75% (i.v. dose) of the total 14C in milk samples collected from 0-48 h after dosing. N4-acetylsulphamethazine accounted for 1-2% (oral dose) and 1-4% (i.v. dose) of the 14C in milk. 3. The major 14C-labelled metabolite in the milk was isolated and identified as the N4-lactose conjugate of sulphamethazine, a unique type of metabolite not previously reported. This metabolite accounted for 10-14% (oral dose) and 9-20% (i.v. dose) of the 14C-activity in the milk collected from 0-48 h after dosing with 14C-sulphamethazine. 4. N4-lactose conjugates of sulphapyridine, sulphamerazine, sulphathiazole, sulphadimethoxine and sulphaquinoxaline were present in the milk from cows orally dosed with these five sulphonamide drugs.


Sex difference in the excretion of zenarestat in mice, rats, dogs and humans. 1. Mice show a sex difference in the excretion of zenarestat similar to that seen in rats, but dogs and humans show no significant sex difference. 2. Female rats and mice, and both sexes of dogs and humans, appear to possess an active secretory mechanism in the renal excretion of zenarestat, which is lacking or relatively inactive in male rats and mice.


The metabolism of benzo(a)pyrene by English sole (Parophrys vetulus): comparison between isolated hepatocytes in vitro and liver in vivo. 1. Metabolites and DNA adducts of 3H-benzo(a)pyrene (BaP) formed by isolated hepatocytes from English sole (Parophrys vetulus) in vitro were compared to those in bile and liver of sole exposed i.m. to 3H-BaP. 2. English sole liver was perfused with a collagenase solution and hepatocytes were isolated with greater than 95% viability. Determination of kinetic parameters for metabolism of 3H-BaP showed a Km of 29 +/- 10 microM and an apparent Vmax of 1300 pmol BaP metabolized/10(6) cells per h. 3. Analysis of medium from hepatocyte cultures and bile by ion-pair h.p.l.c. showed significant amounts of radioactivity in regions where glucuronide and glutathione conjugates of BaP metabolites elute. No sulphate conjugates of BaP metabolites were detected. The major unconjugated metabolite formed by hepatocytes was the BaP-9,10-dihydrodiol. 4. Hydrolysis of glucuronide conjugates by beta-glucuronidase and reversed-phase h.p.l.c. analysis of chloroform-soluble metabolites showed the presence of BaP-7,8-dihydrodiol, 1-hydroxyBaP and 3-hydroxyBaP. The identities of these metabolites were confirmed by comparing their fluorescence spectra with those of standard BaP metabolites. 5. Analysis by 32P-postlabelling of the BaP-DNA adducts formed in isolated hepatocytes and liver revealed that major adducts detected are derived from the anti-7,8-dihydrodiol-9,10-epoxideBaP (anti-BaPDE) and syn-BaPDE. 6. Results show that the types of conjugated metabolites and BaP-DNA adducts formed in primary hepatocyte culture were similar to those in bile and liver of English sole exposed to BaP. Thus, isolated hepatocytes from English sole afford a reliable alternative to live fish for studies of the mechanisms of hepatic xenobiotic metabolism and DNA adduct formation in a species shown to be susceptible to induction of hepatocarcinogenesis by PAHs.


The metabolism of 14C-tazadolene succinate in the dog. 1. Beagle dogs dosed orally with 14C-tazadolene succinate excreted much of the dose in the urine (mean 63.1% in 5 days with most excreted in the first 24 h). A lesser proportion of the dose was excreted in the faeces (mean 20.7%) and again most of this was voided in the first 24 h. 2. Four metabolites were identified and quantified in the urine, namely 3-hydroxy-(M1), 4-hydroxy- (M2a), and 3-methoxy-4-hydroxy-tazadolene (M2b) and N-[2-(phenylmethylene)cyclohexyl]-beta-alanine (M3). 3. In the 24 h urine, M2a and b glucuronides accounted for 17.7% dose, unconjugated M2a and b for 11.3%, and M3 for 18.3%. Insufficient M1 was present to be quantified. The same metabolites were seen in the 24 h faeces, but at lower concn. Thus M2a and b glucuronides, M2a and b, and M3 were 3.2%, 4.9% and 3.5% dose respectively. 4. All three phenols were present in plasma as their glucuronides as well as the beta-alanine derivative. They all had the same tmax of 2 h and t1/2 lambda 1 of the order of 1 h.


The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration. 1. The pyrethroid insecticide cypermethrin was administered orally to six male volunteers as a single dose of 3.3 mg (cis: trans 1:1) and dermally to six volunteers at a dose of 31 mg/800 cm2 (cis:trans 56:44) as a soya oil-based formulation. Urine samples were collected for up to 5 days and analysed for the metabolites cis and trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCVA), 3-phenoxybenzoic acid (3PBA) and 3-(4'-hydroxyphenoxy) benzoic acid (4OH3PBA) following an acid hydrolysis procedure. 2. Following oral dosing approx. equal amounts of (cis+trans DCVA) and (3PBA+4OH3PBA) were excreted with peak excretion rates occurring between 8 and 24 h after dosing. The ratio of trans:cis DCVA was on average 2:1. Based on DCVA measurements the amount of cypermethrin absorbed was estimated to be between 27% and 57% (mean 36%) of the administered dose. 3. Peak urinary excretion rates of metabolites occurred between 12 and 36 h after dermal dosing. The amount of metabolites derived from the phenoxybenzyl moiety (3PBA+4OH3PBA) was on average 4 times greater than the amount of (cis+trans DCVA) recovered in urine. The ratio of trans:cis DCVA was, on average 1:1.2. Based on the recovery of the phenoxybenzyl metabolites it is estimated that 0.85-1.8% (mean 1.2%) of the administered cypermethrin was absorbed. 4. These studies demonstrate marked differences in the urinary metabolite profile by the two routes, and provide an improved basis for determining the extent and main route of absorption of cypermethrin under occupational exposure conditions.


A potentially new metabolic pathway: ethyl esterification of acitretin. 1. The acidic retinoid, acitretin, was esterified to etretinate (ethyl ester) by rat and human liver 12,000 g supernatant. The amount of etretinate formed was increased by adding ethanol to the rat preparation. 2. This esterification almost certainly involves enzymic catalysis, and the amounts of etretinate formed were increased by the use of fresh rat liver. 3. Co-administration of acitretin and ethanol to rats resulted in a maximum plasma concentration of etretinate at approximately 1 h after dosing. Secondary maxima were induced by administering ethanol alone at 5 and 8 h after dosing with acitretin. 4. Comparison of acitretin and etretinate concentrations in rat portal and jugular vein plasma after ethanol administration indicated that the ester was formed mainly systematically, rather than during absorption. 5. The results of our study in the rat could indicate that the presence of etretinate in plasma of some patients being treated with acitretin may result from the intake of alcohol.


Morphogenic development of the pancreas in the staged human embryo. The Carnegie stage is widely applied in the field of human embryology, and it is more logical to analyze the embryos by this stage than CR length or menstrual age. In this study, the early development of the pancreas is studied by tissue observation and reconstruction using serial sections of 33 human embryo ranging from Carnegie stages 11 to 23. The dorsal pancreas develops from the dorsal wall of the duodenum in stage 12, and the ventral pancreas from the proximal part of the cystic primordium in stage 13 or 14 as a single epithelial thickening, but in one case, as a bilateral thickening which contains some isolated spaces. The rotation of the ventral pancreas starts in stage 15, and completes in stage 17. Surrounding connective tissue differentiates in stage 18.


Effect of peripheral nerve stimulation on the dorsal horn cell activity in cats with cutaneous inflammation. There are some reports showing that an experience of long-enduring pain causes a change in the pain transmission system, suggesting a plastic nature of the nociceptive system. However, most of the studies concerning the analgesic effect of peripheral nerve stimulation dealt with normal animal or human subjects. So, the present study was undertaken to investigate the effect of peripheral nerve stimulation on the dorsal horn cell activity using a tonic pain model, which was made by producing a cutaneous inflammation. The main results are summarized as follows. 1) The evoked activity by electrical or natural stimulation as well as spontaneous activity was enhanced, and the receptive field size was also expanded by the inflammation. 2) Peripheral nerve conditioning stimulation reduced the C-response of the dorsal horn cell in the normal and inflamed group, and the degree of inhibition between the two groups showed no significant difference. 3) Inhibition of the C-response of the dorsal horn cells by peripheral conditioning stimulation was completely reversed by naloxone in the inflamed group whereas there was a partial block in the normal group.


Network analysis of Korean health insurance policy-making process. This study examines how the decision-making process evolved in Korea during the initial phases of introduction and implementation of National Health Insurance. This study analyses the official documents and interviews views made with government officials and related personnel. We used the method of network analysis and multidimensional scaling in order to demonstrate how the major participants in the decision-making process developed and changed under the contemporary political situations. In the pre-implementation stage around 1976, major concerns were concentrated around the issues of financial support for social insurance, the fee schedule and who ought to be covered first. The total number of participants of the health or health-related organization was 61, which included the President, the Minister of Health and Social Affairs, representatives of special interest groups, etc. In the actual implementation period of 1982, different issues were brought up by the major participants. The number of participants in this period declined to 44 with the deletion of 19 and with the addition of two newly formed health insurance organizations. By 1988, as the implementation reached its final decision period, disagreements were centered on progressive premium rating and the administration of National Health Insurance. The number of participants increased to 60 after the addition of 16 participants. The analysis of this paper may provide some insight for other countries which wish to establish National Health Insurance; as reference to the policy-making process, it may provide some suggestions for when to initiate and how to formulate National Health Insurance policies.


Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer? Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.


Blood gas and electrolyte changes after tourniquet application in total knee replacement surgery. The tourniquet is widely used in upper and lower extremity surgery in orthopedic practice. However, safe working guidelines for the application of the tourniquet are not clearly defined. The use of a tourniquet is an important step in performing total knee arthroplasty, and it seems plausible that mechanical damage is directly related to the height and the duration of the pressure of the tourniquet applied. Even the tourniquet pressure which is widely accepted in clinical practice, if it is applied for several hours, would permanently damage not only tissues directly under the tourniquet but also the muscles and the nerves distal to the tourniquet. The resultant ischemia to limb produces local changes including hypoxemia, acidosis and hyperkalemia. Relatively little is known about the systemic effects of tourniquet release when the patient is undergoing total knee replacement surgery under a general anesthesia. Therefore, we studied the systemic effects. The results were as follows: 1) Approximately five minutes after the tourniquet was released there was a statistically significant increase in mean heart rate.: 2) Serum potassium levels tended to increase significantly until five minutes while the serum sodium level rose significantly only one minute, and the lactate level rose significantly for only two minutes after tourniquet released; 3) PaCO2 increased for five minutes after tourniquet release and remained elevated for 30 minutes; 4) PaO2 did not change significantly two minutes after tourniquet release; 5) The mean pH dropped to 7.34 and remained low for over five minutes.


Luminal development of the eustachian tube and middle ear: murine model. The purpose of this study was to describe the luminal development of the murine eustachian tube and middle ear. Thirty specimens, aging from gestational day 11 to postnatal day 21, were investigated through the light microscopic observations. The present study also used digitizer, computer, and serially sectioned temporal bone specimens for three-dimensional reconstruction to measure the volume of the eustachian tube and middle ear cavity at different gestational and postnatal ages. The first pharyngeal pouch elongated during gestational day 12 to form the tubotympanic recess. Between gestational day 13 and 14 this tubotympanic recess extended to the middle ear area. A rapid increment in the volume of the tubotympanic recess was noted between gestational day 15 and 16. At this age, a definite division of the tubotympanic recess into the eustachian tube and middle ear cavity was observed. During the postnatal period, the maximum change of the middle ear volume was noted on postnatal day 11 when the mesenchymal tissue in the middle ear cavity disappeared completely.


Impact of clinical history on film interpretation. We performed a study to determine whether clinical history gives a positive or negative influence on X-ray film interpretation. One hundred and nine patient's radiograms, consisting of 55 normal and 54 abnormal cases (136 abnormalities), were interpreted twice by three pairs of residents in radiology and a pair of qualified radiologists, without clinical history first and with clinical history next. The interpreters recorded diagnosis and confidence level of normal or abnormal findings on a six-point scale. Analysis of receiver operating characteristic (ROC) curves showed that knowledge of clinical history improved diagnostic accuracy. Residents, especially beginners, should be advised to obtain clinical history whenever they read radiograms.


Surgical intervention in patients with aplastic anemia. Eighteen surgical procedures have been performed on 14 cases of aplastic anemia (AA). Of the 10 major surgical procedures, 7 were emergency and 3 elective. The median duration from the diagnosis of AA to major surgery was 0.5 months (3 days-47.3 months), and the median survival after surgery was 12.3 months (4 days-38 months). The hematological status of AA at the time of major surgery were 3 in partial response (PR), 2 with no response (NR) and 5 at diagnosis, respectively; and those after major surgery were 2 with complete response (CR), 2 in PR, 1 with minimal response, and 2 in NR. Three postoperative complications were sepsis, pneumonia and atelectasis encountered in 2 cases. A total of 3 deaths were caused by infection and cancers. Considering the fact that surgery may not only control complications, but offer the opportunity to give effective therapy for AA and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed if the patient's status is not terminal.


Serum interleukin-6 in Kawasaki disease. Kawasaki disease (KD) is an acute febrile illness of infancy and early childhood. In spite of extensive studies, the cause of KD is not known. Interleukin 6 (IL-6) has manyfold biological functions involved in the immune or inflammatory responses of the host to various stimuli. Here the author investigated whether IL-6 might be responsible for manifestations of KD, such as immunoglobulin hypersecretion, lymphocyte activation and systemic vasculitis. Serum IL-6 levels in KD were determined by ELISA. Usually sera from healthy children contained only negligible levels of IL-6. Serum IL-6 was markedly elevated in all patients with acute KD, which gradually decreased during the course of the disease. Serum IL-6 correlated with serum concentration of C-reactive protein and with serum soluble interleukin-2 receptor level, but did not show any correlation with peak platelet count during subacute phase of the disease. Increased serum IL-6 level did not show any relation to development of coronary aneurysms and dilatation. Further studies will be needed to examine the source and the pathogenetic roles of increased serum IL-6 in KD.


Gastric varices: diagnosis with duplex Doppler ultrasonography--a case report. The diagnosis of gastric varices may be difficult due to their anatomic location and morphology. In this abstract we describe a case of gastric varices, of which a duplex Doppler sonography was useful in the diagnosis, that was initially suggested as submucosal tumor of the stomach by barium studies and endoscopy.


Congenital self-healing reticulohistiocytosis--report of a case of the solitary type and review of the literature. A 2-month-old female infant presented with a single hemorrhagic crusted papule on the chin present since birth. No visceral involvement could be demonstrated. The lesion involuted spontaneously with scarring in 3 months. Mononuclear cells in the cutaneous infiltrate were Langerhans cells with typical Birbeck granules which positively stained with S-100 protein. This case is the solitary type of congenital self-healing reticulohistiocytosis.


[Adolescents and computers: attitude, personality and motive for interaction]. This empirical study was undertaken to clarify controversial points emanating from previous theoretical and empirical papers dealing with apparently negative consequences on the personality development of young people who have at least a causal working-acquaintance with computers. We tested 174 persons of both sexes (age: 14-18 years) with a "Computer-Attitude-Questionnaire" and the "Mehrdimensionaler Persönlichkeitstest für Jugendliche" (Schmidt, 1981; "Multidimensional-Personality-Test"). A subgroup of 63 persons who have access to and do avail themselves of computers on a regular basis (as leisure-time activity) also answered the "Computer-Motive-Questionnaire". Statistical analyses revealed that the personality test-values of young people with a positive attitude toward computers range within the test-norm. The data for these people describe them as stress resistant, emotionally stable, well-balanced, sociable, achievement-oriented, and less aggressive.


[Processing steps in perception of speech sounds]. The aim of this study is to investigate whether speech sounds--as is stated by the widely accepted theory of categorical perception of speech--can be perceived only as instances of phonetic categories, or whether physical differences between speech sounds lead to perceptual differences regardless of their phonetic categorization. Subjects listened to pairs of synthetically generated speech sounds that correspond to realizations of the syllables "ba" and "pa" in natural German, and they were instructed to decide as fast as possible whether they perceived them as belonging to the same or to different phonetic categories. For 'same'-responses reaction times become longer when the physical distance between the speech sounds is increased; for 'different'-responses reaction times become shorter with growing physical distance between the stimuli. The results show that subjects can judge speech sounds on the basis of perceptual continua, which is inconsistent with the theory of categorical perception. A mathematical model is presented that attempts to explain the results by postulating two interacting stages of processing, a psychoacoustical and a phonetic one. The model is not entirely confirmed by the data, but it seems to deserve further consideration.


[Biofeedback of slow brain potentials].

[Biofeedback of slow brain potentials]. Slow cortical potentials constitute neurophysiological indicators of cortical excitability. Behaviorally they correlate with attention and motor preparation. A system for biofeedback and self-regulation of slow cortical potentials (SCP) has been developed. The portable system allows on-line visual feedback of filtered and corrected slow brain potentials in a predetermined sequence of trials. Three different algorithms for transforming the original SCP-signal into a feedback-signal have been developed and were compared in a controlled outcome study. With the optimal feedback method subjects were able to produce cortical positivity and negativity on command after three sessions. Increases and decreases of negativity of up to 20 microV were also achieved. Therefore a simple and portable PC-based device for the clinical application of SCP-biofeedback is now available.


[Characteristics of changes of personal odor after experimental bone marrow transplantation]. In an operant conditioning paradigm 4 Balb/c inbred strain mice were conditioned to discriminate between urine samples of two other inbred strains. The purpose was to examine whether or not the known stimulus configuration during training had any effect upon the rate of recognition of other stimuli. On the basis of this procedure, we subsequently investigated the extent to which an allogeneic bone marrow transplantation interferes with the olfactory identity of an individual. For the transplants a strain was inbred which had no contact to the animals tested, a procedure used for the first time here. Furthermore, also for the first time, it was possible to demonstrate in a direct comparison, the role played by donor versus recipient characteristics on the olfactory composition of the recipients odor.


[Psychological variables and success of interpersonal coordination of motor performance tasks]. This paper examines which dispositional, cognitive and motivational variables will contribute to improved multi-person motor coordination. The study conceptually refers to a control-theoretical approach of continuous motor behavior. According to this approach interpersonal behavior should be determined by similar regulative processes as is individual behavior. Results of a laboratory study with 18 three-person groups support assumptions of this approach. Substantial effects on group performance are found for dispositional and motivational variables. Theoretical implications of the results obtained are discussed. Conclusions for applied issues are derived.


[The effect of "stress hormones" on emotional sensitivity]. Stress is associated with an increased secretion of hormones from the hypothalamus-pituitary-adrenal-axis (HPA-axis). Once released into the blood stream they induce a number of adaptive changes that may also have pertinence to brain functions, resulting, for example in alterations of mood. To provide evidence for a mediation of mood changes by stress related hormone secretion, the influences of a short-term administration of hormones of the HPA-axis on mood and activation were assessed in a total of 182 healthy men (aged between 18 and 34 years in 7 experiments). Effects of intravenously administered hormones on self-perceived mood and activation were assessed by a standardized adjective checklist (Eigenschaftswörterliste) in placebo-controlled, double-blind experiments during rest. Results indicated no effects following corticotropin releasing-hormone or cholecystokinin, but specific effects resulted after vasopressin, oxytocin, ACTH-related hormones, and cortisol. Vasopressin and oxytocin increased activation and attenuated arousal and anger, ACTH-related hormones increased sensitivity and diminished extraversion, while cortisol increased activation and concentration. It is concluded that hormones of the HPA-axis specifically affect mood and activation. The pattern of hormonal changes in mood may have adaptive functions by preparing for behavioral and cognitive coping with stress.


[Changes in spontaneous slow potentials and visually (flash) evoked potentials in response to stimuli with no performance implication]. The influence of spontaneous slow potential shifts (SPSs) on visual (flash-)evoked potentials (VEPs) was studied. Eighteen subjects received 100 flashes. The sequence of interstimulus-intervals (ISIs) was pseudo-randomized. ISI-durations were 3, 5, 7, 9 or 11 seconds. EEG was recorded from Fz, Cz, Pz and Oz with linked-mastoids as reference. EEG was EOG-corrected and VEPs were calculated for preceding positive SPSs. Averaging was done for local SPSs; VEP pairings as well as VEPs were calculated over occipital SPS-polarities. Results showed an influence of SPSs on VEP-amplitudes. Differences in amplitudes were interpreted with the 'activation-correction'-hypothesis and with the 'ceiling'-hypothesis. Negative SPSs were followed by smaller negative peaks, and positive SPSs were followed by smaller positive peak-amplitudes. Differences in latencies of N145-P300 peak-to-peak amplitudes after SPSs of different polarity were explained with the threshold-regulation hypothesis. Spectral-analysis were done for SPS-data. There were only poor effects, showing increased parietal alpha 2-power after negative SPSs.


[Modification of autoregulation of intrinsic physical processes in field-dependent subjects: a study of performance in heart rate biofeedback]. Witkin, the founder of the concept of "field dependence", assumed that there is a relationship between field dependence and body perception. However, this hypothesis was never investigated experimentally in a well-controlled study. Twenty healthy subjects learned to increase and decrease their heart rate dependent upon two discriminative stimuli. In order to increase and decrease their heart rate they received exteroceptive feedback (movements of a rocket-ship on a video screen). Each trial lasted 6 s. The distance of the rocket-ship from a certain point indicated the amount of the achieved increase or decrease. Field dependent subjects scoring higher in field dependency as measured by the Embedded Figures Test were poorer at heart rate control on feedback and transfer trials (test trials with feedback removed) than were subjects scoring low in field dependency. This result may be of therapeutic interest in the application of behavioral medicine to psychosomatic and psychiatric disorders.


[Unconscious induction of emotions and unintended change in behavior]. The problem of most mood induction procedures in psychological laboratories is located in their demand characteristics. The subjects either have to help change their mood actively, or are at best only passively aware of the induction process. To overcome the necessity of consciousness of the mood induction procedure we developed a technique based on the involuntary tendency to imitate the expression of perceived faces ("emotional infection"). Three different mood induction conditions--operationalized by means of happy, neutral, or sad pairs of faces, which had to be compared in spite of their age--were imbedded in an experiment disguised as, research in perception'. The results show mood influences only in the behavioral measures: Happy induced subjects wrote significantly faster than neutral and sad ones. In contrast, the self description data--measured via mood adjectives--showed no typical changes due to the induction condition. The subjects seemed to be unaware of the cause and the effect of their changed mood.


[Endoscopic sclerosing of esophageal varices--technique, possibilities and limits of the method]. The paper intends to give a survey of the significance of endoscopic sclerotherapy in gastro-esophageal varices. The control of an acute bleeding can be achieved in a high percentage (70-95%). However, the hospital mortality has persisted in 30% depending on early rebleeding episodes and alterations in hepatic function. Controlled trials have confirmed a lowering of rebleeding risk as well as an improved survival by repeated sclerotherapy. The effectiveness of prophylactic sclerosing before the first bleeding is uncertain because of contrary results published. A prophylactic application seems to be favourable in patients at high risk of bleeding only.


[Incidence of local complications after heart catheter studies and their imaging with intravenous digital subtraction angiography: a retro- and prospective study]. Frequency of local complications following punction of the femoral artery aimed to cardiac catheterisation has been checked with 1051 patients retrospectively as well as 300 patients prospectively. Intravenous DSA was carried out when symptoms like stenotic murmurs, pulsations, hematoma, swelling or resistance within the concerned inguinal region appeared with suspicion diagnose of pseudoaneurysm, arteriovenous fistula or any other complications of vessels. The retrospective study reviewed a rate of complications of 1.62% and the prospective study a rate of 2.7%. The study reviewed that by using of DSA-checkings during a time period of 4 up to 10 month later no rest aneurysm or AV-fistula could be proved. That means a spontaneous thrombose took place with patients without operation indication. Significant connections were found between clinical pathological findings next to the position of punction and the occurrence of local complications. The single symptoms like stenotic murmurs or large hematoma are statistically proved indications to a complication of vessel. There is no connection between findings like pseudoaneurysm or AV-fistula and small hematomas next to the punction position. The intravenous DSA has been proved as easy and proof method with a small quantity of complications for the inclusion and differentiation of local complications following punction of the artery femoral.


[Ventilation and hemodynamics as control parameters of spa treatment]. Physical endurance training as practised at spas in the active treatment of hypertension will usually result in an increase in oxygen supply reserves and will also improve haemodynamics, so that it could help in objectively identifying the success of cardiovascular treatment. For this reason we conducted a bicycle ergometer load test in recumbent position in a group of 23 male hypertensives in stages I and II (age between 25 and 58 years) before and after a treatment course at a spa of 4 to 5 weeks' duration. The measurement parameters were ECG, blood pressure, cardiac output and the ventilatory parameters tidal volume, oxygen uptake, respiratory equivalent and respiratory quotient. Significant blood pressure reductions were seen if the load did not exceed 75 watts. The treatment course had a definite influence on cardiac output at rest and under stress. The treatment course achieves reduction and largely also normalisation of the tidal volume which is otherwise higher than in healthy persons. No influence is exercised on the respiratory equivalent. Reduction of the tidal volume and of the oxygen uptake, as well as reduction of the respiratory quotient after the treatment course can be interpreted as an improvement in the economy of the cardiovascular system. The ventilatory parameters are only conditionally suitable for arriving at an objective assessment of the curative effect of the treatment course.


[Population screening on a population level in Leipzig within the scope of the Bavarian cholesterol project]. Cholesterol determinations of 15.391 inhabitants of Leipzig were carried out in November 1990 within the Bavarian Cholesterol-Screening-Project. The aim of this screening on population basis was to identify individuals with elevated blood cholesterol levels as one of the risk factors of atherosclerosis. Capillary blood cholesterol was measured by means of the Reflotron dry-chemistry system (Boehringer, Mannheim). 27% of the inhabitants of Leipzig show cholesterol levels lower than 5.2 mmol/l as recommended by the European Society of Atherosclerosis Research. Furthermore the characteristic age dependence is seen. In comparison with the town Nürnberg lower mean cholesterol values were found in Leipzig.


[Selection modalities in the history of the medical faculty of the Halle University. II. The 19th century]. Up to the 19th century a university chair was offered to a physician, surgeon or researcher at the Department of Medicine of the University of Halle mainly by means of a decree issued by the Government or state. The statutes of the Departments of Medicine of different universities were revised and updated in the 19th century, providing for a little more leeway in respect of such calls to a university, giving the universities a right to suggest to the relevant ministers as to who, in their opinion, should receive a call to the chair of professor or assistant professor. Examples taken from the history of the university of Halle, however, show that this freedom of action was rather limited and that royal or government decrees had to be carried out even if they contradicted the conceded right to nomination.


Long-term results of treatment of malignant non-Hodgkin's lymphoma of the stomach. Our experience with 66 endoscopic-bioptic diagnosed malignant non-Hodgkin's lymphomas (NHL) showed that in most of them (57 of 66 patients) a tumor stage IE or IIE was present. All 57 primary gastric lymphomas were B-cell-lymphomas arising from the mucosa-associated lymphoid tissue (MALT). After curative primary gastric resection in stage IE and IIE the 5-year survival rate was 81%, and the 5-years lymphoma-related survival rate was 88%. These results are superior to those reported in the literature. The following two points are probably of importance for improving the prognosis: early diagnosis made possible by better knowledge of the infiltrative-flat type of tumor growth (38 out of 57 patients, including 23 cases in which infiltration was limited to mucosa and submucosa = "early lymphoma"), and extensive preoperative staging. The infiltrative-flat type, which is difficult to diagnose endoscopically, usually shows low-grade malignancy on histology (76%; in early lymphoma 83%) and has an excellent prognosis when submitted to surgery. In our experience the question as to whether additional treatment by chemotherapy and/or radiotherapy improves the prognosis of NHL of the stomach remains unanswered and further studies are needed.


[The time requirement for endoscopic diagnosis and therapy: results of a multicenter study]. For evaluation of the time requirements for endoscopic diagnostic and therapeutic procedures data of 13,321 patients gathered from 155 endoscopic units were collected. Time requirements were calculated for preparation of the procedure, examination and after-care of patients and instruments. The data indicate, that time requirement is significantly influenced by the special procedure. Therefore, calculation of the time requirement of an individual unit needs exact consideration of the frequency of different procedures. Only cleaning of instruments by washing machines could be shown to reduce time requirement. Education of endoscopists was demonstrated to be time intensive. Age (exemption children) sex of patients and video-endoscopy did not effect duration of procedures.


[Gallbladder motility in diabetic patients with and without cardiovascular neuropathy]. In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients.


[Routine gastroscopy before laparoscopic cholecystectomy: evaluation of the technology in 376 patients]. We performed endoscopy of the upper digestive tract in 376 patients before elective laparoscopic cholecystectomy. Abnormalities were found in 60 (15.9%); 14 patients had peptic ulcers, 15 gastric erosions, and 11 oesophagitis. Because of endoscopic findings 30 patients were treated medically and 2 by endoscopic polypectomy. Endoscopy lead us to cancel cholecystectomy in 4 patients; in 2 the complaints have persisted. Patients with abnormal endoscopic findings showed few significant differences in 40 variables (history and symptoms) compared with patients with normal findings. The incidence of ulcers, erosions or oesophagitis in patients over 72 years of age without loss of weight was 28.6%, compared with an overall incidence of 10.6%. Endoscopy confined to this group of patients, however, would have shown only 15% of all lesions. Consequently these predictors for endoscopic abnormalities had no practical benefit. Technology assessment according to the criteria of Fineberg et al. showed a health improvement for only 2 patients (0.5%). We conclude that routine endoscopy before laparoscopic cholecystectomy is not clinically useful in patients with symptomatic gallstone disease. This is exclusively related to patients with typical gallstone symptoms according to our definition.


Sclerosing encapsulating peritonitis: differential diagnosis to peritoneal encapsulation and abdominal cocoon--a case report. A 59 year old man presented with symptoms of partial bowel obstruction. Small bowel x-ray studies did not allow to identify the nature of the intestinal process in the upper ileum. At laparotomy small bowel encapsulation with a whitish membrane was encountered. Despite partial removal of this membrane small bowel obstruction persisted and two weeks postoperatively the patient died of peritonitis and cardiac insufficiency. Autopsy findings revealed massive fibrous adhesions in the abdomen with granulomatous inflammation. The presence of foreign body giant cells and bifringent crystals were characteristic for talcum powder. The latter suggested a causal role of an appendectomy 45 years earlier. The diagnosis of sclerosing encapsulating peritonitis as established in our patient needs to be separated from peritoneal encapsulation, a congenital malformation, and abdominal cocoon, which contains histological elements of inflammation. This case report should draw attention to these entities in the differential diagnosis and surgical management of small bowel obstruction.


Splenic hematoma in acute pancreatitis. Role of coagulation disorders. Splenic hematomas are infrequent complications of acute pancreatitis. In some cases, local factors that may play a role in the pathogenesis of the hematoma (thrombosis of the splenic artery or veins, intrasplenic pseudocysts, perisplenic adhesions, enzymatic digestion) are found. In the absence of local factors, the etiology of splenic hemorrhage remains unknown. We report two cases of splenic hematoma occurring during an acute necro-hemorrhagic pancreatitis associated with renal failure that required renal replacement therapy (hemodialysis and continuous arteriovenous hemodialysis). In both cases, more than half of splenic parenchyma was affected by multiple infarctions. No local factors responsible for the splenic abnormalities were detected in either case. Thrombosis of the splenic arterial microcirculation and a coagulation disorder consistent with disseminated intravascular coagulation was detected in one patient. In the second patient, coagulation disorders secondary to either liver disease, pancreatitis and its septic complications, or extracorporeal circuit heparinization for renal replacement therapy were present. Coagulation disorders should be considered whenever a splenic hematoma is found in a patient with acute pancreatitis. Disseminated intravascular coagulation may be the etiology of a splenic hematoma in acute pancreatitis.


[Spontaneous bacterial peritonitis].

[Spontaneous bacterial peritonitis]. Patients with liver cirrhosis and ascites suffer from spontaneous bacterial peritonitis (SBP) in up to 25%. The typical clinical signs are abdominal pain with tenderness and fever. 30% have no signs of peritonitis. Then clinical worsening, encephalopathy, rising serum creatinine levels, and therapy resistant ascites may be the only clinical features. SBP must be differentiated from bacterascites and culture negative neutrocytic ascites by the polymorphonuclear neutrophil (PMN) count in the ascites and the presence of positive culture results, which has prognostic implications. Gram negative rods from the colon play an important etiological role in SBP. Gastrointestinal bleeding, lack of serum complement, a low ascites protein and the extent of intrahepatic shunts predispose to SBP. Then, prophylaxis with the comparable drugs neomycin and norfloxacin is indicated. Coexisting encephalopathy has to be treated by the therefore effective neomycin. Otherwise, norfloxacin is the drug of choice because of better acceptance and lower costs. Chemical parameters of the ascites (pH value less than 7.4; LDH and lactate greater than serum levels; glucose less than 50 mg%) help to assess the severity of peritonitis. The course of ascitic PMN under therapy and the time of persisting positive cultures can discriminate SBP from secondary peritonitis. Antibiotics of choice are amoxicillin-clavulanic acid and cefotaxime. Short course therapy (5 days) is a effective as long course therapy (10 days). Today SBP is no more life-threatening because diagnosis, prophylaxis and therapy have improved. However, complication rate of patients with liver cirrhosis and ascites has not changed.


[Formal decision aids in gastroenterology--results of a survey]. Formal decision aids such as scores, decision-trees and expert systems, are recommended for supporting research and daily clinical work. In the field for gastroenterology it is unknown, to which degree these tools are accepted and applied in clinical routine. We therefore conducted a mail survey in order to find out whether clinical gastroenterologists know, use or want formal decision-aids. To all clinical members of a german gastroenterological scientific society (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, n = 584) an information leaflet and a questionnaire was sent. The form contained questions about use, knowledge and requests with respect to decision-aids in gastroenterology and concerning the attitude to computerized decision-aids in general. 584 clinicians received the questionnaire, 215 sent it back for analysis (39%). Formal decision-aids were used by half of the survey participants (56%), mainly three scores (Child-Pugh, Best and other indices for inflammatory bowel disease, Ranson) and four classifications (TNM, Forrest, Savary-Miller, Paquet). Computer-based formal decision-aids (e.g. expert systems) were used by a minority. Clinicians, who applied formal decision-aids stated more frequently a request for further decision-aids (72%) than those who did not (46%). A considerable part of the survey participants believed that computerized decision-aids will come into clinical routine (52%) and will improve education (37%) and clinical practice (35%). 88% were convinced, that decision-aids should be tested in controlled clinical trials before a clinical use can be recommended. There is a discrepancy between propagation of formal decision-aids and it's clinical use. Only a few scores and classifications are used in clinical routine.(ABSTRACT TRUNCATED AT 250 WORDS)


[What factors modify the condition of the newborn infant in emergency cesarean section?]. Based on 207 emergency caesarean sections carries out in 66 maternity units in North Rhine Westphalia, the condition of the newborns (pH, UA and Apgar-index after 1 minute) was examined focusing the dependence of these variables from the time management (5 time factors were analysed). Rank-correlation coefficients according to SPEARMAN were calculated and a stepwise multiple regression analysis was performed. We found a significant (P less than 0.005) positive correlation on the one hand between the preparation time for the caesarean-section (time 1) and the actual pH (UA) and on the other hand between the total time (decision to perform a caesarean section up to the delivery of the baby (time 3)) and the actual pH, UA. No significant correlation was found between the time-factors and the Apgar-index (1 min). As the correlations are positive, this means that very low pH values are associated with short time intervals and high pH values with longer time intervals respectively. We concluded, that in case of an emergency caesarean section the urgency of the emergency itself controls and determines the time management. The spatial situation in each hospital which is reflected in the time factors 4 and 5 seems to be of less important for the overall result.


Quality of life in long-term survivors of orthotopic heart transplantation. This study was designed to evaluate quality of life and life changes after heart transplantation in long-term survivors, to compare the patients' results with those obtained from healthy subjects of similar age, and to correlate quality of life with psychological and clinical variables. Questionnaires were mailed to all 43 adult German-speaking transplant patients operated between 1982 and 1986. Forty-one (95%) of this patient population completed the questionnaires; 52 controls answered those questions not addressing transplant-specific issues. 83% of the transplant patients versus 88% of the controls rated global quality of life as "good" or "excellent". Psychological affect and well-being were comparable in both groups. 70% of the transplant patients versus only 30% of the controls stated "to be bothered by symptoms". Despite that response, heart transplant recipients perceived postoperative life changes mostly as positive, although sexual function and professional situation had worsened in 34% and 41%, respectively. Global quality of life correlated best with job satisfaction (r = 0.65, p less than 0.01), satisfaction about health (r = 0.64, p less than 0.01), well being (r = 0.53, p less than 0.01), and everyday life function (r = 0.53, p less than 0.01), and correlated negatively with depression (r = -0.40) and physical symptoms (r = -0.36). The study shows that the subjective quality of life of long-term survivors after heart transplantation is similar to that of healthy individuals of the same age group. Thus, survival is certainly not the only indicator of success; aspects of quality of life must also be included in cost effectiveness and/or cost benefit considerations in transplantation policies.


[Electrocardiographic diagnosis of acute graft rejection after heart transplantation]. In order to evaluate the diagnostic value of standard-ECG (ST-ECG) and precordial mapping-ECG with 63 unipolar leads (PM-ECG) for detection of acute cardiac allograft rejection, 15 patients (12 male, 3 female; age range 24-64 years) were studied. ST-ECG and PM-ECG were recorded along with 94 endomyocardial biopsies. Twenty-four acute rejections were detected histologically. Using the ST-ECG, a reduction of the QRS-amplitude-sum (lead I, II, III, V1 and V6) greater than or equal to 5% in comparison with the ECG obtained 1 week before was found to be the best diagnostic criterion (sensitivity 63%, specificity 74%, positive predictive value 48%, negative predictive value 85%). By analysing the PM-ECG a drop of the QRS-amplitude greater than or equal to 12% in greater than or equal to 14/63 precordial leads was determined to be the most reliable parameter (sensitivity 79%, specificity 71%, positive predictive value 49%, negative predictive value 91%). In contrast to the high sensitivity of PM-ECG, ST-ECG was less suitable for detection of acute rejection. However, taking into account the high negative predictive value of PM-ECG, acute rejection could be excluded with high probability, if the QRS-amplitudes of the PM-ECG remained stable. This may lead to a lower frequency of routinely performed endomyocardial biopsies.


[The effect of bovine surfactant in premature infants with respiratory distress syndrome. Results of an open, multicenter study]. We investigated the effects of a bovine surfactant (SF-RI 1, Alveofact) in very low birth weight infants (VLBW, b.w. 500-1500 g) with established respiratory distress syndrome (RDS; definition: FiO2 greater than or equal to 0.6 or peak inspiratory pressure greater than 22-28 cm H2O). Fifty mg/kg b.w. bovine surfactant was administered intratracheally as a bolus, if the acute response was unsatisfactory (FiO2 greater than 0.5), further administrations of surfactant up to a maximum cumulative dose of 200 mg/kg b.w. were permitted. One hundred and sixty-four VLBW infants (gestational age 28.0 +/- 2 wks; b.w. 1054 +/- 251 g; mean +/- SD) with a mean FiO2 of 0.84 +/- 0.15 were enrolled in the study. Maximum improvement in oxygen requirements was observed 1/2 h post administration (FiO2 0.53 +/- 0.22); incidence of complications during the neonatal period: pulmonary interstitial emphysema 26%, pneumothorax 10%, patent ductus arteriosus 37%, intracranial hemorrhage 47%. The overall survival rate was 61%, survival rate without bronchopulmonary dysplasia (BPD) was 47%. A multiple regression analysis was performed in order to identity factors determining survival without BPD (p less than or equal to 0.05). We observed a positive correlation for gestational age and birth weight and a negative correlation for pretreatment oxygen requirements. For further optimizing surfactant-therapy in VLBW infants with RDS, studies are mandatory using intervention criteria at lower FiO2-values and higher initial doses of bovine surfactant.


[Umbilical cord complications as a cause of intrauterine fetal death]. In a group of 71 intrauterine fetal deaths in monozygotic pregnancies, umbilical cord complications were the cause of death in 11 cases (16%). These included 5 umbilical knots, 3 loops, and one case each of torsion with constriction, umbilical prolapse and velamentous insertion (with rupture of the umbilical vessels). The relative importance of these umbilical complications is pointed out and discussed in regard to clinical and pathological factors.


[Magnetic resonance tomography image of transmural myocardial infarct in comparison with 99mTc-methoxyisobutylisonitrile SPECT]. To assess the ability of magnetic resonance imaging (MRI) to identify morphologic and functional abnormalities associated with transmural anterior and inferior myocardial infarction, 18 patients with anterior myocardial infarcts and 11 patients with inferior myocardial infarcts confirmed by ECG and cine-ventriculography underwent gradient-echo MRI of transverse and short-axis imaging planes. Myocardial perfusion of corresponding imaging planes was measured by 99mTc-methoxyisobutyl-isonitrile single-photon emission computed tomography (MIBI-SPECT). Transmural scar by MRI was defined as diastolic wall thickness 2.5 SD below corresponding normal values of a healthy control group (n = 21). MIBI-SPECT scar was defined as a MIBI uptake less than 2.5 SD below mean values of a healthy control group (n = 11). By MIBI-SPECT, 231 segments contained normal tissue and 161 contained scarred myocardium. In 352/392 (90%) segments gradings based on diastolic wall thickness and MIBI-SPECT gradings were identical. Diastolic wall thickness was significantly higher in normal than in scarred MIBI-SPECT segments (10.3 +/- 1.5 vs 5.2 +/- 2 mm, p less than 0.0001). Additionally, normal segments by MIBI-SPECT showed significantly higher systolic wall thickening than scar segments (5.5 +/- 1.5 vs 0.6 +/- 1.6 mm, p less than 0.0001). The correlation between MRI and MIBI-SPECT assessed infarct size was r = 0.91 for anterior and r = 0.77 for inferior myocardial infarcts. The agreement between MIBI-SPECT perfusion defect size and regions with reduced diastolic wall thickness on MRI tomograms was significantly better for anterior myocardial infarcts than for inferior myocardial infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)


[Indium-111 or Tc-99m-HMPAO marked granulocytes as specific markers of florid stage endocarditis--results comparing clinical, histological and scintigraphic findings in 30 patients with suspected endocarditis]. Thirty patients with clinically suspected infective endocarditis were scanned with Indium-111- or Tc-99m-HM-PAO-labeled granulocytes. The scans were correlated with the clinical course, and in 20 cases with the results from histologic examination of the valves. In six cases the scintigraphic examination gave correct positive results, in three cases false negative, in one case a false positive, and in 20 cases correct negative results. If we limit the analysis to only the histologically proven cases, our data suggest a specificity of the method of 86% and a sensitivity of about 67%.


[Effects of prostaglandin E1 analogs on the cervix--observations with vaginal sonography]. In this study participated 17 patients, in whose pregnancies not viable malformations or intrauterine deaths were diagnosed. The termination of the pregnancies was done with PG-E-1 suppositories Gemeprost (Cergem) 1 mg. Collectively the patients received 3 Cergem suppositories applicated all 3 hours. Before beginning therapy and every 4-6 hours a vaginosonography was done. The cervical changes under the influence of Gemeprost were documented vaginosonographically. The measurements before Gemeprost treatment showed an average cervical length of 44.2 +/- 6.3 mm, a width of 29.5 +/- 1.7 mm and an internal os of 2.5 +/- 0.5 mm. The results of the second ultrasound showed a length of 30.6 +/- 4.1 mm, a width of 32.3 +/- 2.5 mm and an internal os of 7.0 +/- 3.0 mm. The last measurements (ca. 107 minutes before abortion) showed a remaining of cervical length of 15.2 +/- 4.5 mm, a width of 41.5 +/- 4.6 mm, an internal os of 19.2 +/- 4.1 mm and the amniotic membranes bulged into the cervical channel.


[Diagnosis and therapy of hemodynamic disorders. A contribution to the management of pregnancies with threatened premature labor]. 114 pregnant women (without multiple pregnancies) with premature labour were examined in a randomized prospective study. Pulsatility index (PI) in the uterine artery and fetal thoracic aorta was the parameter we used for the examination, the determination of which was done with doppler sonography at the time of hospital admission. Therapy with beta-sympathomimetics alone or additionally either Oxygen inhalation therapy or transcutaneous dorsal nerve stimulation were conducted and the pulsatility index was controlled at intervals of one and two weeks after initiation of the aforementioned therapy. The negative correlations which we determined between pulsatility index and prolongation of duration of pregnancy, gestational age at the time of delivery and birth weight were significant. This confirms the clinical importance of maternal perfusion already at the time of admission for the clinical end-results. Similarly significantly negative correlations between pulsatility index of uterine vessels, weight percentile of the corresponding newborns and antenatal CTG scores (Fischer) verify the close connections between the hemodynamic, nutritional and respiratory partial functions of the fetoplacento-maternal unit. The clinical results after normalization of an impaired perfusion were found to be improved significantly after a combined therapy with beta-sympathomimetics and transcutaneous dorsal nerve stimulation (TNS) as compared with beta-sympathomimetic therapy alone. These results justify the recommendation that doppler sonographic measurements of utero-placental perfusion can be used for the diagnostic and therapeutic concept in pregnancies with premature labour.


[Initial clinical trial of a multi-planar transesophageal echoscope]. The prototype of a multiplanar transesophageal echocardiographic transducer was evaluated clinically. This 5 MHz, phased array, 64-element transducer allows to continuously rotate the imaging plane from the transverse (0 degree) position to a maximal 180 degrees position, thus encompassing transverse, longitudinal, and every intermediate position. The transducer is incorporated in the echoscope tip measuring 16 by 11 by 40 mm. The shaft of the instrument is 110-cm long and has a 9-mm diameter. The instrument has pulsed wave, continuous wave, and color Doppler capabilities. 176 clinical patients were examined with the multiplane transducer. No complications occurred. Advantages of this transducer included: 1) comprehensive scanning of the whole mitral circumference and mitral valve; 2) quick and precise alignment of aortic valve long and short axis views, including long axis views of the ascending aorta, with a mean visualized length of 6 cm; 3) improved imaging and evaluation of transvalvular and paravalvular regurgitant jets in mitral and aortic valve prostheses; 4) complete evaluation of all left ventricular segments using multiple planes from transgastric and transesophageal transducer positions. An important potential application is three-dimensional reconstruction of cardiac structures and color Doppler jets.


[Cervix reconstruction after amniotic fluid puncture in amniotic sac prolapse in the second trimester]. The possibility and the problems of an surgical technique because of cervical insufficiency in the 2. trimester with a hourglass amniotic prolapse is shown in three cases. A new concept including amniocentesis and doubleclerclage is developed with a wide physiological reconstruction of the cervix and its occlusion mechanism at the inner and outer cervix. We show an alternative to previous surgical techniques that makes a prolongation of the pregnancy possible and causes additionally because of the minimal surgical procedure no disadvantage for the cervical function in coming pregnancies. Small surgical strain, quick surgical procedure and simultaneously continue of diagnostic possibilities as well as the reconstructive technique with small trauma of the cervical tissue are the advantages of this method.


[Morphology of aortic isthmus stenosis--invasive study using intravascular ultrasound]. In patients with coarctation of the aorta, intravascular ultrasound can yield important additional diagnostic information concerning stenosis morphology and aortic wall structure that, thus far cannot be obtained with conventional angiography. For the first time, we were able to visualize, in vivo, the eccentric thickening of the posterior aortic wall, which is the typical morphological finding in patients with coarctation of the aorta, known from post mortem or intraoperative specimens. The additional information about stenosis morphology and aortic wall structure, obtained with intravascular ultrasound, is especially valuable for the newer interventional therapy of balloon angioplasty. With intravascular ultrasound, not only the direct quantitative assessment of the aortic cross-sectional luminal area, but also the immediate visualization of local dissections and aneurysms is possible. Using special angioplasty catheters with integrated ultrasonic crystals (which are currently under manufacturing development), a step-wise dilation with immediate evaluation of the therapeutical success may improve the short- and long-term results of balloon angioplasty. At present, intravascular ultrasound is still only an additional diagnostic tool. If it is combined with interventional balloon angioplasty, however, it could gain increasing clinical importance for the treatment of aortic coarctation in the near future.


[Control of catheters in coronary angiography--resistance to torsion in the aortic arch]. A curved catheter, unlike a straight catheter, cannot be rotated around its longitudinal axis without resistance. In a curved catheter section, the torsion causes internal deformation of the material which consumes energy and which is associated with resistance to rotation. This resistance can be measured in terms of a moment of torsion (Nm); it greatly differs in magnitude depending on the cross-section of the catheter and on the catheter material. This resistance to rotation must always be reckoned with in transfemoral coronary angiography, as a consequence of the semicircular curvature of the catheter. The controllability of the catheter therefore does not depend solely on its (likewise measurable) torsional stability, but rather on the ratio between the torsional stability and resistance to rotation in the aortic arch. In the 20 catheter types of caliber 7F, 6F, and 5.2F investigated, the corresponding measurement results were the most favorable for 6F braided nylon catheters.


[Unpreventable effects of neonatal intensive care on the later development of extremely small premature infants]. This review of the literature presents the pooled data from several perinatal centers throughout the world published during the last three years. It regards the longterm prognosis of extremely low birthweight infants (less than 1000 g). Since the introduction of neonatal intensive care the mortality rate dropped from greater than 90% to less than 50%. On the other hand the morbidity rate improved only slowly. Recent reports from the Anglo-American literature show that among the survivors 13.7% are seriously and 25.1% mildly handicapped. 60-70% of the extremely low birthweight infants, despite of normal IQ's, are experiencing school problems. Most of them have cognitive, perceptual and motor deficits combined with behaviour problems ("the new morbidities"). The incidence of cerebral palsy remained unchanged (6-8%) over the last two decades. Until now, there is no significant effect of the surfactant therapy on the morbidity rate. The rate of serious longterm disability increases with decreasing birthweight. The results of the Anglo-American and German follow-up studies differ only slightly.


[Complications during directional coronary atherectomy (DCA): catheter fracture between housing assembly and shaft point with subsequent vascular occlusion]. Directional coronary atherectomy of a severe stenosis of the left anterior descending coronary artery was complicated by device fracture between the cylindric housing portion and the distal nose-cone collecting chamber. After successful removal of the DCA device, an early occlusion of the coronary vessel occurred, which could be successfully treated by perfusion balloon catheter.


[Dysplastic intramyocardial arteries with subaortic septum in patients with hypertrophic obstructive cardiomyopathy]. Abnormal, dysplastic intramyocardial arteries were reported in autopsied hearts of hypertrophic cardiomyopathy. To elucidate their significance, the operatively-excised myectomy specimens of 24 patients with hypertrophic-obstructive cardiomyopathy (HOCM), of 18 patients with valvular aortic stenosis and of 10 postmortem normal hearts were investigated. Eight patients with HOCM had dysplastic intramyocardial arteries (greater than 100 microns external diameter) as well as dysplastic arterioles (less than 100 microns external diameter). The value of the scores for the thickness and fibroelastosis of the media was nearly doubled, the tunica intima was frequently thickened, and the lumen was relatively reduced in dysplastic vessels. Neither in controls nor in aortic stenosis dysplastic arteries were found. Volume density of patchy fibrosis (scars) was increased in patients with dysplastic arterial vessels (HOCM II) (7.2 +/- 4.4 Vv%) (p less than or equal to 0.05) as compared with HOCM without dysplastic vessels (HOCM I) (0.8 +/- 2.3 Vv%), with aortic stenosis (0.9 +/- 1.6 Vv%) or with controls (0 Vv%), Patients with HOCM II were significantly (p less than or equal to 0.05) younger (30 +/- 13 years) than those with HOCM I (53 +/- 12 years), aortic stenosis (56 +/- 12 years), or controls (63 +/- 21 years). The anterior septum was significantly thicker in HOCM II (29 +/- 7 mm) than in HOCM I (22 +/- 4 mm), in aortic stenosis (19 +/- 3 mm), or in controls (12 +/- 2 mm). Syncopes were complained by about 75% (6/8) of patients in HOCM II, by 54% (9/16) in HOCM I, and by 44% (8/18) in aortic stenosis (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)


[Legal aspects of geriatric rehabilitation]. Nowadays geriatric rehabilitation is recognized as a matter of social law performance. Nevertheless there are very small chances to realize corresponding legal claims in view of the infra-structural deficits. This subscription works out the claims of social law for geriatric rehabilitation, names questions of delineation between illness, prevention and care indigence and discusses problems of geriatric rehabilitant institutions and services.


[20 years geriatric rehabilitation at the Hannover at the Henrietta Foundation]. This report includes the historical formation of the institution in regard to the background of the development of the German Society of Gerontology. A description of the newly formed clinic and its special institute for geriatric rehabilitation is supposed to provide a survey about the conditions of clinical work as well as the special courses and training possibilities. This is followed by the presentation of treatment methods and results.


[The dynamics of aging and rehabilitation following coronary bypass operation]. The dynamics of aging encompass the topics "aging of society" and "coping with chronic illness". Both are discussed using data from a qualitative study on return to work after coronary artery bypass surgery. Data from the retrospective substudy reveal four forms of aging as biographical development toward early retirement, old-age retirement, or related stages. It emerges that the manner of aging is less influenced by medical rehabilitation or medical history, and more by the patient's occupation and socio-economic status. Case reports are used to show that social class is a facilitation context, but not a determining force, regarding the choice between postoperative retirement or return to work. The final section briefly discusses whether the findings concerning the dynamics of aging of the cohort operated on in the late 1970s apply also to that of the cohort operated on in the late 1980s; this is addressed using some data from the prospective sub-study.


[The rehabilitation potential of the elderly]. This contribution points to the existence of potentials for rehabilitation in the elderly and underlines the necessity of rehabilitation in chronically ill patients. Especially important for the success of rehabilitation is a differential diagnosis and treatment. The potentials for rehabilitation differ among the several functions, abilities, and skills. For this reason, a differential profile of the rehabilitation potentials is necessary. Theoretical and empirical contributions to the plasticity, to developmental potentials, and to competence in the elderly form the basis for prognosis of rehabilitation potentials in old age. It is made clear that realizing these potentials is not only a task of the patient, but is also dependent on the ecological and social environment.


[The role of nursing care in geriatric rehabilitation]. This article intends to present goals, tasks and focus points in different kinds of institutions of geriatric rehabilitation. This is be done under the aspects of: 1. Accompanying handicappeds during their disease. 2. Nursing orientated of activities in daily life. 3. Nursing with a multiprofessional team and its role within the rehabilitative concept. Besides this, goals and development strategies in professional nursing will be worked out.


[Current classification of primary malignant bone tumors]. The classification of primary malignant bone tumors has to include: 1. Histologic diagnosis, iusing immunohistochemistry especially in small-round- and spindle-cell tumors. 2. Grading of malignancy, iusing proliferation factors. 3. Definition of compartmentalisation. 4. Staging. Only when all these factors are defined it is possible to plan the best therapy, to compare the results of different centers and to overwork it scientifically. Investigation of chromosomes, oncogenes, chemotherapy resistance a.o. are to be added for classification in next future.


Falls and lying helpless in the elderly. Twelve percent of men and 19% of women aged 65 years and over who sought medical attention after a fall, lie where they fell for 15 min or more after falling. The occurrence of a fall with a long period of lying helpless was associated in bivariate analyses with severe injury, an intrinsic or unknown mechanism of falling, falling indoors, poor functional capacity, use of walking aids, body temperature 37.5 degrees C or over, and serum potassium concentration under 3.5 mmol/l. A log-linear model showed that a fall with a lie of this kind was related independently to high body temperature, low serum potassium concentration, and severe injury. The occurrence of such a fall due to an extrinsic mechanism was related to poor functional capacity, but no similar relationship could be found when the fall was due to an intrinsic or unknown mechanism.


[Neuropsychological therapy at the computer with the elderly]. Since the end of the 1970s, computers have been used in neuropsychological rehabilitation. This article points out the possibilities, as well as the limits in using computers with the elderly, and is focused on their particular needs. Furthermore, indications are listed whereby computers in neuropsychological therapy in Albertinen-Haus, Hamburg, FRG, have been applied. The need for a neuropsychological diagnostic is shown and illustrated with test examples. Finally, four individual case studies are discussed.


[Osteosarcoma].

[Osteosarcoma]. Osteosarcoma includes several distinct varieties. It is therefore essential to rely upon a very specialized pathologist. It is necessary to stage the tumor and to histologically define the oncologic quality of the surgical removal (surgical margins). The limb salvage surgery in osteosarcoma involves several areas of risk: the biopsy, the extension of the tumor in the marrow spaces and canal, the impingement or plugging of the vessels by the tumor, the invasion of the joint tissues, the contamination of the joint space and/or soft tissue compartments. The reconstruction after bone segmental resection involves many problems, including long-lasting prostheses, bone bank, microsurgical techniques--the preoperative chemotherapy dramatically reduced the need for amputation, in favour of conservative surgery. A good response to chemotherapy (almost total necrosis of the tumor), is the most important factor correlated with a favorable prognosis. The more recent protocols aim to increase the tumor response and the survival rate through a very intense primary chemotherapy, using Adriamycin, high-dose Methotrexate, Cisplatin and Ifosfamide.


[Legal evaluation of bone tumors].

[Legal evaluation of bone tumors]. Three topics are of major importance in the legal evaluation of bone tumors: The questions of medical liability, of causality and of medical evaluation. Concerning medical liability, the legal consequences of proven cases of malpractice are stressed. A causal connection between an accused trauma and the occurrence of a malignant bone tumor can be denied in nearly all circumstances. Due to the well known occurrence of a secondary sarcoma, the irradiation of a benign bone tumor or tumorlike lesion is strongly disfavored. In cases of medical evaluation, patients with malignant bone tumors should be judged by the same criteria as patients with any other diseases and impairments.