Pneumonia: a deadly disease despite intensive care treatment

In a retrospective study of 30 patients with pneumonia treated in the intensive care unit, it was found that cultures from sputum and bronchial secretions did poorly correspond with blood cultures or serological tests. In only 15 of the patients a reliable etiological diagnosis was ever established. Mechanical ventilation was used in 22 patients, usually with a high oxygen need. At the start of this ventilation a significant blood pressure fall and a further pulmonary deterioration was observed. In fatal cases this pulmonary dysfunction was progressive. The overall mortality was 47%. When an FI02 above 0.6 was needed in the ventilator the mortality was 13/14 (93%).     

Wear of the Christiansen hip prosthesis

The wear was examined in 39 Christiansen total hip prostheses, which were removed because of mechanical loosening after being used 5 (3-11) years. In the polyacetal acetabular cups, the head had made an eccentric defect, the mean volume of which was 680 (180-3310) mm³. The mean penetration of the head into the wall of the cup was 0.8 (0.1-3.2) mm. In two additional cups the head had penetrated right through the wall of the cup. In three prostheses the polyacetal sleeve of the trunnion was so worn that the head bore directly on the stem. There was a positive correlation between wear and the time the prostheses had been used before symptoms of loosening presented.     

Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

A clinical comparison of the Laryngeal Tube™ and the Laryngeal Mask™ in spontaneously breathing anesthetized patients

Abstract: Background: The laryngeal mask airway (LMA) can be used in general anaesthesia without neuromuscular block. The laryngeal tube (LT) is a new airway device with similar airway features as LMA. LT is provided with a distal cuff to prevent regurgitation. In this study we compared the LMA and LT concerning patient and user aspects. Methods: Sixty patients with ASA (American Society of Anestesiologists) score 1–2 scheduled for minor surgery were randomized to be ventilated either through LMA or LT. After insertion, the number of insertion attempts, and “positioning” and “airway-assessment” was evaluated. The patients reported on “sore throat” after 30 and 60 minutes and the day after anaesthesia. Results: Gender and mean age were equal in both groups. The first insertion attempt was successful in 25 of 28 patients randomised to LMA and in 23 of 27 patients randomised to LT. LMA was evaluated to be easier in “positioning” whereas no difference in “sore throat” was reported. Conclusion: We found no difference between the LMA and the LT in terms user and patient friendliness and safety.     

Regulation of G-PROTEIN mRNA abundancy and cAMP accumulation after long-term opioid incubation in primary cultures of astroglia from the rat cerebral cortex.

Primary astroglial cultures were incubated with delta (10(-6) M DPDPE) or kappa (10(-5) M U-50,488H) receptor agonists for 5 days. Thereafter, the acute inhibitory actions of delta or kappa receptor agonists on forskolin stimulated cAMP accumulation were assayed. The G alpha s, G alpha i-1 and G alpha i-2 mRNA levels were quantified after 5 days of either delta or kappa receptor agonist treatment using a solution hybridization, RNase protection assay. Pronounced effects were observed after 5 days of kappa receptor agonist [10(-5) M U-50,488H] incubation. This treatment resulted in an attenuation in the acute inhibitory action of delta and kappa receptor agonists. Furthermore, a decreased stimulatory action of forskolin was seen. Similar effects were also seen after delta receptor stimulation. We also investigated the effects after 24 h and 3 days of incubation with the kappa receptor agonist (10(-5) M) U-50,488H. The 24 h incubation resulted in a decreased sensitivity to the acute inhibitory action of delta and kappa receptor agonists in the astroglial cultures. This effect was further accentuated after the 3 days of incubation with 10(-5) M U-50,488H. No significant change was seen in the basal accumulation of cAMP after incubation with the kappa agonist U-50,488H. However, after 5 days of incubation with the delta agonist DPDPE, a significantly increased basal accumulation of cAMP was seen in the astroglial cultures. After 5 days of delta or kappa agonist incubation, an increase in G alpha s mRNA level and a decrease in G alpha i-2 mRNA level was seen compared with controls. No statistically significant alterations in the amount of G alpha i-1 mRNA were seen. The data obtained in the present study indicate that the effects of long-term opioid treatment alters the sensitivity of glial cell opioid receptors. Furthermore, long term opioid treatment induces alterations in glial G-protein mRNA levels.     

Contrast agents in functional MR imaging

Contrast agents have greatly expanded the role of MR imaging (MRI) to allow assessment of physiologic, or “functional,” parameters. Although activation mapping generally does not require contrast agents, other forms of functional MRI, including mapping of cerebral hemodynamics (eg, perfusion imaging), are best done with the use of contrast agents. Serial echo planar images are obtained after bolus injection of lanthanide chelates. Application of susceptibility contrast physics and standard tracer kinetic principles permits generation of relative cerebral blood volume maps. Deconvolution of cerebral blood flow and mean transit time parameters is also possible within technical limitations. By using diffusion and perfusion pulse sequences, an imaging correlate to the ischemic penumbra can be identified. Functional MRI perfusion imaging of intraaxial tumors is analogous to positron emission tomography for delineation of metabolic activity, yet may be even more sensitive to neovascularity and possesses improved image quality. Clinical applications include biopsy site selection and postirradiation follow-up. Further improvements in data analysis and map generation techniques may improve diagnostic accuracy and utility.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Very old people’s use of the pedestrian environment: functional limitations, frequency of activity and environmental demands

Due to decreased functional capacity as well as high environmental demands there is a risk of diminishing activity outside home in very old age (age 80+). In order to explore differences according to functional limitations (FL) among very old people with respect to frequency of activity, perceived health, overall perception of neighbourhood environment, and perceived problems in the pedestrian environment, data derived from a postal questionnaire survey to very old people living in an urban area in Sweden were used. This explorative study is based on the sub-sample of people aged 80+ who reported outdoor activities (n = 97). Four groups of respondents with different types of FL were identified: with no FL (n = 23), with only movement-related FL (n = 26), with only perception/cognition-related FL (n = 16), and with both movement- and perception/ cognition-related FL (n = 32). The majority of the respondents reported rather high frequency of activity outside home. When examining differences between the four groups, the analysis indicated how the complexity of FL and perceived problems in the pedestrian environment impacted on their activity performance. Persons with both movement- and perception/cognition-related FL were less satisfied with their frequency of activity, experienced their health more negatively and experienced more problems in the pedestrian environment than in the other groups. The findings from this study indicate the importance of considering combinations of FL in creating supportive environments for activity and health.     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.