Functionally intact in vitro preparation generating respiratory activity in neonatal and mature mammals

The present report describes a novel rhythmically active brainstem slice preparation that generates respiratory activity spontaneously in both mice and rats of varying maturational states. The brainstems of neonatal (0–4 days) and mature (3–8 weeks) mice and rats were isolated and a 600- to 750-m thick slice cut to include the dorsomedial and the ventrolateral regions of the complete rostro-caudal extent of the medulla. This plane of section we have termed tilted-sagittal. Rhythmically discharging neurones were recorded extracellularly from both the dorsal and ventral regions of the slice. The recording sites of these neurones were found in the hypoglossal motonucleus (XII) and in areas of the ventrolateral medulla that includes the ventral respiratory group (VRG) region. Histological examination revealed the preservation of neuronal structures important for cardiorespiratory regulation and reflex control including the nucleus of the solitary tract as well as the nucleus ambiguus. In addition, pontine structures including the A5 region were also preserved. Rhythmic activity was found only in slices where the ambiguual column was preserved in its entirety. The mean frequency of discharge of XII neurones was 20 and 10 bursts per minute in neonates and mature rodents respectively. In preparations of mature animals we demonstrate that this frequency increased significantly (P<0.05) by either raising temperature from 29°C to 38°C (54%), elevating extracellular potassium concentration from 4 to 7.5 mM (52%), blocking potassium channels (20%) or decreasing pH from 7.4 to 7.0 (18%). The burst duration to frequency ratio of XII and VRG rhythmic neurones was similar and therefore indicative of a common brainstem oscillator. Consistent with this finding was that rhythmic activity in the VRG persisted despite removal of the dorsomedial region of the slice. In contrast, rhythmic XII neurones became tonic following mechanical disconnection of the VRG.     

Functional activity of auditory cortex studied with SPECT: methodology validation and application in bilateral profound deafness

To evaluate the differences in the functional activity of the auditory cortex between normal hearing and profound deafness, a perfusion single photon emission tomography (SPECT) study was designed. SPECT stereotaxic localisation of the auditory cortex was previously validated in 2 brains by means of an anatomical study of the macroscopic localisation and cytoarchitecture of the auditory cortex. Additionally, 15 controls with normal hearing and 30 patients with profound bilateral deafness were scanned using external anatomical point sources (glabela, ineon) for stereotaxic location of the auditory cortex. The normal controls were scanned in auditive deprivation and, in 10 cases, during a monoaural tonal stimulation. Cerebral blood flow relative to cerebellum (relCBF) was assessed in the auditory cortex. The anatomical study showed that mean differences between the true auditory cortex size and the measured SPECT value were less than 2.5 mm. Nevertheless, only the caudal aspect of this area corresponded to the primary auditory cortex in the cytoarchitectonic study. During tonal stimulation, control subjects presented a significant increase of relCBF in the auditory cortex bilaterally, with significant differences in the asymmetry index (contralateral to the side of stimulation). The relCBF in the auditory cortex of controls in deprivation conditions was significantly higher than in deaf patients. There were no significant differences between groups of deaf patients, however the highest values were seen after cochlear implant. SPECT is a suitable method for studying changes in auditory cortex activity relative to different functional conditions, with a possible role in cochlear implant candidates in predicting the future benefit of the implantation.     

Relation between concentration of lead, zinc and lysozyme in placentas of women with intrauterine foetal growth retardation

Intrauterine foetal growth retardation (IUGR) implies increased risk of morbidity and mortality of the newborn. Aetiology of intrauterine retardation is probably multifactorial and may include maternal infection, malnutrition, placental dysfunction, hypertension, toxaemia, smoking, professional and environmental exposure. The work concentrates on the lead, zinc and lysozyme levels in blood and placental tissues of 50 females in the IUGR group and 43 females from a control group. Statistically significant differences in zinc and lead levels between the compared group were found. The IUGR group had lower zinc and higher lead levels. A significant negative correlation of zinc and lead levels was observed. We found a statistically significant relationship between lead levels in placental tissues and the age of the pregnant women. Higher age is associated with higher lead levels in placental tissue, whereas zinc levels decrease. In placental tissues of pregnant females of the IUGR group higher lysozyme levels were found. On the basis of the discussed results the authors recommend zinc supplementation during the pregnancy.     

Uveal melanoma: correlation of histopathologic and radiologic findings by using thin-section MR imaging with a surface coil

PURPOSE: To evaluate whether the different signal intensities at magnetic resonance (MR) imaging of melanoma are associated with a higher content of melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range, 30-87 years) with uveal melanoma were compared with histopathologic examination findings obtained after enucleation. MR imaging was performed with 2-mm sections by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and after contrast material administration. RESULTS: In 33 (79%) of the patients, there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively. Quantitative evaluation yielded better results, especially at T1-weighted imaging; an 86% correlation was found. Because of methodological reasons, only the superficial pigmentation of inhomogeneous tumors could be evaluated with ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an accurate prediction of melanomatous pigmentation with quantitative evaluation of plain T1-weighted images and is superior to ophthalmoscopy in cases of inhomogeneous pigmentation.     

Improvement of rat lung structure and function after preservation with celsior

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min of in vitro reperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxygenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.     

Cytoskeleton mediates inhibition of the fast Na+ current in respiratory brainstem neurons during hypoxia

Whole-cell Na+ currents (INa) were recorded in inspiratory neurons in a medullary slice preparation from neonatal mouse that contains the functional respiratory network. Hypoxia and metabolic poisoning with KCN rapidly inhibited INa by reducing the number of Na+ channels available for opening during depolarization. Application of agents specific for G-proteins, protein kinase C and A, intracellular Ca2+ and pH did not prevent the hypoxic inhibition of INa. The effects of hypo-osmolarity and hypoxia were additive, whereas hyperosmolarity partially prevented a subsequent hypoxic inhibition of INa. Cytochalasin B and colchicine decreased, and taxol or phalloidin increased INa and reduced its hypoxic inhibition. We conclude that cytoskeleton rearrangements during hypoxia are responsible for suppression of a fast INa in brainstem respiratory neurons, which could be mediated by the uncoupling of channel inactivation gates from cytoskeletal elements.     

Diagnosis and therapy of spinal stenosis in the elderly

PROBLEM: Spinal stenosis is a common and increasing problem in the elderly population and a diagnostic and therapeutic challenge. METHODS: An overview of etiology, epidemiology, diagnostics and therapy is given based on a literature review of the years 1978-1998 and experiences since 1985. RESULTS: Dealing with spinal stenosis we have to distinguish concerning diagnostics and therapy between cervical and lumbar spinal stenosis. The cardinal symptom of the lumbar spinal stenosis is the claudicatio spinalis and of the cervical spinal stenosis the cervical myelopathy occasionally combined with radiculopathy. The first therapeutic step should be the conservative therapy in nearly all cases, the only exception is a severe cervical myelopathy where an operation is indicated. In case of persistent or progressive symptoms under a sufficient conservative therapy, operative therapy is indicated. The different possible therapy decisions will be based on flow-charts. CONCLUSION: Whereas in lumbar spinal stenosis the indication for operative therapy should be considered with reservation, in cervical spinal stenosis with myelopathy operative therapy should be considered at an early stage.     

Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis

BACKGROUND: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastro-oesophageal reflux disease (GERD). METHODS: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. RESULTS: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night-time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. CONCLUSIONS: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD.     

Volatile constituents of the dried leaves of Cassia angustifolia and C. acutifolia (Sennae folium)

The official drug Sennae folium (obtained from Cassia angustifolia and/or C. acutifolia) was found to contain small amounts of volatiles (0.047% based on dry weight) which were analyzed in detail by GC and GC/MS. More than 200 compounds could be detected, 122 of them were identified, representing about 90.7% of the peak area of the total mixture. The volatile constituents can be classified into monoterpenoids (8.8% for sample A and 34.6% for B), sesquiterpenoids (4.2% and 4.0%, respectively), phenylpropanoids (4.2%/15.2%), fatty acids and esters (54.3%/14.2%), and miscellaneous compounds (19.3%/22.7%). Apart from hexadecanoic acid which was strong in both samples (36.8%/9.7%), the occurrence of menthol, geranylacetone, and (E)-anethole is of interest.