Ectopic ACTH syndrome associated with large cell neuroendocrine carcinoma of the thymus

A 38-year-old man was admitted for evaluation of Cushing's syndrome. Physical findings showed swelling of the face, and hypertension, but not Cushingoid stigmata. Laboratory data revealed serum cortisol level of 34.1 μg/dL and plasma ACTH of 140 pg/mL. Overnight administration of 1 and 8 mg dexamethasone did not suppress plasma ACTH or serum cortisol. Chest X-ray showed a mass at the upper-anterior quadrant of the mediastinum, and chest CT scan revealed a heterogenous tumor of approximately 60 mm in diameter, which infiltrated into the superior vena cava and ascending aorta, and caused superior vena cava syndrome. The tumor was resected. Histological examination indicated large cell neuroendocrine carcinoma of the thymus and positive immunoreactivity for ACTH. Ten days after the operation, the plasma ACTH decreased as low as 13.7 pg/mL. The present study indicates that large cell neuroendocrine carcinoma of the thymus can cause superior vena cava syndrome and ectopic ACTH syndrome.     

Functional disturbance of the stress-adaptation system in patients with scleroderma

There have been several reports indicating the association between recent stress experiences and the onset or the exacerbation of rheumatic diseases, although few such reports exist in patients with scleroderma (SSc). The present study was performed to elucidate whether there were any functional disturbances in the neuro-endocrine-immune system as a homeostatic system upon stress in SSc patients. Various serum levels of stress-related hormones and cytokines were examined before and after a mental calculation stress test, and a basal questionnaire study of sense of coherence (SOC, which is related to the ability to cope with stress), recent stress experiences, and quality of life (QOL) was performed in 17 SSc patients and in 38 healthy volunteers. Physical QOL state was impaired in patients, but there were no differences in recent stress experiences and SOC scores between patients and controls. Basal serum cortisol levels were similar in patients and controls, but increased levels of proinflammatory cytokine and noradrenalin were seen in SSc patients. Characteristically, contrary to the control group, whose cortisol levels increased significantly following the mental calculation stress test, no significant increase was observed in the patients when post-test cortisol levels were compared to pre-test levels, suggesting a defect in the normal cortisol response upon stress in SSc patients. The present results suggest that there may be impaired function of the neuro-endocrine-immune system upon stress in SSc patients.     

Case of microscopic polyangiitis and giant cell arteritis after influenza vaccination

We report a case of microscopic polyangiitis (mPA) and giant cell arteritis (GCA) (polyangiitis overlap syndrome) after influenza vaccination. A 67-year-old female with chronic kidney disease, who had been observed by a physician, presented fever and headache after immunization of influenza vaccine. She was diagnosed as having with mPA and GCA based on symptoms, worsening of renal function, biopsy of temporal artery (giant cell arteritis) and skin (microscopic polyangiitis), pulmonary involvement and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). She was treated with prednisolone (PSL) and the symptoms were improved. However, two months later she was presented with general physical weariness. She was diagnosed as having with pneumocystis pneumonia, cytomegalovirus infection and cryptococcosis. Despite intensive treatment, she was died and autopsy was performed. The present case suggests that the influenza vaccination may cause different types of vasculitis, mPA and GCA, through the common mechanism in pathophysiology. This patient is also the first case of mPA and GCA proven by histological examination.     

Left ventricular apical and atrial appendage thrombus with hypertrophic cardiomyopathy in sinus rhythm: a case report

A 47-year-old female with a history of untreated hypertension and diabetes mellitus was referred because of a left ventricular echocardiographic mass with congestive heart failure. At the time of admission, she had already had a cardio-embolic stroke with loss of recent memory and slight paralysis of the right upper arm. It was difficult to distinguish between thrombus and tumor. However, her clinical condition required surgical resection as soon as possible. We performed cardiac CT to evaluate the coronary arteries and to scan the mass at the left ventricular apex. This CT evaluation revealed another mass at the left atrial appendage. Thus, these two masses were highly suggestive of thrombi. Subemergency surgical resection of the two masses and a part of the myocardium at the left ventricular apex was successfully performed. The pathological results showed that both the mass in the left ventricular apex and the mass in the left atrial appendage were thrombi, and the myocardial disarray confirmed the echocardiographic diagnosis as hypertrophic cardiomyopathy.     

Effect of maternal age and fertility treatment on the increase in multiple births in Japan: vital statistics, 1974-2009

Background

The present study used vital-statistics data to estimate the effect of maternal age and fertility treatment on the number and rate of multiple live births in Japan from 1974 through 2009.

Methods

Japanese vital statistics published by the Ministry of Health, Labour and Welfare from 1974 to 2009 were gathered and reanalyzed with regard to maternal age class and plurality of live births. The numbers of spontaneous and iatrogenic multiple births during 1977–2009 were estimated, with the assumption that spontaneous multiple-birth rates according to maternal age class would be constant and equal to those of baseline values, ie, the means between 1974 and 1976.

Results

During the 25-year period, multiple-birth rates according to maternal age class increased after the late 1980s. This tendency was obvious in women aged 35 to 39 years. The estimated numbers of iatrogenic multiple births remained nearly constant in women aged 20 to 24 years and greatly increased in women aged 30 to 34 and 35 to 39 years. The rate (per 1000 live births) of iatrogenic multiple births gradually increased from 0.7 (1977) to 1.3 (1986), then rapidly and markedly increased from 1.3 (1986) to 11.4 (2005), and finally decreased to 8.1 (2009). The estimated maximum percentage of iatrogenic multiple births was 50.0%, in 2004 and 2005.

Conclusions

The rapid increases in Japan in the number and rate of multiples born to women older than 30 years are likely due to iatrogenic rather than spontaneous multiple births.Key words: multiple-birth rate, spontaneous multiple births, iatrogenic multiple births, maternal age, fertility treatment     

Stimulation of 125I-3-iodo-α-methyl-l-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters

IntroductionTransport of the amino acid analog ¹²³I-3-iodo-α-methyl-l-tyrosine, which is used in clinical SPECT imaging, occurs mainly via l-type amino acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly expressed in actively proliferating tumors, we made a preliminary investigation of the effects of amino acid esters on enhancement of ¹²⁵I-3-iodo-α-methyl-l-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells.MethodsBecause the sequence of the CHO-K1 LAT1 gene is not available, we confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific inhibitors. l-Gly, l-Ser, l-Leu, l-Phe, l-Met, l-Tyr, d-Tyr, l-Val and l-Lys ethyl/methyl esters were tested in combination with IMT. Time-course studies over a 3-h period were conducted, and the concentration dependence of l-Tyr ethyl and methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a proof of de-esterification of l- and D-Tyr ethyl and methyl esters in the cells (by enzymatic attack or other cause), the concentration of l- and d-Tyr was analyzed by high-performance liquid chromatography of the esters in phosphate buffer (pH 7.4) and cell homogenates at 37°C or under ice-cold conditions.ResultsInhibition tests suggested that LAT1 is involved in IMT uptake by CHO-K1 cells. Co-administration of 1 mM of l-Tyr ethyl or methyl ester with IMT produced the greatest enhancement. The de-esterification reaction was stereo selective and temperature dependent in the homogenate. De-esterification kinetics were very fast in the homogenate and very slow in the phosphate buffer.ConclusionsThe l-Tyr ethyl or methyl esters were the most effective enhancers of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid exchange function of LAT1. This result suggests that de-esterification in the cells may be caused by enzymatic attack. We will use IMT and l-Tyr ethyl or methyl esters to examine LAT1 function in tumor cells or tissues in vivo.     

Brain surface motion imaging to predict adhesions between meningiomas and the brain surface

Introduction

“Brain surface motion imaging” (BSMI) is the subtraction of pulse-gated, 3D, heavily T2-weighted image of two different phases of cerebrospinal fluid (CSF) pulsation, which enables the assessment of the dynamics of brain surface pulsatile motion. The purpose of this study was to evaluate the feasibility of this imaging method for providing presurgical information about adhesions between meningiomas and the brain surface.

Methods

Eighteen cases with surgically resected meningioma in whom BSMI was presurgically obtained were studied. BSMI consisted of two sets of pulse-gated, 3D, heavily T2-weighted, fast spin echo scans. Images of the systolic phase and the diastolic phase were obtained, and subtraction was performed with 3D motion correction. We analyzed the presence of band-like texture surrounding the tumor and judged the degree of motion discrepancy as “total,” “partial,” or “none.” The correlation between BSMI and surgical findings was evaluated. For cases with partial adhesions, agreements in the locations of the adhesions were also evaluated.

Results

On presurgical BSMI, no motion discrepancy was seen in eight cases, partial in six cases, and total in four cases. These presurgical predictions about adhesions and surgical findings agreed in 13 cases (72.2%). The locations of adhesions agreed in five of six cases with partial adhesions.

Conclusion

In the current study, BSMI could predict brain and meningioma adhesions correctly in 72.2% of cases, and adhesion location could also be predicted. This imaging method appears to provide presurgical information about brain/meningioma adhesions.