Peripheral versus central cannulation for extracorporeal membrane oxygenation: a comparison of limb ischemia and transfusion requirements.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be instituted centrally, through the right atrium and ascending aorta, or peripherally, most commonly using the femoral artery and vein. We sought to investigate the impact of the mode of cannulation on the incidence of limb ischemia, perfusion and overall morbidity. METHODS: A retrospective analysis of 50 consecutive patients over 5 years who underwent ECMO by central or peripheral cannulation was performed. RESULTS: There was no difference in the incidence of limb ischemia and end-organ perfusion when peripheral and central cannulation cohorts were compared. Central cannulation was associated with a higher incidence of bleeding from the cannulation site (64% vs. 18%, P = 0.002), blood product utilization and reoperation (66% vs. 14%, P < 0.0001). 30-day mortality was similar in both cohorts (46% peripheral, 50% central, P = 0.8). CONCLUSION: Our results suggest that there is comparable tissue perfusion and limb ischemia with both cannulation techniques. Central cannulation is associated with a higher incidence of bleeding, higher transfusion rates, a greater need for reoperation and greater resource utilization. Therefore, peripheral cannulation is safe and may be advantageous in certain clinical scenarios.

Left ventricular epicardial lead implantation via left minithoracotomy.

OBJECTIVE: The transvenous placement of left ventricular epicardial leads is limited by long procedure times, high procedural failure rates and limited sites for lead placement. Open surgical approaches are used primarily after failure of the transvenous approach but provide additional important benefits. This study assesses the surgical outcomes of left anterior minithoracotomy for the implantation of left ventricular epicardial pacing leads in cardiac resynchronization therapy. METHODS: Eleven patients were referred for open left ventricular epicardial lead placement. Mean patient age was 66.2 (59-77) years. The patients had New York Heart Association class III (II-IV) heart failure, a mean left ventricular ejection fraction of 18 +/- 5 % and mean QRS duration of 177 +/- 29 milliseconds. RESULTS: Left ventricular epicardial leads were successfully placed in all patients. Mean surgery time was 101 +/- 33 minutes and intraoperative lead parameters were: R wave 14.5 +/- 9.8 millivolts, lead threshold 1.4 +/- 0.9 volts at 0.5 milliseconds, impedance 1127 +/- 693 ohms. Impedance was statistically different at 40 +/- 25 weeks with 571 +/- 199 ohms ( P = 0.033). CONCLUSIONS: Left ventricular epicardial lead implantation via left anterior minithoracotomy is safe and effective.

Distress call reactivation in isolated chicks: a behavioral indicator with high selectivity for antidepressants.

Four-day-old chicks respond to isolation with distress calling. A decrease in distress calling during isolation seems to reflect some general aspect of depressive syndrome and appears to be sensitive to pharmacological manipulation. Diverse clinically active antidepressants are able to counteract this decrease with high selectivity; non-antidepressants have either no influence or further inhibit the distress calling.

Pharmacological and neurochemical properties of 1,4-diazepines with two annelated heterocycles ('hetrazepines').

1,4-Diazepines with two annelated heterocycles ('hetrazepines') such as brotizolam (WE 941), WE 973 and WE 1008 bind with high affinities to benzodiazepine receptors in the central nervous system. Brotizolam has a pharmacologic spectrum of action similar to clinically useful benzodiazepines, while the closely related derivatives WE 973 and WE 1008 appear to lack hypnotic action. Unlike other benzodiazepine receptor ligands which share common pharmacologic properties with the benzodiazepines, the apparent affinities of WE 973 and WE 1008 are not increased significantly in the presence of GABA, even at an elevated incubation temperature. Furthermore, the apparent affinities of these compounds do not appear to be reduced as a result of increasing the incubation temperature. Brotizolam, like the benzodiazepines, facilitates GABAergic transmission in zona recitulata neurons of the substantia nigra. In contrast, at a dose which inhibits cell firing, WE 973 does not appear to significantly augment the inhibitory action of GABA in these cells. These observations suggest that the so-called 'GABA shift' may not be a valid means of distinguishing benzodiazepine-like compounds in vitro. Furthermore, these data suggest that facilitation of GABAergic transmission may be necessary for the hypnotic action of benzodiazepine receptor ligands, but not for the anticonflict or the anticonvulsant actions of such compounds.

Relationship between birth order and leadership style for nursery school children.

36 nursery school children were given a revised form of Fiedler's (1967) least preferred co-worker scale designated as the least preferred playmate scale. The purpose was to investigate the relationship between least preferred playmate scores and the birth order of young children. A 2 X 2 contingency table was constructed between birth order (first and later born) and leadership style (high and low). The resulting chi squares were insignificant for the total population and for males. However, for females the results were significant with a higher percentage of firstborns being task-oriented (low score) and a higher percentage of later borns being relation-oriented (high score).

[Aging in Mexico]. / Altern in Mexiko.

Demographic social and economic aspects of the situation of the elderly in Mexico are described with special emphasis upon education programmes and types of care in nursing homes. Considering the future trends of an increase in Mexico's elderly population, the author calls for more efforts in research and training in the field of gerontology. First results in this area are reported.

Long-term services in Mexico: homes for the aged.

Accurate statistics are not available about the number of people in institutions for the aged in Mexico, but the majority are assumed to live with their family or on their own and to be integrated with the community. However, the increase of Mexico's aging population, from its present more than 4 million to 12 million people over 60 years of age in the year 2025, together with the decreased population growth rate (3.5% in the early seventies; approximately 2.5% currently, and 1% in the year 2000) will considerably increase the demand for health care and services for this sector of the population. Nursing Homes should be not only shelters, but should help to raise or maintain the quality for life of elderly people in all areas: physical, psychological, and social. In the near future, it will be necessary not only to build more homes for the aged, but to develop and implement other forms of care that will allow the elderly to remain integrated with the community. Through home care and substitute homes, families that take care of their elderly relatives can be helped; and direct assistance can be give to old people who wish to be independent.

Therapeutic safety studies of brotizolam in animals.

Comparing dose levels for pentetrazol antagonism or antiaggressive activity with those causing motorial side effects in mice brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-alpha]-1,4-diazepine, We 941, Lendormin) showed consistently larger dose ranges than diazepam. This gives evidence that brotizolam may offer the advantage of not causing motorial side effects during therapeutic use as do many other diazepines.

Effects of drugs on schedule-controlled running of mice in a circular runway.

Partially food deprived mice ran in a 1-m circular runway. Every 30 circuits, diluted evaporated milk was delivered. Under control conditions mice averaged 0.18 circuits/s for 1 h. The rate was reduced to 0.11 circuits/s 1 h after gavage of Tylose (cellulose derivative) vehicle. Amphetamine, chlordiazepoxide and pentobarbital increased the rate of responding over some dose range, but chlorpromazine, clozapine, imipramine and morphine caused only decreases in responding at effective dose levels. The results are generally similar to reports of effects of the drugs on responses of much briefer duration occurring at similar rates.

Pharmacology and hypnogenic properties of brotizolam in animals.

Brotizolam differs in pharmacological profile from other diazepines by virtue of its hypnogenic potency. It increases, whereas other diazepines reduce, sleep in the cat. With increasing doses, the latency to rapid eye movement sleep is lengthened and the proportion is reduced. Brotizolam has anxiolytic, anticonvulsant and muscle relaxant properties. The effective anxiolytic and muscle relaxant doses are somewhat lower than those of diazepam, and the effective anti-convulsant dose is ten times lower. Barbiturate synergism in mice is lower with brotizolam than with diazepam, while alcohol-induced coma is prolonged over the same dose range. Side-effects of brotizolam are similar to those of other diazepines, but the therapeutic range is more favourable. Physical dependence as tested in the monkey seems to be low.

Antiemotional and anticonvulsant activity of brotizolam and its effects on motor performance in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo diazepine with predominantly sleep-inducing properties. Additionally, brotizolam, attenuated conflict behavior in rats and inhibited aggressive behavior in mice and cats. Brotizolam prevented audiogenic seizures in mice, seizures provoked by electroshock in rats and inhibited convulsions elicited by electrical stimulation in the limbic system of cats. Furthermore, brotizolam antagonized seizures induced by the convulsant drugs pentetrazol, bicuculline and strychnine in mice. Motocoordination was not impaired within the effective dose range. Muscle relaxant effects appeared at higher doses only. The onset of effect of brotizolam occurred in the different experiments within 15-30 min, thus indicating a fast enteral absorption and penetration of the blood-brain barrier. The duration of action within the therapeutic dose range was between 2-6 h. The effect of brotizolam was compared with other diazepine derivatives. Brotizolam was more active than diazepam, nitrazepam, estazolam, flurazepam and clonazepam and nearly as active as triazolam.

Pharmacological action of some known and possible metabolites of brotizolam.

The two major metabolites of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) in man are the hydroxylation products We 964 (hydroxylation in the methyl group at 9-position) and We 1061 (hydroxylation in 6-position). A structural isomer originating from the latter, We 1064, was found in the urine of dogs. In the same species the demethylation product We 956 was identified. In line with this demethylation the oxidation product Web 1175 might also be formed but was not yet detected. The dihydroxylated product Web 1073 which could arise either from We 964 or from We 1061 was discovered in monkeys. All compounds were investigated with respect to their pharmacological and acute toxicological properties in various experimental situations in mice and rats, and exhibited a profile of action quite similar to brotizolam. Effects of other kinds did not occur. None of the examined metabolites had a longer duration of action than the parent substance. The strength of activity in the various tests was, with very minor exceptions, less than that of brotizolam. All findings favor the conclusion that the various actions of brotizolam are mainly caused by the latter itself and not by its active metabolites. Also, the duration of action of brotizolam is not substantially determined by the pharmacokinetics of its metabolites.

Test guideline. Behavioral toxicity testing in animal experiments according to section 9, para. 1, No. 2 of the Chemicals Act (Chemikaliengesetz) of the Federal Republic of Germany.

The German Chemicals Act requires that chemicals are tested for behavioral toxicity at stage 2 of the testing procedure, i.e. if more than 1000 annual tons are produced. For this purpose a guideline was developed according to which data on behavioral toxicity are to be collected, which are based on cageside observations during longterm exposure. The protocol covers outer appearance, as well as motor, sensory, autonomic and central nervous system functions. Data are to be reported in tabular form and should be evaluated by taking all aspects of the toxicological profile into account.

Pharmacology of WEB 1881-FU, a central cholinergic agent, which enhances cognition and cerebral metabolism.

The pharmacological effects of the novel compound WEB 1881 FU (4-amino-methyl-1-benzyl-pyrrolidine-2-one-fumarate) were investigated. The tests performed indicate that the compound has cytoprotective as well as metabolism and cognition enhancing and central cholinomimetic properties. The nootropic effects in all tests were more pronounced than those of piracetam, while the central cholinomimetic effects were generally weaker than those of directly acting cholinomimetic agents. However, the typical peripheral cholinergic side effects were not observed. From the results we believe that the stimulating effect of WEB 1881 FU upon the central cholinergic system is modulatory rather than direct. The combination of nootropic and cholinomimetic properties appears favorable for treatment of brain dysfunction in the elderly. Side effects are less serious than with other known cholinomimetics.

General pharmacology of brotizolam in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo-diazepine with profound sedative and hypnogenic properties. The side effects of the drug on general behavior, motocoordination, feeding pattern, body temperature, uropoietic and gastrointestinal functions, cardiovascular system, and respiration, as well as interactions with some biogenic amines are reported and discussed. The findings correlate with those known for other diazepines. Accordingly, effects on motocoordination were prominent, but were limited to an ataxia, whereas even extremely high doses scarcely eliminated the postural reflexes. Sleeping animals could invariably be woken and were capable of locomotion; thus, no comatose condition developed. The cardiovascular functions were not appreciably altered by brotizolam in anesthetized cats, while in conscious dogs minor fluctuations of blood pressure and heart rate occurred. Respiration was clearly inhibited when brotizolam was given intravenously. The cardiovascular effects of acetylcholine, norepinephrine, epinephrine, isoprenaline, and histamine were only slightly modulated. The orexigenic and hypothermic effects equalled those of other diazepines. The functions of kidney, stomach, and intestines were not affected. The entirety of the observations procured in ten different species suggest that brotizolam is well tolerated when given orally.

Family with three apparently balanced t(3;15) (p27;q22) translocation carriers. Association with deficits in language acquisition and mental retardation: a possible example of position effect in man.

A father, son, and daughter had a (3;15) (p27;q22) simple reciprocal translocation. No abnormality in the G-banding pattern was noted. The girl was most severely affected; she had an abnormal phenotype, noticeable delay in receptive and expressive language development, bilateral hearing impairment, and definite mental retardation. The boy had a moderate delay in receptive language skills, had moderate hearing impairment in one ear, and showed mild mental retardation. The father has low-set ears, some deficits in receptive language skills, is illiterate, and was found to be borderline mentally retarded. The mother and younger child do not have the translocation and are normal in terms of phenotype, intellect, and verbal skills. The accumulating evidence suggests that balanced translocations are associated with an increased frequency of intellectual deficit and congenital anomalies, and the cytogenetic mechanism may be that of position effect.