Activated microglia do not mediate the early deposition of Abeta in carriers of the apolipoprotein Eepsilon4 allele

Activated microglia are a prominent component of the senile plaques in end-stage Alzheimer's disease, but whether microglia contribute to the initiation of the lesions remains unknown. In a previous postmortem study of non-demented elderly cases, we found that amyloidogenesis is advanced by at least 10 years in carriers of the apoEepsilon4 allele. To determine whether microglia are involved in the initial stages of beta-amyloid pathogenesis and whether apoE genotype influences microglial activation, we quantified HLA-DR-immunoreactive microglia in the medial temporal lobe of 229 non-demented humans of various APOE genotypes who had died between 50 and 91 years of age. Our results show that the number of HLA-DR-immunoreactive microglia increases with advancing age in both the gray matter and the white matter. In contrast to amyloid plaques and neurofibrillary tangles, there is no significant correlation between apoE genotype and density of microglia, although apoEepsilon4 homozygotes tended to have more microglia than did other apoE groups. In sections double-immunostained for Abeta and activated microglia, activated microglia were associated with dense-cored plaques but not with diffuse plaques, suggesting that microglial activation is a relatively late event in the genesis of beta-amyloid. Activation of microglia thus appears not to be the initial impetus for Abeta-deposition in the elderly.     

Brain uptake of myoinositol after exogenous administration

An acute increase in plasma tonicity results in an adaptive increase in brain organic osmolyte content, but this process requires several days to occur. Slow reaccumulation of brain organic osmolytes may contribute to osmotic demyelination. It was investigated whether administration of intravenous myoinositol in rats could speed entry of the osmolyte into the brain. Two groups of animals were studied: normonatremic animals and animals with hyponatremia (105 mmol/L) of 3-d duration. Animals were intravenously administered either 1 M NaCl to induce a 25 to 28 mM increase in serum sodium concentration over 200 min or an infusate that maintained serum sodium concentration. In some animals, myoinositol was administered intravenously over the same time period to raise plasma myoinositol levels by 5 to 10 mM. Brain myoinositol, electrolyte, and water contents were determined at the end of the infusions. In both normonatremic and hyponatremic rats, infusion of hypertonic saline without myoinositol or infusion of myoinositol without hypertonic saline did not increase brain myoinositol levels above control levels. In normonatremic animals, concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol levels by about 50% above control levels. Brain myoinositol content in animals with uncorrected hyponatremia was about 50% of that found in normonatremic controls; concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol to levels similar to those found in normonatremic controls. Intravenous infusion of myoinositol did not alter brain water content compared with animals not infused with myoinositol. In conclusion, systemic infusion of myoinositol can rapidly increase brain myoinositol content, but only when plasma tonicity is concomitantly increased.     

Neuroblastomas treated at the four major child oncologic clinics in Denmark 1943-1980: an evaluation of 180 cases

One hundred and eighty cases of neuroblastomas from the four child oncology clinics are reviewed. The overall cure rate was 24%. During the 38-year period, there was a significant increase in survival from 0% during the period of 1943-1950 to 32% during the period of 1971-1980. This improved survival rate is most likely a result of adjuvant chemotherapy. Forty percent of the patients appear chronically ill, which reflects the fact that nearly 60% have metastases when they are first seen. In localized disease (stages I-II), the prognosis was favourable (cure rate 69%), while the prognosis for disseminated disease (stage III-IV) was poor (cure rate 5%). A favourable outcome was seen in patients under 1 year (survival rate 46%), and in patients with primary tumours located in the neck or mediastinum (survival rate 48%). When related to stage, however, the survival rates for the former tumours were not significantly better in patients below 1 year or in patients with cervical or thoracic tumours. As is the case in other studies, we found that survival is significantly poorer in males.     

Role of sonography in post-therapeutic control of tumors of the head and neck area

During a 3 year period 572 high-resolution sonograms were carried out in the follow-up examinations of 348 patients who had been treated for ENT malignancy. Our experiences in routine application of this diagnostic method are described and illustrated by typical sonograms. Ultrasound findings of complications (chylous cysts, seromas, granulomas, fistulae) are demonstrated and the value and limitations of sonography in detecting lymph node metastases and primary recurrences are pointed out. In spite of the high accuracy of this method, it is not possible to differentiate between lymph nodes which are invaded by tumour and those with non-specific lymph adenopathy by echographic criteria only. We used ultrasound for follow-up studies on patients treated by irradiation or chemotherapy. Finally, sonography provided additional information on the exact site and size of the tumor. Real-time sonography is not time-consuming and can be applied without any special preparation of the patient. It has therefore become a satisfactory diagnostic method in the follow-up of patients who have undergone treatment of malignant tumors.     

Surgical indications status in ileus using a simple clinical index

Based on a retrospective analysis of a group of patients with ileus disease in regard of the indication for operative intervention an "ileus index" was created which is derived from simple clinical and radiological findings and laboratory data. Prospective evaluation of this index showed its effectiveness in separating patients who had to undergo an emergency operation from those who could be operated electively after preceding diagnostic procedures or could be treated conservatively.     

Is frontal lobe involved in the generation of auditory evoked P50?

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.     

Economics of the antithymocyte globulins Thymoglobulin and Atgam in the treatment of acute renal transplant rejection

OBJECTIVE: To evaluate the economic implications for transplant centres, Medicare and society of treatment of corticosteroid-resistant Banff Grades I, II and III acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin or Atgam. DESIGN AND SETTING: This was a cost analysis of a randomised double-blind multicentre clinical trial comparing the safety and efficacy of Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to 1996. PATIENTS AND PARTICIPANTS: The study enrolled 163 patients, 82 in the Thymoglobulin arm and 81 in the Atgam arm. METHODS: Estimates of the cost of care from the initiation of rejection therapy to 90 days post-therapy were derived from various publicly available sources and applied to patient-specific clinical events documented in the clinical trial. Patients received either intravenous Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15 mg/kg/day) for an average of 9.7 days. RESULTS: On average, Thymoglobulin provided significant cost savings compared with Atgam from the perspective of society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254], Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087; 95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin was primarily due to savings from fewer recurrent rejection treatments and less frequent return to dialysis. CONCLUSIONS: Treatment of acute renal transplant rejection with Thymoglobulin is a cost saving strategy when compared with treatment with Atgam.     

Long-term stability of PBCA nanoparticle suspensions

In this study, the stability of poly(butyl cyanoacrylate) (PBCA) nanoparticle suspensions was examined for up to 1 year by measuring the nanoparticle sizes. The nanoparticles were prepared with different stabilizers (dextran 70.000, poloxamer 188, or polysorbate 85), and the particle size was determined before and after purification by centrifugation and after dilution with different solutions (0.1 N HCl, 0.01 N HCl, H2O, and PBS). The most constant sizes were with the untreated acidic nanoparticle suspensions. In all other cases, agglomeration of the particles occurred: the extent of this agglomeration and the time at which the agglomeration occurred depended on the experimental conditions. Nanoparticle polymer degradation, as indicated by size decrease, was not observed. Thus, PBCA nanoparticles can be stored as suspensions, making the lyophilization and the sometimes problematic resuspension by ultrasonication, unnecessary, which is advantageous for clinical applications.