Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

Relationship between Pathological Characteristics and Radiological Findings on Perfusion MR Imaging of Meningioma

Few studies have reviewed the roles of perfusion magnetic resonance (MR) imaging in the histopathological examination of meningiomas. We analyzed the relationships between radiological findings on perfusion MR imaging and pathological characteristics such as origin of the tumor, mitotic activity, pathological subtype, and perifocal edema formation. The subjects were 21 surgical cases of meningioma preoperatively evaluated by perfusion MR imaging. A region of interest (ROI) was set inside of the tumor, and perifocal edema of the same size, cerebral blood volume (CBV), and cerebral blood flow (CBF) on perfusion MR and diffusion-weighted (DW) imaging were analyzed. These radiological data were evaluated in comparison with histopathological characteristics. On perfusion MR imaging, the average ratio of CBV against the contralateral side was 6.43 (1.13–20.0) and that of CBF was 7.73 (1.34–11.3). There was no significant relationship with perfusion MR imaging data, tumor volume, or perifocal edema volume. However, the large peritumoral edema group often had a higher CBV and CBF than the non-large peritumoral edema group. The skull base group had a significantly higher CBV and lower signal intensity on DW images than the non-skull base group. Signal intensity on DW images was higher in grade II or III than in grade I. Perfusion MR imaging data revealed that the higher ratio of peritumoral edema against tumor size was associated with higher blood flow and blood volume under intratumoral circulatory conditions, and that skull base meningioma had a higher blood volume than non-skull base meningioma.     

Maximum Preservation of the Media in Carotid Endarterectomy

Carotid endarterectomy (CEA) is intended to remove atheromatous plaque by dissecting a plane between the intima and the media (circular medial fibers), but this may not be the optimal dissection plane. The present technique is based on identifying the plane that divides the media from the plaque, so preserving the media on the adventitia as much as possible. This plane is more difficult to find and follow than the easy-to-dissect plane usually located between the media and the adventitia, because the plaque invades the media and so the dividing plane is located within the media. In this prospective observational study, CEA was performed in 22 patients to histologically examine the excised plaques and small samples of the whole arterial wall, and evaluate the clinical outcomes. Plaque had invaded the luminal part of the media in the whole arterial wall sample of 80% of cases. Thin medial layers covering > 80% of the surface of the plaque were found in 16 of 22 plaques (73%). Some atheromatous component was sometimes left in the preserved media, rather than completely removed with the media. No morbidity or mortality had occurred by discharge. Only 1 small ipsilateral infarction (4.5%) and no restenosis of greater than 50% were detected during the mean follow-up period of 7 years. Since the plaque usually invades the media, the optimum dissection plane may be located within the media, dividing it into two layers. The presence of some remnant atheromatous components in the preserved media was not associated with surgical complications or restenosis.     

Adverse effects of anticholinergic activity on cognitive functions in Alzheimer's disease

Background:  Elderly patients with Alzheimer's disease (AD) take more medicines, other than those for anti-dementia agents, than healthy people and are sensitive to anticholinergic medications. There are only a few reports, however, on the relationship between cognitive function and anticholinergic activity in AD patients, which is caused by taking prescribed medication.
Methods:  We measured serum anticholinergic activity (SAA) in 76 AD patients referred to a Psychogeriatric Unit and separated them into SAA positive group ( n = 26, SAA (+) group) and SAA negative group ( n = 50, SAA (−) group). The difference in demographic data and cognitive functions were compared between the two groups.
Results and Conclusions:  The total scores of the Mini-Mental State Examination (MMSE), the score of MMSE domain of registration and recall were significantly lower ( P < 0.05) and the Functional Assessment Staging (FAST) score, the number of different kinds of prescribed psychotropic medications (the number of prescribed psychotropic medications) were significantly higher ( P < 0.05) in the SAA (+) group than in the SAA (−). These results suggest that a higher number of psychotropic medications prescribed leads to a tendency for SAA to be positive and that anticholinergic activity accelerates Alzheimer's pathology and decreases cognitive function, especially memory in AD patients. We should more prudently prescribe psychotropic medications to AD patients, because the prescribed psychotropic medications are one of the important causes of decline in cognitive function of AD patients by way of anticholinergic activity.     

The Protective Effect of 2-Mercapto-Ethane Sulfonate (MESNA) on Hemorrhagic Cystitis Induced by High-Dose Ifosfamide Treatment Tested by a Randomized Crossover Trial

High-dose ifosfamide (one or two courses of 6 g/m²) with orwithout mesna was administered to 13 patients with advancednon-small cell lung cancer. The protective effect of 2-mercapto-ethanesulfonate (mesna) against the urotoxic side effects inducedby ifosfamide was examined by a randomized crossover trial.A significant reduction in the incidence of hematuria was observedin the patients receiving mesna. Macroscopic hematuria was observedin only one patient who received treatment with mesna versusseven patients treated with ifosfamide alone. Other symptoms,such as frequency and dysuria, tended to be diminished in thepatients receiving mesna, although the difference was not statisticallysignificant. Our results suggest that mesna is effective inpreventing or diminishing ifosfamide-induced hemorrhagic cystitis.Concomitant use of mesna should allow the administration ofa high dose of ifosfamide although more extensive studies areneeded to define the optimal dose and schedule of administrationof mesna to prevent or attenuate the hemorrhagic cystitis.     

Very high doses of valsartan provide renoprotection independently of blood pressure in a type 2 diabetic nephropathy rat model

Aim:   Angiotensin II type 1 receptor blockers (ARB) retard the progression of hypertensive diabetic kidney disease. Clinical evidence suggests that the dose of ARB required to correct hypertension is suboptimal for renoprotection evaluated by proteinuria. No systematic, prospective study has yet evaluated separately the effect of increasing doses of ARB on blood pressure and proteinuria.
Methods:   Over a period of 8 weeks, the effect of seven constant doses of an ARB, valsartan (4–160 mg/kg per day), on blood pressure and proteinuria taken as a surrogate marker of nephropathy in a hypertensive, type 2 diabetic rat model, the spontaneously hypertensive/NIH-corpulent rat (SHR/NDmcr-cp), was assessed. In this spontaneously hypertensive rat strain, a genetic mutation in the leptin receptor gene is associated with hyperphagia leading to obesity with metabolic syndrome and eventually to nephropathy.
Results:   No additional blood pressure lowering was observed above 120 mg/kg per day of valsartan, suggesting that a dose of 80–120 mg/kg per day had a maximal effect. Nevertheless, higher doses of valsartan further reduced proteinuria in a dose-dependent fashion suggesting the absence of a maximal dose. Obesity, hyperglycaemia and hypercholesterolaemia were unaffected but hypertriglyceridaemia was partially corrected at various ARB doses.
Conclusion:   ARB improve renoprotection at doses above those required for a maximal effect on blood pressure. The mechanism of the renoprotection obtained at high doses of ARB is yet to be elucidated.     

Impact of COVID-19 on the Volume of Acute Stroke Admissions: A Nationwide Survey in Japan

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.     

Marked Reduction of Cerebral Vasospasm with Intrathecal Urokinase Infusion Therapy after Endovascular Coil Embolization of the Aneurysmal Subarachnoid Hemorrhage: A Case Series

Delayed cerebral vasospasms after subarachnoid hemorrhage (SAH) are a risk factor for poor prognosis after successful treatment of ruptured intracranial aneurysms. Different strategies to remove clots from the subarachnoid space and prevent vasospasms have different outcomes. Intrathecal urokinase infusion therapy combined with endovascular treatment (EVT) can reduce the incidence of symptomatic vasospasms. To analyze the relationship between symptomatic vasospasms and residual SAHs after urokinase infusion therapy, we retrospectively reviewed the records of 348 consecutive patients managed with EVT and intrathecal urokinase infusion therapy for aneurysmal SAH at our institution between 2010 and 2021. Among them, 163 patients met the study criteria and were classified into two groups according to the presence of residual SAH in the cisterns, Sylvian fissures, and frontal interhemispheric fissure. The incidence of symptomatic vasospasms and the clinical outcomes were assessed. In total, eight (5.0%) patients developed symptomatic vasospasms. Patients with symptomatic vasospasms had a significantly higher incidence of residual SAH in the Sylvian or frontal interhemispheric fissures than those without (P <.0001). No patient with SAHs resolved by urokinase infusion therapy developed symptomatic vasospasms. However, the two groups did not differ significantly in terms of modified Rankin scale scores at discharge. Treatment with intrathecal urokinase infusion after EVT for aneurysmal SAH can substantially reduce the risk of clinically evident vasospasms.     

Electronic-endoscopic Observation of ET-1 Induced Mucosal Ischemia and Preventive Effect of ETA Recepter Selective Antagonist,FR139317, in Rat Distal Colon

For investigation of the effects of Endothelin-1 (ET-1) on colonic mucosa, ET-1 (10–160 nmol/kg) was sprinkled on rat colonic mucosa under observation with a new electronic endoscopic system (TOSHIBA TRE-3000, Japan). A high dose of ET-1 induced complete obstruction of submucosal arterioles, but not venules, without affecting arterial blood pressure. The ET-1 -induced contraction of both vessel types was maintained for 50 min and was followed by intramucosal dot hemorrhages. In this experimental model, the effects of ET-1 on the mucosal microcirculation were further analyzed with a laser doppler blood flowmeter (LDF) during endoscopic observation. The maximum decrease in mucosal blood flow was to 20 % of the control value and this decrease was maintained for 20 min at a dose of 80 nmol/kg. An ETA receptor selective antagonist, FR139317 (800 nmol/kg), inhibited ET-1 -induced changes in endoscopic findings and LDF, shifting the concentration-response curve of LDF to the right. FR139317 is a potentially useful new therapy for inflammatory bowel diseases, conditions which have been reported to be associated with high local concentrations of ET-1. Our electronic-endoscopic system was demonstrated to be a useful basic research tool for studying gastrointestinal pathophysiology.     

Preliminary Phase II Study of Adriamycin (ADM) in Patients with Non-Small Cell Lung Cancer (NSCLC)

A phase II study of adriamycin (ADM) (60 mg/m² was performedin 22 patients with non-small cell lung carcinoma (NSCLC). Therewere no responders in the 19 evaluable patients (16 with adenocarcinoma,two with squamous cell carcinoma and one with large cell carcinoma).The major side effects were alopecia (89%), leukocytopenia (73%),thrombocytopenia (58%) and upper gastrointestinal symptoms. Although ADM at 60 mg/m² did not appear to have sufficient antitumoractivity against NSCLC in this study, it is necessary to evaluatefurther the efficacy of ADM against NSCLC with another treatmentschedule.