Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Investigations on organ-specific metabolism and genotoxic effects of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine (BCPN) and its analogs N-nitrosodibutylamine (NDBA) and N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA)

N-Nitrosodibutylamine (NDBA) and its omega-oxidized metabolites N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA) and N-nitrosobutyl-3-carboxypropylamine (BCPN) are potent urinary bladder carcinogens. To study putative organ specific activation of BCPN, its alpha-oxidation by liver and urinary bladder microsomal fractions was investigated in comparison to NDBA and 4-OH-NDBA. Additionally, induction of DNA single strand breaks (SSB) was monitored in hepatocytes and in a human lymphoblastoid cell line (Namalva) in the presence and absence of external metabolic activation, including N-nitroso-t-butyl-n-butylamine as a negative control. BCPN was alpha-hydroxylated and dealkylated at both alkyl chains in small rates (about 1 nmol x mg protein-1 x 60 min-1) by microsomes from rat liver and pig urinary bladder epithelium. NDBA and 4-OH-NDBA were dealkylated at similarly low rates by pig urinary bladder microsomes, in strong contrast to the high debutylation rates observed for rat liver microsomes. Correspondingly, SSB induction by NDBA and 4-OH-NDBA was observed in Namalva cells with NDBA and 4-OH-NDBA in the presence of PB-induced rat liver microsomes but not with urinary bladder microsomes or without external activation. BCPN did not induce DNA-damage in Namalva cells (with or without external activation) or in rat hepatocytes. Significant induction of sister chromatid exchanges (SCEs) and micronuclei, however, was observed in Namalva cells after incubation with NDBA and BCPN. Our data suggest activation of BCPN via alpha-oxidation in the urinary bladder, even though activation rate in-vitro is so low that a positive response is not detectable by several short-term tests.     

Qualität der postoperativen Schmerztherapie

Many patients still suffer from unnessesary pain in the postoperative period. Waiting for new technologies or drugs will not improve the status of acute pain management. The establishment of an acute service is needed to reduce the incidence of postoperative pain. Acute pain therapy is one of the great challenges we have to take up.     

科室主任管理职能与基本素质探讨

人力资源在管理中发挥着重要作用，其中，科室主任作为医院人力资源的重要组成部分，在医院惯性运行和可持续发展中扮演着重要角色。因此，科室主任因其技术和管理双重职责所具备的管理职能、基本素质和领导艺术在日常工作中显得尤为关键。     

Targeted gene disruption of murine CD7

CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig superfamily. CD7 is a marker of mature human T cells and NK cells, and is expressed early in their development. Cross-linking CD7 positively modulates T cell and NK cell activity as measured by calcium fluxes, expression of adhesion molecules, cytokine secretion and proliferation. CD7 associates directly with phosphoinositol 3'-kinase, and CD7 ligation induces production of D-3 phosphoinositides and tyrosine phosphorylation. Severe combined immunodeficiency has been associated with a lack of lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog is encoded by a single gene on chromosome 11. In order to characterize the role of CD7 in lymphocyte development and function we have eliminated the CD7 gene by targeted disruption. CD7- deficient mice display normal histology of thymus and spleen, normal lymphocyte populations in primary and secondary lymphoid tissues, and normal serum Ig levels. Specific antibody responses after immunization with T-dependent and T-independent antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient lymphocytes respond normally to T cell mitogenic and allogeneic stimuli, and display normal NK cell cytotoxicity.      

Ocular counterroll modulates the preferred direction of saccade-related pontine burst neurons in the monkey

Saccade-related burst neurons in the paramedian pontine reticular formation (PPRF) of the head-restrained monkey provide a phasic velocity signal to extraocular motoneurons for the generation of rapid eye movements. In the superior colliculus (SC), which directly projects to the PPRF, the motor command for conjugate saccades with the head restrained in a roll position is represented in a reference frame in between oculocentric and space-fixed coordinates with a clear bias toward gravity. Here we studied the preferred direction of premotor burst neurons in the PPRF during static head roll to characterize their frame of reference with respect to head and eye position. In 59 neurons (short-lead, burst-tonic, and long-lead burst neurons), we found that the preferred direction of eye displacement of these neurons changed, relative to head-fixed landmarks, in the horizontal-vertical plane during static head roll. For the short-lead burst neurons and the burst-tonic group, the change was about one-fourth of the amount of ocular counterroll (OCR) and significantly different from a head-centered representation. In the long-lead burst neurons, the rotation of the preferred direction showed a larger trend of about one-half of OCR. During microelectrical stimulation of the PPRF (9 sites in 2 monkeys), the elicited eye movements rotated with about one-half the amount of OCR. In a simple pulley model of the oculomotor plant, the noncraniocentric reference frame of the PPRF output neurons could be reproduced for recently measured pulley positions, if the pulleys were assumed to rotate as a function of OCR with a gain of 0.5. We conclude that the saccadic displacement signal is transformed from a representation in the SC with a clear bias to gravity to a representation in the PPRF that is closely craniocentric, but rotates with OCR, consistent with current concepts of the oculomotor plant.     

Monosomy 7p in meningiomas: a rare constituent of tumor progression

We present karyotypes of 15 meningiomas with structural aberrations of chromosome 7, which were taken from a consecutive series of 400 cytogenetically characterized meningiomas. Twelve of these tumors (80%) displayed partial or complete monosomy 7p with a consensus deleted region of 7p12 approximately pter, in 6 of 15 cases arising from an unbalanced whole-arm t(1;7)(q11;p11), and in 4 of 15 cases from a whole-arm translocation involving other chromosomes. Other types of partial aneusomy 7 (3/15 cases) or balanced aberrations of chromosome 7 (2/15 cases) were relatively rare. In most cases (11/15), the centromeric region of chromosome 7 was involved in the rearrangements. We conclude that in meningiomas, the near-centromeric region of chromosome 7 is particularly prone to structural rearrangements most frequently resulting in monosomy 7p. The investigation of the histopathologic features of this rare cytogenetic subgroup of meningiomas showed no clear genotype/phenotype correlation. As 7 of 11 of the meningiomas with monosomy 7p belonged to World Health Organization grades II or III, which usually comprise less than 20% of all meningiomas, partial loss of 7p appears to be involved in tumor progression in meningiomas. Because monosomy 7p is typically associated with the strongly progression-associated monosomy 1p, however, monosomy 7p represents a cofactor more than a stand-alone feature of meningioma progression.     

Visual-vestibular interaction in the flocculus of the alert monkey

Summary The activity of Purkinje cells (P-cells) was recorded in the flocculus of alert Rhesus monkeys under different conditions of visual-vestibular stimulation. Stimulus conditions were vestibular, optokinetic, combined and conflicting. About 10–20% of all P-cells were activated in their simple spike activity during conflicting stimulation to the recording side (type I) and gave no response or much less during vestibular stimulation. About half of these P-cells were also activated during optokinetic stimulation to the recording side at velocities above 40–60 deg/s. Simple and complex spike activity behaved in a reciprocal way with overlapping but not identical working ranges. Simple spike modulation was unidirectional, complex spike activity always bidirectional. Modulation of simple spike activity cannot be related to one single parameter of the sensory input or the oculomotor output. The hypothesis is put forward that the vestibular nuclei and the flocculus behave in a complementary fashion in processing visual-vestibular information, the flocculus being specialized for high velocity optokinetic nystagmus and suppression of vestibular nystagmus.Supported by a grant from the Swiss National Foundation for Scientific Research 3.343-2.78