[Combination of DRD4 and DAT1 genotypes is an important risk factor for attention deficit disorder with hyperactivity families living in Santiago, Chile]. / Combinación de genotipos DRD4 y DAT1 constituye importante factor de riesgo en miembros de familias de Santiago de Chile con déficit atencional.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. AIM: To search for possible associations between dopamine receptor D4 (DRD4) and dopamine transponder 1 (DATl) polymorphisms and ADHD in Chilean families. MATERIAL AND METHODS: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV criteria and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. RESULTS: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5%) in cases (40), compared with (2.8%) unaffected siblings (36), with an odds-ratio of 10.16. CONCLUSIONS: The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of studies to understand the functional basis of ADHD.

Combinación de genotipos DRD4 y DAT1 constituye importante factor de riesgo en miembros de familias de Santiago de Chile con déficit atencional / Combination of DRD4 and DAT1 genotypes is an important risk factor for attention déficit disorder with hyperactivity families living in Santiago, Chile

Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Aún: To search forpossible associations between dopamine receptor D4 (DRD4) and dopamine transponer 1 (DATl) polymorphisms and ADHD in Chilean families. Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV entena and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. Results: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5 percent) in cases (40), compared with (2.8 percent) unaffected siblings (36), with an odds-ratio of 10.16. Conclusions: The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of studies to understand the functional basis ofADHD.

[Frequency distribution of dibucaine numbers in 24,830 patients]. / Verteilungsmuster der Dibucainzahl bei 24.830 Patientinnen und Patienten.

PURPOSE: Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. METHODS: Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. RESULTS: A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. CONCLUSIONS: An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.

[Rocuronium or vecuronium for intubation for short operations in the preschool age? Effects on time in the operating room and postoperative phase]. / Rocuronium oder vecuronium zur Intubation bei kurzen Eingriffen im Vorschulalter? Auswirkungen auf den Zeitablauf im Operationssaal und die postoperative Phase.

This prospective randomized study compares the effects of rocuronium (R) and vecuronium (V) on the early postoperative period in infants. Forty-eight infants between the ages of three and six, scheduled for elective ENT procedures, were studied after prior approval of local ethics committee and informed parental consent. All children were premedicated with chlorprotixene and belladonna. Anaesthesia was induced with 5 mg/kg thiopentone and 1 vol.-% halothane. Subsequently, 0.4 mg/kg rocuronium or 0.075 mg/kg vecuronium were administered, respectively. Anaesthesia and post-operative care were conducted by independent anaesthetists, who were unaware of the drug used and of the relaxometric data obtained. All children were monitored in the recovery room by pulse oximetry until they reached a Steward Score of 6. Demographic data did not differ between the groups. No differences were recorded between the non-depolarizing relaxants regarding intubation time (R: 24.1 +/- 4.2 min, V: 25.8 +/- 6.8 min) and the time interval from end extubation to leaving the operating theatre (R: 2.3 +/- 0.8 min, V: 2.6 +/- 1.2 min), respectively. Similarly, no differences in SaO2 were noted during the recovery period in the recovery room. Significant differences between the non-depolarizing relaxants were found in the TOF-ratios at extubation (R: 0.73 +/- 0.31 min, V: 0.48 +/- 0.34 min) and arrival in the recovery room (R: 0.88 +/- 0.21 min, V: 0.69 +/- 0.26 min). 0.4 mg/kg Rocuronium and 0.075 mg/kg vecuronium can be used for intubation during short operations on pre-school children. Rocuronium may be the better alternative, due to its faster neuromuscular recovery properties.

Genética de los desórdenes adictivos / Genetics of addictive disorders

Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an heredability of roughly 38 percent, whereas psychostimulant and opiate use exhibit heredabilities of 11 to 45 percent. The heredability of smoking was found to be around 50 percent. There is a strong comorbidity between alcoholism and smoking. More than 80 percent of alcoholics smoke cigarettes in the U.S.A.. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-IB serotonin receptor and the DRDI, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster

[Tissue oxygenation: physiological and pathophysiologic aspects in intensive care]. / Gewebsoxygenierung: Physiologische und pathophysiologische Aspekte in der Intensivmedizin.

Continuous oxygen supply to the tissues is one of the many important factors in intensive care. However, as a basic requirement for the structure and function of higher developed organisms energy production by oxydative metabolism is of outstanding importance, because there is no significant storage of energy and anaerobic metabolism is insufficient. The determinants of oxygen supply--blood flow and oxygen content--are well known. The system stands out for its extensive ability to compensate imbalances. Nevertheless one has to bear in mind also rather trivial disturbances like insufficient respiration and hypovolemia. Absolute values of global parameters, however, provide no information on the oxygen supply of individual organs that are variably susceptible to hypoxia. Regional perfusion and tissue respiration are influenced by various factors. Together with systemic components the physiologic oxygen transport along the oxygen cascade follows demand. Regardless of their position on the oxygen cascade malfunctions of oxygenation impair first the function and eventually the structure of the tissues. An utilisation block on the cellular level can prevent sufficient energy production despite optimized oxygen supply, the damage of reperfusion can intensify the effects of hypoxia. Typical haemodynamic patterns follow the tissue hypoxia. For maintaining an equilibrium between oxygen demand and supply it is important that oxygen consumption is also influenced by numerous factors. Only when an imbalance between oxygen supply and demand--an oxygen debt--is realized at an early stage, the critically ill patient can be saved from irreversible damage. In the field of intensive care the frequently latent tissue hypoxia is often a result of the chronic oxygen debt of individual, particularly vulnerable organs. Considering those aspects the intestinal mucosa is particularly suited for the monitoring of tissue oxygenation in the critically ill patient.

[Gastric mucosa tonometry in routine monitoring in the surgical intensive care unit]. / Magenmukosa-Tonometrie im Routinemonitoring auf der operativen Intensivstation.

PURPOSE: Monitoring tissue oxygenation in the splanchnic region could be helpful for critically ill patients. In this study the postoperative course of gastric mucosal CO2 (prCO2) in 40 patients is shown. METHODS: Following approval of the ethics committee, 24 patients schedulded for surgery with an expected large fluid turnover and 16 multiple injured patients were monitored with a gas tonometry device in addition to standard monitoring (ECG, pulse oximetry, capnometry, CVP, arterial pressure). Normoventilated patients with prCO2 > 50 for more than 30 minutes were treated with fluid therapy, followed by catecholamine therapy, followed by transfusion (fig. 1). All patients were admitted to the SICU post-operatively. RESULTS AND DISCUSSION: The variation of prCO2-values was greater in multiple injured patients. Their prCO2-values began in a lower range compared to patients with scheduled operation, became higher at the end of the first SICU-day and remained higher thereafter. They had a higher fluid turnover and needed more catecholamines. Multiple injured patients with an arterio-intestinal CO2-Difference (CO2-Gap) > 10 had a higher ISS-Score, were longer mechanically ventilated, had a longer SICU-stay and a higher incidence of complications in comparison to patients with aCO2-Gap < 10. Perhaps a CO2-Gap > 10 could be predictive for a more severe course in intensive care patients.

[Nitrous oxide in combination anesthesia. Quantitative aspects of the effect of nitrous oxide]. / Lachgas in der Kombinationsnarkose. Quantitative Aspekte des Wirkanteils von N2O.

UNLABELLED: Minimal Alveolar Concentration (MAC) defines the anesthetic potency of nitrous oxide (N2O) combined with an inhalational anesthetic only for the moment of skin incision. For the complete operation, the proportional action of N2O is unknown. This prospective, randomized study reports the mean intraoperative concentration (MIC) of halothane with and without 70% N2O in combination with premedication, i.v. induction, and muscle relaxation for the duration of operation. METHODS: Forty ASA I-II patients scheduled for hysterectomies gave informed consent. All patients received atropine 0.5 mg, promethazine and pethidine 1 mg/kg i.m. 30-45 min prior to anesthesia, i.v. induction with thiopental, and neuromuscular blockade with alcuronium at the beginning of the operation. Post-induction, patients received randomized halothane in 30% O2/70% N2 (group 1, n = 20) or in 30% O2/70% N2O (group 2, n = 20). In the course of this observation (before induction and up to 15 min after extubation), the following parameters were measured (Table 1): arterial pressure (AP), heart rate (HR), plasma concentrations of growth hormone, prolactin, and cortisol in central venous blood, esophageal temperature, "train-of-four" ratio, and expiratory CO2 concentration. MIC had been computed from the integral of end-expiratory halothane concentration during the course of the operation. RESULTS: Biometric data and concomitant conditions were equivalent within the two groups (Table 2). MIC halothane was 0.72 +/- 0.014 vol% in group 1 (O2/N2) and 0.52 +/- 0.01 vol% in group 2 (O2/N2O).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic side effects of high-frequency jet ventilation as a function of lung volume. Impedance spirometric studies]. / Hämodynamische Nebenwirkungen der High-Frequency Jet Ventilation (HFJV) als Funktion des Lungenvolumens. Impedanzspirometrische Untersuchungen.

In five patients with acute respiratory insufficiency the changes in tracheal pressure (P), lung volume (V) and transthoracic electric impedance TEI (Z) were measured during delayed expiration all over the inspiratory capacity (IC) from TLC to FRC. The quasi-static V/Z- and Z/P-curves were two-dimensionally displayed, and the Z/P-curve was volume-calibrated on the Y-axis (Z) using the linear V/Z-relationship. During high-frequency jet ventilation (HFJV, 200/min), the Z- and P-excursions were displayed on the "frozen" Z/P-curve as flat discs. By well-aimed increase in driving pressure and I/E-ratio the unknown FRC was enhanced in 4 stages (I-IV) by 0.33 IC, 0.5 IC, 0.66 IC and 0.75 IC, to measure haemodynamic reactions 10 minutes later (Swan-Ganz catheter). The pulmonary vascular resistance remained unchanged between stage I and II. It changed moderately in stage III (+14%) and was found to be markedly increased in stage IV (+45%). The increase in PVR was well parabolically correlated (r = 0.88) to the fraction of IC by which FRC was expanded. In a previous study a very similar function could be documented by us for the end-inspiratory lung volume during conventional PEEP ventilation. Concomitant to the increase in PVR the CI fell linearilly (r = 0.95). We conclude from our results: 1. TEI may be of value in monitoring HFJV. It offers the possibility to measure the increase in lung volume ("PEEP effect") and to titrate it deliberately within the usable volume range IC. 2.(ABSTRACT TRUNCATED AT 250 WORDS)

[Life-threatening anaphylactoid reaction following etomidate]. / Lebensbedrohliche anaphylaktoide Reaktion nach Etomidat.

In a patient scheduled for coronary artery bypass grafting induction of anaesthesia resulted in a life-threatening anaphylactoid reaction with development of an erythema of the neck. Severity and duration of hypotension and tachycardia were such as to require intensive management and postponement of surgery. Skin tests ruled out any other cause except etomidate. Hence for definite surgery exactly the same induction manoeuvre was chosen, but etomidate was omitted. Anaesthesia and surgery proceeded completely uneventfully. There can be no doubt that this anaphylactoid reaction (grade III according to the classification proposed by Lorenz and Doenicke) was caused by etomidate.

[Myoelectric activity of the colostomy with sphincter muscle replacement]. / Myoelektrische Aktivität an der Colostomie mit Schliessmuskelersatz.

A continent colostomy was performed on 15 mongrel dogs by free transplantation of autologous smooth muscle. The myoelectrical observations of this colostomy and of a 3 years old human transplant show a vital and high active sphincter mechanism.

[Control of the position of central venous catheters by intracardial ECG. A presentation of the method and its advantages compared to roentgen control]. / Lagekontrolle zentralvenöser Katheter mit dem intrakardialen EKG. Eine Darstellung der Methode und ihrer Vorzüge gegenüber der Röntgen-Kontrolle.

It is obligatory to control the localization of a central venous catheter. We describe a simple own method for controlling the correct position of a central venous catheter electrocardiographically. The reported method is accurate and inexpensive.

[Spontaneous motility of the human taenia coli under morphine, thiopental and dehydrobenzperidol]. / Die spontane Motilität menschlicher Dickdarmtaenie unter Morphin, Thiopental und Dehydrobenzperidol.

Intestinal dysfunction is well known after narcotic analgesics and anaesthetics. The site and extent of this action is not really known in man. We investigated the direct effect of morphine, thiopentone and droperidol on human taenia libera in vitro. The spontaneous motility of strips of fresh resected human taenia libera induced by a suitable preload was observed by isometric measurement of developed tension. Cumulative doses of morphine 1 X 10(-8) - 3.89 X 10(-6) g/ml, thiopentone 2.5 X 10(-6) - 9.75 X 10(-5) g/ml or droperidol 2.5 X 10(-8) - 9.72 X 10(-6) g/ml were added to the bath solution. The following parameters were analysed: amplitude, frequency and performance (Montevideo Units MU) of the spontaneous contractions and also the basal tone between contractions. Morphine showed no effects. Thiopentone reduced basal tone to 45.5% of the initial value and frequency to zero. The amplitude of contractions and the MU decreased with thiopentone more than 22.5 X 10(-6) g/ml. All effects are reversible. Droperidol has no significant effects with the exception of a light increase of frequency in high doses. The well known in vivo effect of morphine is therefore not induced by direct action on the smooth muscle of human intestine. Thiopentone in high dose can reduced intestinal motility by direct action on the smooth muscle. Droperidol in the dose used is probably without clinical relevance.