Doxil--pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin (Doxil: PLD) is a liposome-encapsulated form of doxorubicin modified with polyethylene glycol that has been approved for the treatment of AIDS-related Kaposi's sarcoma. The characteristics of PLD are reduction of the severe side effects of cardiac toxicity and myelosuppression seen with doxorubicin, and a higher anti-tumor effect from the selective high maintenance of the drug concentration in the tumor tissue. This does not mean, however, that PLD should be used in the treatment of all patients with Kaposi's sarcoma; in some cases with skin lesions only and local distribution highly active antiretroviral therapy (HAART) alone is effective. While precise criteria for the use of PLD have not been determined, it is used in combination with HAART in patients with rapid progression, edema or strong pain, pulmonary complications, or extensive organ complications, or in cases when tumor progression is not slowed with HAART alone. Common side effects are myelosuppression and digestive symptoms, but when combined with HAART these complications do not become serious enough to lead to a discontinuation of treatment. The advantages of using PLD are less myelosuppression, less drug interaction, and the possibility of switching to outpatient administration. The level of treatment safety, tolerability, and treatment effectiveness makes it possible to investigate vigorous concomitant use with HAART, and expanded indications to other solid tumors may be expected.     

A comprehensive classification system of vestibular schwannomas.

Because traditional classifications of vestibular schwannomas (according to relative size) cannot comprehensively describe lesions that grow in different patterns after arising in regions as diverse as the cerebellopontine (CP) angle, the internal auditory canal, and the region lateral to the fundus of the internal auditory canal (labyrinth), we developed a new system to classify vestibular schwannomas, a system that describes the anatomical structures involved by the tumour, rather than size alone. The vestibular schwannoma is classified first by location and then by extent. Our system provides surgeons information helpful in choosing the surgical approach, in estimating the difficulty of tumour excision, and in determining whether hearing might be preserved. Our system also avoids confusion and misunderstanding in discussions of treatment results because it reflects the diverse biological characteristics of vestibular schwannomas.     

Chronic ischemic colonic lesion caused by phlebosclerosis with calcification

We report here two patients in both of whom ileus finally developed and chronic ischemic colonic lesion caused by phlebosclerosis with calcification was diagnosed. We believe that phlebosclerosis is an old-fashioned diagnostic term, but appropriate here because of the remarkable calcification of the sclerotic walls of the colic veins that seems to be one of the most important hallmarks of this previously unrecognized, "new" condition. Phlebosclerosis could be a novel type of ischemic colitis because of its unique clinical presentations, although the pathogenesis of this unusual venopathy remains unknown.     

Evaluation of pivot shift phenomenon while awake and under anaesthesia by different manoeuvres using triaxial accelerometer

Purpose

Evaluating pivot shift phenomenon is difficult due to its subjectivity, wide variation of testing manoeuvres, and difficulty in evaluating patients while awake. The purpose of this study was to evaluate the pivot shift phenomenon using a triaxial accelerometer by two different manoeuvres, the pivot shift test as representative of flexion manoeuvre and N test as a representative of extension manoeuvre, and in two different conditions, awake and under anaesthesia.

Methods

Twenty-nine patients with unilateral anterior cruciate ligament (ACL)-injured knee were included. Pivot shift test and N test were performed for both injured and uninjured legs while awake and under anaesthesia, with the acceleration measurements using a triaxial accelerometer (KiRA). The tests were also subjectively graded on a scale of 0–6 based on the modification of IKDC criteria.

Results

Under anaesthesia, acceleration of ACL-injured knees was greater than that of uninjured knees in both pivot shift test (P < 0.001) and N test (P < 0.001), whereas the acceleration value was greater in the N test. Furthermore, there were significant positive correlations between the acceleration and subjective grading in both tests, whereas the N test was more significant than the pivot shift test. On the other hand, there was no statistical significance in acceleration between ACL-injured and uninjured knees in either test while the patient was awake.

Conclusion

The triaxial accelerometer was useful to objectively detect and quantitatively evaluate the pivot shift phenomenon by both the pivot shift test and N test under anaesthesia. The acceleration of ACL-injured knees was greater than that of uninjured knees, and the acceleration was correlated with the subjective manual grading, especially in the N test. On the other hand, its use while the patient was awake was likely limited.

Levels of evidence

Diagnostic study of non-consecutive patients without a universally applied gold standard, Level III.

     

Blockade of astrocytic activation delays the occurrence of severe hypoxia-induced seizure and respiratory arrest in mice

Seizures are induced when subjects are exposed to severe hypoxia. It is followed by ventilatory fall-off and eventual respiratory arrest, which may underlie the pathophysiology of death in patients with epilepsy and severe respiratory disorders. However, the mechanisms of hypoxia-induced seizures have not been fully understood. Because astrocytes are involved in various neurological disorders, we aimed to investigate whether astrocytes are operational in seizure generation and respiratory arrest in a severe hypoxic condition. We examined the effects of astrocytic activation blockade on responses of EEG and ventilation to severe hypoxia. Adult mice were divided into two groups; in one group (n = 24) only vehicle was injected, and in the other group (n = 24) arundic acid, an inhibitory modulator of astrocytic activation, was administered before initiation of recording. After recording EEG and ventilation by whole body plethysmography in room air, the gas in the recording chamber was switched to 5% oxygen (nitrogen balanced) until a seizure and ventilatory depression occurred, followed by prompt switch back to room air. Severe hypoxia initially increased ventilation, followed by a seizure and ventilatory suppression in all mice examined. Fourteen mice without arundic acid showed respiratory arrest during loading of hypoxia. However, 22 mice pretreated with arundic acid did not suffer from respiratory arrest. Time from the onset of hypoxia to the occurrence of seizures was significantly longer in the group with arundic acid than that in the group without arundic acid. We suggest that blockade of astrocytic activation delays the occurrence of seizures and prevents respiratory arrest.     

Recent changes of the incidence of complete and partial mole in Chiba prefecture

AIMS: To study the changes of the incidence of complete mole (CM) and partial mole (PM) by 10-year age groups in Chiba Prefecture. METHODS: All women registered as CM and PMs in Chiba Prefecture during these 18 years were included in this study. The diagnosis of CM and PM was based on the macroscopic and/or microscopic findings. The annual numbers of pregnancy were obtained from the Division of Statistics in Chiba Prefecture Government. RESULTS: The incidence of CM at the upper and lower extremes of maternal age is higher than that of PM. The incidence of CM has decreased constantly at all maternal ages and significantly decreased in women of middle reproductive age (20-39 years old) since 1991, while that of PM has stayed constant during these 18 years. CONCLUSIONS: The incidence of CM and PM in Chiba Prefecture has become as low as that in Europe or the USA. These recent changes suggest that Japanese women may have lost the increased risk to ovulate a nuclear or inactive oocytes, or the differential diagnosis between CM and PM may be obscured with the macroscopic and/or microscopic findings.     

Increase of ATP level in human erythrocytes induced by S-adenosyl-L-methionine

The effect of S-adenosyl-L-methionine (SAM) on the ATP level, the morphology and the deformability of human erythrocytes was investigated and compared with that of adenosine. (i) Upon incubation with SAM, the ATP level increased considerably in fresh cells (in both young and old cells in similar extent) and in stored (partially ATP-depleted) cells. But the incubation with adenosine increased ATP level to a lesser extent. (ii) The incubation of stored cells with SAM hardly affected (or rather decreased) the IMP level, while that with adenosine remarkably increased IMP (and ITP). (iii) The morphology and the deformability of stored erythrocytes were well conserved in spite of the treatment with SAM, as compared with the treatment with adenosine. The echinocytic transformation was induced in old cells to some extent by SAM, while did not in young cells.     

Effect of cilostazol on vasomotor reactivity in patients with vasospastic angina pectoris

We examined the effects of cilostazol on impaired coronary arterial responses in patients with vasospastic angina (VSA). Thirty patients who were diagnosed with VSA based on an acetylcholine provocation test and 10 subjects with normal coronary arteries were enrolled. The patients were divided into the following 3 groups: no antiplatelet agent treatment group, aspirin treatment, or cilostazol treatment groups. Coronary flow reserve (CFR), coronary flow volume at maximum hyperemia, and epicardial coronary artery diameter after administration of N(G)-monomethyl-L-arginine (L-NMMA) were examined using a Doppler flow wire before and 6 months after the start of this study. CFR, coronary flow volume at maximum hyperemia, and diameter changes by L-NMMA were significantly increased in the cilostazol treatment group compared with the other 2 groups. In conclusion, cilostazol increased CFR and flow-dependent coronary dilation; these changes were attributable to nitric oxide. Cilostazol may improve coronary vascular endothelial dysfunction and coronary hemodynamics in patients with VSA.