Pulmonary alveolar proteinosis as a terminal complication in myelodysplastic syndromes: a report of four cases detected on autopsy

Secondary pulmonary alveolar proteinosis (PAP) is one of the complications of hematologic malignancy and immunosuppressive diseases. We encountered four cases of myelodysplastic syndrome (MDS) associated with PAP detected on autopsy. They consisted of two refractory anemia (RA) and two patients with refractory anemia with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but all of them developed leukemic phase and were resistant to chemotherapy at the time of pulmonary episodes. Of the four MDS patients, two also had pulmonary aspergillosis. Previously, 69 patients with PAP associated with hematologic disorders have been reported, but there have been only seven cases with MDS, including our four patients. Of the 69 reported cases of PAP in hematologic malignancies, 24/63 (38%) informative patients with infection had fungal infections of the lung; 2/7 (29%) MDS cases had fungal infection. We should, therefore, pay careful attention to this possibility in cases of MDS with lung complications, including PAP, especially in patients in the leukemic phase of MDS.     

Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts

The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.     

Isoflurane ameliorates the posthypoxic deoxygenation of the rat brain--the role of cell adhesion molecules of polymorphonuclear leukocytes

One of the serious problems that occurs after cardiopulmonary resuscitation is brain posthypoxic/ischemic deoxygenation. However, there has been no report concerning the effect of isoflurane (ISO) on the brain oxygenation during hypoxia-reoxygenation in relation to cell adhesion molecules (CD11b) in polymorphonuclear leukocyte. Rats were anesthetized with a low concentration of ISO (0.5 MAC: low ISO) or high concentration of ISO (1.5 MAC: high ISO) and brain oxygenation was detected by near infrared spectroscopy during 10-min hypoxia (5% O(2)) and a subsequent 120-min reoxygenation period. Hypoxia induced a decrease in oxyhemoglobin (HbO(2)) and an increase in deoxyhemoglobin (Hb). Reoxygenation induced a significant decrease in total hemoglobin (tHb) and HbO(2) with low ISO, but not with high ISO. The changes in Hb were minimal during reoxygenation in both groups. CD11b increased during reoxygenation with low ISO anesthetization, but not with high ISO. A significant negative correlation was observed between CD11b and two of the measured oxyparameters, HbO(2) and tHb, during reoxygenation at low ISO, but not at high ISO. These findings suggest that brain deoxygenation during hypoxia-reoxygenation is partly related to the expression of CD11b. We conclude that ISO modifies the brain circulation at least in part through attenuating the expression of CD11b during hypoxia-reoxygenation.     

Improvement in jaw motion following treatment of unilateral crossbite in a child with primary dentition: a case report

This case report examines jaw motion during both habitual opening-closing and gum chewing in a young (3 years, 10 months) patient with unilateral crossbite at the primary dentition stage. Jaw motion was measured three times: 1. before treatment; 2. after active treatment; and 3. after retention. The abnormal habitual open-close pathway seen prior to treatment was improved after retention. Prior to treatment, movement of the affected-side condyle preceded movement of the non-affected-side condyle during opening. After retention, the movement of the condyles was better coordinated. The chopping type chewing pattern, with less lateral movement, before treatment changed to a more grinding type pattern on the affected side after activation. This study suggests that the prescribed treatment effectively improved both the patient's morphology and function. However, neither the open-close pathways nor the chewing patterns were completely normal after retention. The results in this case suggest that early treatment of functional unilateral crossbite can be effective.     

Type II pneumocytes in the evaluation of drug antimycobacterial activity

In order to combat the worldwide increase in the prevalence of multi-drug resistant tuberculosis and Mycobacterium avium complex infections, a number of new antimycobacterial drugs has been synthesised and developed. There is great promise for drugs designed by new strategies, especially those based on the information on mycobacterial genome sequences and a host-parasite relationship. Moreover, the development of new protocols for chemotherapy of intractable mycobacterioses is also needed. For this purpose, better in vitro drug activity assay models that enable prediction of therapeutic activity, particularly those predicting the in vivo sterilising activity, are urgently needed, since the ordinary in vitro methods are inefficient indicators of clinical efficacy. In this context, the in vitro models using Type II pneumocytes, which play an important role in the establishment of mycobacterial pulmonary infections as a portal of mycobacterial organisms to the lungs, are considerably useful, especially in predicting the in vivo activity of certain drugs against Mycobacterium avium complex infection.     

Present status and future prospects of chemotherapeutics for intractable infections due to Mycobacterium avium complex

Mycobacterium avium-intracellulare complex (MAC) infections are frequently encountered in immunocompromised hosts, especially AIDS patients, although nodular-bronchiectasis type MAC infections without predisposing conditions are steadily increasing, particularly in Japan. Clinical control of MAC infection is difficult, since it responds poorly to available antimycobacterial regimens because of the intrinsic resistance of MAC organisms to common antituberculosis drugs, although some antimycobacterial drugs, such as macrolides (clarithromycin, azithromycin), ethambutol, clofazimine and rifamycins (especially rifabutin), are fairly or modestly effective in controlling AIDS-associated MAC bacteremia. In addition, treatment of pulmonary MAC infections is also difficult, even with available antimycobacterial multi-drug therapies. The insufficient efficacy of the majority of ordinary antimycobacterial drugs in treating MAC diseases is principally due to the low susceptibility of MAC to the majority of ordinary antimycobacterial drugs, the extremely wide range of susceptibilities of MAC isolates to most antimicrobial drugs, and the fact that polyclonal MAC infections are occasionally seen in AIDS patients. Therefore, the development of new antimicrobials and administration protocols that are safe and potently effective against MAC infections is urgently needed. However, despite the gradual but steady increase in the incidence of MAC infections, and thereby the urgent call for new drug development, new drugs that are truly useful for the treatment of refractory MAC diseases continue to elude us. In this review article, the following topics will be described: (1) the present status of the existing anti-MAC drugs, with special reference to the recent findings of the in vitro and in vivo anti-MAC activities of macrolides and other moderately useful drugs, such as new rifamycins, clofazimine and some fluoroquinolones, and (2) the present status and future prospects of the development of new promising antimicrobials with anti-MAC activity.