The clinical significance of exercise-induced ST segment changes in patients with previous inferior myocardial infarction

To investigate the clinical significance of exercise-induced ST changes, we performed exercise body surface mapping (87 leads) in 52 patients (one-vessel disease [1 VD] n = 12, multivessel disease [MVD] n = 40) with previous inferior myocardial infarction (MI). ST isointegral maps were constructed and the locations of ST changes were compared with the findings of exercise thallium-201 (TI-201) myocardial scanning. Exercise-induced ST elevation was observed in 14 patients (27%) on the lower chest and on the back, corresponding to the infarcted area. Exercise-induced ST depression was observed more frequently in the MVD group (n = 30, 75%) than in the 1VD group (n = 2, 17%). Seventeen (77%) of 22 patients with ST depression had thallium-201 redistribution. There was a significant association between ST depression and TI-201 redistribution (chi2 = 13.1, p less than 0.001), but no association between ST depression and ST elevation. The body surface distribution of ST depression was shifted upward and rightward compared with its appearance in angina pectoris without MI. These findings suggest that exercise-induced ST depression reflects myocardial ischemia in patients with previous inferior MI.     

Unexpected intraoperative obstruction of frozen elephant trunk in patients who underwent total arch replacement

Currently, total arch replacement (TAR) using frozen elephant trunk (FET) technique is gaining popularity for various thoracic aortic pathologies. FROZENIX is the first commercialized open stent‐graft (OSG) in Japan, and it is a useful alternative to previously self‐made OSG. FROZENIX is easy to deploy compared with formerly launched OSGs. However, some challenges have been identified with FROZENIX. Herein, we present the cases of two patients in whom we encountered serious unexpected kinking of FROZENIX during TAR performed using FET, which was related to its structural property. The clinical course and the bailout are described.     

A bronchial glomus tumor surgically treated with segmental resection

Extracutaneous glomus tumors are unusual and their occurrence in bronchus has been recognized with rarity. We present the clinical and pathological features of a case with bronchial glomus tumor. A 67-year-old man was admitted with a symptom of cough, and his chest CT scan and fiberoptic bronchoscopy demonstrated a localized polypoid tumor in the right superior bronchial trunk. Histology of the biopsy specimen by bronchoscopy was demonstrated as a typical carcinoid tumor. The tumor was surgically resected by a segmental resection of the right superior bronchial trunk and end-to-end anastomosis was followed to reconstruct the airway tract through a standard right side thoracotomy approach. The pathological and immunohistochemical findings resulted in the diagnosis of the tumor as a bronchial glomus tumor.     

Aortic remodelling effect of the frozen elephant trunk technique on Stanford type A acute aortic dissection

Total arch replacement using the frozen elephant trunk procedure is performed for true lumen expansion of the descending aorta in patients with type A acute aortic dissection. However, the remodelling effect of the frozen elephant trunk on the dissected descending aorta is unclear. We aimed to evaluate the effect of the frozen elephant trunk on postoperative descending aortic remodelling after surgery. Between December 2012 and January 2020, we retrospectively investigated 24 patients who underwent total arch replacement using the frozen elephant trunk for type A acute aortic dissection. Remodelling of the descending aorta was evaluated using computed tomography. The aortic remodelling effect, based on aortic true lumen ratio, was determined for (i) DeBakey type (type I versus type III retrograde); (ii) thoracic endovascular aneurysm repair reintervention status (reintervention versus no reintervention); and (iii) stent length of the frozen elephant trunk (60 vs 90 mm). Postoperative true lumen ratio significantly increased in the type I dissection group. The true lumen ratio in the no-reintervention group, which had many patients with the type I dissection, significantly increased after the frozen elephant trunk. Aortic remodelling due to the frozen elephant trunk can be expected after type I acute aortic dissections.     

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.

     

Significance of mesangial expression of alpha-smooth muscle actin in the progression of IgA nephropathy.

To determine whether phenotypic modulation of mesangial and interstitial cells correlated with the long-term prognosis of IgA nephropathy (IgAN), we analyzed retrospectively 27 patients with IgAN whose creatinine clearance at the time of renal biopsy was normal. The patients were subdivided into two groups according to the course of renal function during follow-up. Thirteen patients maintained normal renal function for more than 15 years (stable group), and 14 progressed to end-stage renal disease (ESRD group). The score of mesangial cell cellularity in the ESRD group was significantly higher than in the stable group. Immunohistochemistry localized alpha-smooth muscle actin (alpha-SMA) in renal mesangial cells of approximately half these patients. Macrophages localized predominantly in the mesangial area in patients with mesangial expression of alpha-SMA, which was associated with the expression of macrophage-colony-stimulating factor. Noteworthily, the score of mesangial alpha-SMA expression and the incidence of patients with mesangial expression of alpha-SMA at the time of renal biopsy were markedly higher in the ESRD group than in the stable group. However, there was no significant difference in both the score of interstitial alpha-SMA expression and the incidence of patients with interstitial expression of alpha-SMA between these two groups. These results suggest that macrophages recruited into the mesangium may induce phenotypic modulation of mesangial cells and that mesangial alpha-SMA expression predicts a progressive decline in renal function in patients with IgAN.     

Clinical characteristics of renal damage in patients with accidental hypothermia]

We have investigated the clinical characteristics of renal damage and associated complications of 79 patients with accidental hypothermia whom we encountered over the last 5 years. All patients were male, with an average age of 58.9 +/- 9.2 years. Most of these patients were homeless. Body temperature on admission was 29.3 +/- 3.0 degrees C. The most common clinical manifestations on admission were consciousness disturbance and severe hypotension. Complications, including increase in serum transaminase, alcoholism, pneumonia, liver cirrhosis, sepsis, diabetes mellitus, hypoglycemia, acidosis, and an increased level of serum CPK and amylase were found frequently on admission. Death within 48 hours after admission occurred in 23 cases (the death rate; 23/79 = 29%). Renal damage was found in 36 cases (36/79 = 46%), consisting of acute renal failure (ARF) in 27, and acute on chronic in 6. Urinary diagnostic indices suggested that the etiological factor for ARF was pre-renal, which responded well to passive rewarming and an appropriate fluid replacement therapy, resulting in full recovery in most of the cases (the recovery rate; 25/27 = 93%). Among patients with renal damage, there were no cases requiring dialysis. The present data suggest that accidental hypothermia is a fatal condition with an extremely high death rate. It also is associated with multiple complications including ARF. The main cause for ARF is pre-renal, possibly caused by cold diuresis or dehydration superimposed on the underlying diseases such as alcoholism, diabetes mellitus, liver cirrhosis. Such complications, independent of renal damage, determine the patient's prognosis.     

Comparison of alternate-day versus consecutive-day treatment with S-1: assessment of tumor growth inhibition and toxicity reduction in gastric cancer cell lines in vitro and in vivo

Background  The toxic effects of S-1 can lead to discontinuation of treatment. Strategies for reducing toxicity without compromising therapeutic effectiveness are required. Methods  We used the human gastric cancer cell lines MKN28 and MKN45 to examine such strategies in vitro. The cell lines were treated with three different regimens, given on alternate days (alternate-day) or on consecutive days (consecutive-day). On consecutive days, treatment A provided the same total dose as the alternate-day treatment, and treatment B was given for the same number of days as the alternate-day treatment. A fourth group served as control. In vitro, the relative inhibition (RI) of tumor growth by 5-fluorouracil was calculated using the 2-(2-methyl-4-nitrophenyl)-3-(4-nitrophyl)-5-2, 4-disulfophenyl)-2H-tetrazolium (WST-8) method. We also carried out an in vivo experiment in which tumor-bearing nude mice (BALBc/nu-nu) were used to examine the antitumor activity of S-1. Leukocyte counts and gastrointestinal mucosal injury were compared in mice that received alternate-day and consecutive-day treatments. Results  In vitro, for MKN28, the RI was 22.9% for alternate-day, 34.1% for consecutive-day A, and 37.7% for consecutive-day B treatments. For MKN45, the RI was 51.1% for alternate-day, 52.2% for consecutive-day A, and 50.5% for consecutive-day B treatments. In vivo, for MKN28, the treated groups showed higher inhibition than the control, and inhibition of tumor growth was higher with alternate-day than with consecutive-day treatment. The RI was significantly higher with alternate-day (49.3%) than with consecutive-day treatment (16.2%; P < 0.05). For MKN45, the RI was greater than 50% in both treated groups. With consecutive-day treatment, 5 of the 14 mice used died during treatment. Leukocyte counts were lower in the mice with consecutive-day than with alternate-day treatment, or control. Atrophic changes and inflammatory cell infiltration of the small intestinal mucosa were severe after consecutive-day, but minimal after alternate-day treatment. Conclusion  Experimentally, alternate-day treatment with S-1 is equivalent to consecutive-day treatment in terms of RI of tumor growth, with lower toxicity.     

Principles of Total Care for Children with Leukemia —Psychosocial Interventions —

Today about 70% of children with leukemia are cured by intensive chemotherapy. Therefore how to deal with the children and their families before, during, and after the treatment has become a major concern for caregivers. And it is a fact that there are still a few patients who relapse and are destined to die. We are now taking care of two groups of patients. One group is truly cured and one group is dying. We have been trying to establish a good total care system that fits our society. We have formed medical teams which consist of doctors, nurses, and care workers. From our experience, we think the most important principle for the caregivers is frankness. Sometimes this is very difficult. Other important points of total care, especially from psychosocial aspects, are mentioned.