医疗的经济辐射作用

挪威是一个实行市场经济的国家,我们选择了这样的体系是因为它能够有效地解决很多——但不是全部——生产、货物流通以及服务的竞争问题。在发展一个国际化的市场体系的同时,挪威也发展了强大的公共机构和公共服务。一个有效的市场并不意味着我们就不需要公共部门,或者像有些流行观念所认为的,任何公共服务都应该私有化。其实,一个市场是需要严格的监管,需要与公共组织相配合才能良好地运转,而且需要一个广泛覆盖并且有效的公共部门,来补充提供那些市场无法有效而让人满意地提供的服务,比如教育、医疗和环境保护等。但是,这些公共服务不能由…     

Extent of ictal origin in mesial temporal sclerosis patients monitored with subdural intracranial electrodes predicts outcome.

In patients with mesiotemporal sclerosis, posterior hippocampal involvement at the ictal onset is not associated with an excellent outcome. A study confirmed that ictal onset in the posterior parahippocampal gyrus is associated with a less favorable outcome compared with ictal onset in the anterior parahippocampal gyrus in patients with mesiobasal temporal lobe epilepsy who are undergoing foramen ovale recording. The authors hypothesized that involvement of the two medial contact points of posterior basal temporal subdural (SD) strip at the ictal onset, representing ictal onset in the posterior parahippocampal gyrus, may also adversely influence the surgical outcome. With this objective, the authors assessed the incidence of posterior basal temporal SD strip (the two medial contact points) involvement at the ictal onset in patients with mesiotemporal sclerosis and determined whether presence of this finding influenced surgical outcome. Thirty-six patients with mesiotemporal sclerosis underwent a single SD grid (lateral frontotemporal) and strips (three basal temporal and one orbitosubfrontal) monitoring. Based on the earliest involvement of basal temporal strips (the two medial contact points) during the seizure, patients were classified into (1) anterior and/or middle basal temporal, or (2) posterior basal temporal (with or without involvement of anterior and/or middle basal temporal) ictal onset groups. A temporal lobectomy with adequate resection of the ictal onset zone was performed in all patients. Surgical outcome was based on Engel's classification. Six of 36 (17%) patients were classified into the posterior basal temporal ictal onset group. Only two patients from the posterior basal temporal ictal onset group experienced a good outcome compared with 26 of 30 patients from anterior and/or middle basal temporal ictal onset group (P = 0.01). In patients with mesiotemporal sclerosis who were monitored with SD electrodes, involvement of the two medial contact points of posterior basal temporal strip at the ictal onset (representing ictal onset in the posterior parahippocampal gyrus) occurred in 17% of the patients. These patients might not experience an excellent surgical outcome despite including the ictal onset zone in resection. These findings may be useful in presurgical counseling of patients with mesiotemporal sclerosis who undergo intracranial SD monitoring.     

HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels.

The persistent infection of human glial cells with HIV-1 is characterized by prominent expression of the Nef protein. In order to evaluate the possible role of Nef in the development of HIV-1-associated neurological disorders, we compared Nef with known neuroactive proteins. We found that HIV Nef shares sequence and structural features with scorpion peptides known to interact with K+ channels. Sequence similarity encompasses two distinct regions of scorpion peptides. Based on crystallography data, both regions in scorpion peptides cooperate in forming a common domain stabilized by ion pairs between charged amino-acid residues. Recombinant Nef protein, as well as a synthetic part of a scorpion channel active peptide (M10), reversibly increased the total K+ current of chick dorsal root ganglions in patch-clamp experiments without killing the cells. These results indicate that a region conserved in HIV Nef and scorpion peptides concurs in both structure and electrophysiological activity and suggest that Nef, like scorpion peptides, may affect neuronal cell function.     

Addition von Nucleophilen an 5-Desazaflavine,Teil 1

Addition of Nucleophiles to 5-Deazaflavins, Part 1 The reactivity of 5-deazaflavins and 5-deazaflaviniumsalts againts nucleophiles such as hydride-, dithionite-, sulfite- and cyanide ions as well as carbanions is described. The addition takes place in the 5-position and is in much cases reversible with acid. The title-compounds behave, as shown in photoreactions⁵), as “flavin-shaped nicotinamide models”. Side reactions and reoxidation of the adducts are discussed.     

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.     

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases.

The aim of the present study was to explore cell biological characteristics of normal breast, benign proliferative breast diseases and noninvasive breast malignancies based on the recently published adult progenitor cell concept from our group. Here, we investigated the proliferative activity of CK5/14(+), CK8/18/19(+) and alpha-smooth muscle actin(+) cellular phenotypes encountered in normal mammary gland, in a series of usual ductal hyperplasias and early malignant breast diseases, such as atypical ductal and lobular hyperplasias, as well as ductal and lobular in situ carcinomas. Immunohistochemical double labeling was performed on frozen sections from diagnostic breast biopsies by using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast tissues and usual ductal hyperplasias were characterized by a heterogeneous cellular composition of the growth fraction. The proliferative cell compartment consisted of CK8/18/19(+) glandular and, in a variable proportion, CK5/14(+) progenitor phenotypes. In contrast, noninvasive breast malignancies were composed of a monotonous proliferation of CK 8/18/19(+) neoplastic glandular cells. These findings indicate a significant role of progenitor cells in the development of benign proliferative breast diseases and lend support to the view that malignant transformation in the human breast usually occurs in a cell committed to the glandular lineage. Our results provide cell kinetic support to the functional progenitor cell hypothesis, and we propose this concept as an operative model for understanding benign proliferative and malignant breast diseases.     

Chromosomal imbalances in clear cell ependymomas.

Clear cell ependymoma is a rare and diagnostically challenging subtype of ependymoma, whose genetic features are essentially unknown. We studied 13 clear cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by comparative genomic hybridization (CGH). Chromosomal imbalances were found in 12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3 (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%), as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO grade III samples (1.4 vs 3.5 per case). Although some of the implicated chromosomes have previously been shown to be involved in other ependymoma variants, the striking frequency of +1q, -9, and -3 suggests that aberrations differ between clear cell and other types of ependymomas, in particular, for loss of chromosome 9 which can be regarded as the molecular hallmark of clear cell ependymomas.     

Tetrahydrobiopterin Attenuates Microvascular Reperfusion Injury Following Murine Pancreas Transplantation

In this study we investigated the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, on ischemia-reperfusion injury (IRI) following murine pancreas transplantation. Pancreatic grafts were exposed to prolonged cold ischemia times (CIT) and different treatment regimens: normal saline (S), S + 16 h CIT, BH4 50 mg/kg + 16 h CIT. Nontransplanted animals served as controls. Graft microcirculation was analyzed by means of functional capillary density (FCD) and capillary diameters (CD) after 2 h reperfusion using intravital microscopy. Quantification of inflammatory responses (mononuclear infiltration) and endothelial disintegration (edema formation) was done by histology (hematoxylin and eosin), and peroxynitrite formation assessed by nitrotyrosine immunostaining. FCD was significantly reduced after prolonged CIT, paralleled by increased peroxynitrite formation as compared with controls (all p < 0.05). Microcirculatory changes correlated significantly with intragraft peroxynitrite generation (Spearman: r = -0.56; p < 0.01). Pancreatic grafts treated with BH4 displayed markedly higher FCD values (p < 0.01) and abrogated nitrotyrosine staining (p = 0.03). CD were not significantly different in any group. Histology showed increased inflammation, interstitial edema, hemorrhage, acinar vacuolization and focal areas of necrosis after 16 h CIT, which was diminished by BH4 administration (p < 0.01). BH4 treatment significantly reduces post-ischemic deterioration of microcirculation as well as histologic damage and might be a promising novel strategy in attenuating IRI following pancreas transplantation.     

Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine

Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)