Immunoglobulins in chronic alcoholics: relation to liver histology and effect of 2-month abstinence therapy.

Serum immunoglobulin levels and alpha1-fetoprotein were measured in 49 male alcoholics entering an abstinence program. These parameters were evaluated in relation to liver histology. Of 49 studied alcoholics, 32 had elevated serum immunoglobulin levels, chiefly IgA, which occurred in 29 patients. IgA elevation was also observed in patients with normal histological picture of the liver. Of 17 alcoholics with normal immunoglobulin levels, in 9, i.e. 53%, liver histology was normal. In the group of 32 alcoholics with elevated immunoglobulin levles, normal liver histology was encountered only in 8 patients, i.e. 25%. Two-month abstinence in 18 alcoholics with previously elevated IgA levels caused their decrease in 12 patients, i.e. 66%. A decrease in IgA was noted even in patients with symptoms of histological worsening. Of 49 alcoholics, only 1 showed significantly elevated alpha1-fetoprotein.     

Impact of histological subtype on survival of patients with surgically-treated stage IA2-IIB cervical cancer: Adenocarcinoma versus squamous cell carcinoma

Objectives

To evaluate the significance of adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) with regard to the survival of surgically-treated early stage cervical cancer patients.

Methods

We retrospectively reviewed the medical records of 520 patients with FIGO stage IA2-IIB cervical cancer who were treated with radical hysterectomy with or without adjuvant radiotherapy between January 1998 and December 2008. The patients were classified according to (i) pathological risk factors (low-, intermediate-, or high-risk group) and (ii) adjuvant radiotherapy (concurrent chemoradiotherapy [CCRT group] or radiotherapy alone [RT group]). Survival outcomes were examined by Kaplan-Meier method and compared with Log-rank test. Multivariate analysis for disease-specific survival (DSS) was performed using Cox proportional hazards regression model to investigate the prognostic significance of histological subtype.

Results

AC histology was associated with significantly decreased DSS compared with SCC histology in the intermediate- and high-risk groups (hazard ratio: 3.06 and 2.88, respectively, both P < 0.05) while there was no survival difference in the low-risk group (P = 0.1). Among patients who received any types of adjuvant radiotherapy, DSS of AC histology patients were significantly poorer than SCC histology. Multivariate analysis demonstrated AC histology to be an independent predictor of decreased DSS in both CCRT and RT groups. Moreover, pelvic nodal metastasis significantly predicted the poor survival of patients with AC histology who received CCRT in multivariate analysis

Conclusions

Adenocarcinoma is an independent prognostic indicator of poor survival in early stage cervical cancer patients with intermediate- and high-risk factors, regardless of the type of adjuvant radiotherapy after radical hysterectomy.     

High-density lipoproteins can act as carriers of glycophosphoinositol lipid-anchored CD59 in human plasma.

CD59 (protectin) is a glycophosphoinositol (GPI) lipid-anchored inhibitor of complement lysis that is expressed on the membranes of blood cells, endothelial cells, epithelial cells and cardiomyocytes. CD59 may be shed from cell surfaces, e.g. during cell injury, but when entering human plasma its fate is unknown. In this study we observed that radiolabelled lipid-anchored CD59, but not soluble urinary CD59 without anchor lipid, incorporated into high-density lipoprotein (HDL) particles when mixed with human serum and analysed by high resolution gel filtration and anti-apoA-I affinity chromatography. Only a small proportion of CD59 entered the low-density lipoprotein (LDL) fraction. HDL particles were capable of incorporating 25-42% of [125I]CD that was preinserted into the membranes of rabbit erythrocytes (RaE) and transferred 7-14% of [125I]CD59 back to RaE or to cultured human endothelial cells (EA.hy 926). Immunoaffinity purification and immunoblotting analysis demonstrated that HDL isolated from normolipidemic human serum contained small amounts of CD59. These results suggest that HDL particles could be involved in the recycling of GPI lipid-anchored molecules released from cell surfaces.     

Effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT—phantom study

Background

CT optimization has a special importance in children. Smaller body size accentuates the importance of patient positioning affecting both radiation dose and image quality.

Objective

To determine the effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT examination.

Materials and methods

Chest scans of a pediatric 5-year anthropomorphic phantom were performed in different vertical positions (?6 cm to +5.4 cm) with a 64-slice CT scanner. Organ doses were measured with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Image noise and contrast were determined from the CT number histograms corresponding to different tissues.

Results

Significant changes in organ doses resulting from vertical positioning were observed, especially in radiosensitive anterior organs. The breast dose increased up to 16% and the thyroid dose up to 24% in lower positions. The noise was increased up to 45% relative to the centre position in the highest and lowest vertical positions, with a particular increase observed on the anterior and posterior sides, respectively. Off-centering also affected measured image contrast.

Conclusion

Vertical off-centering markedly affects organ doses and measured image-quality parameters in pediatric chest CT examination. Special attention should be given to correct patient centering when preparing patients for CT scans, especially when imaging children.     

Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM)

For evaluation of the degree of senescence in SAM-P, accelerated senescence prone mouse, formerly called SAM or prone series or P-series, consisting of SAM-P/1, SAM-P/2, SAM-P/3 and SAM-P/4 corresponding to P-1, P-2, P-3 and P-4 series, respectively, in the previous reports, and in SAM-R, accelerated senescence resistant mouse, formerly called resistant series or R-series, consisting of SAM-R/1, SAM-R/2 and SAM-R/3 corresponding to R-1, R-2 and R-3 series, respectively, in the previous reports, the grading score system was adopted. The items to be examined in this system include 11 categories selected from the clinical signs and gross lesions considered to be associated with the aging process. The degree of the senescence in each category was graded from 0 to 4 according to the detailed criteria devised in our laboratory. After 8 months of age each mouse was examined every 4 months, and some of the mice were examined after 2 months of age.In almost all categories, the grading score and incidence began to increase from 4 or 6 months of age and continued to increase with advancing age in both SAM-P and SAM-R. The increase, however, was more marked in SAM-P than in SAM-R. The slow but steady increase in the SAM-R levelled out at 24 months of age and was comparable to that of 12 months of age in SAM-P. In both SAM-P/1 at 8 months of age and SAM-R/2 at 12 months of age, there was a significant reverse correlation between total score of this grading score system and length of residual life after examination.Systematic and extensive studies using the grading score system showed that if the validity of the system is, based on “irreversibility” and “universality” of the changes in     

Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting with oculomotor nerve palsy

Introduction

Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has been extremely poor, recently, the first prospective study for ATRT demonstrated improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in children and the most frequent etiology is congenital. To our knowledge, only a few ATRT cases presenting with oculomotor nerve palsy have been reported, but ATRT originating from the cavernous sinus (CS) has not yet been reported.

Case report

An 18-month-old girl with right oculomotor nerve palsy was admitted, and a small mass in the right CS was detected with brain MRI. Although she received steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge. One month after admission, the mass was partially resected and diagnosed as ATRT. Multimodal therapy including anthracycline-based chemotherapy, intrathecal therapy, and cranial irradiation was performed. Twenty-nine months after resection, she was alive without tumor relapse, but the oculomotor nerve palsy persisted.

Conclusion

This is the first reported case of ATRT located in the CS presenting with oculomotor nerve palsy. This case was successfully treated with partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X-ray irradiation.     

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open‐label, single‐arm study of IVIG in immunoglobulin (Ig)‐naïve or IVIG pre‐treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double‐blind, randomized study including an open‐label, single‐arm IVIG phase in IVIG pre‐treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre‐treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was ?1.0 (interquartile range ?2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score . In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA‐approved IVIG for CIDP, in a population of mainly pre‐treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].     

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by <Superscript>18</Superscript>F-FDG

Objective

One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals.

Methods

A radiotracer for glucose, ¹⁸F-2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316,243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. ¹⁸F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography.

Results

In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin, while the responses were inhibited in the adipose tissues of Wistar fatty rats.

Conclusion

A system to monitor tissue glucose uptake with ¹⁸F-FDG enabled us to detect clear differences in basal glucose uptake between disease-model animals and their corresponding controls. The responses in the tissues to insulin or β3 agonist could be identified. Taken as a whole, the biodistribution method with ¹⁸F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals.

     

Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis

Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients’ writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.