Pharmacokinetic evaluation of high pulmonary disposition of clarithromycin after systemic administration.

1. The distribution characteristics of clarithromycin to the lung were investigated in vivo and in isolated lung perfusion experiments. The in-vivo integration plot analysis showed that the pulmonary uptake and extracellular distribution in the lung were significantly higher for clarithromycin than for erythromycin. 2. In the rat lung single-pass perfusion study, the pulmonary extraction ratio (E(ss)) of clarithromycin at steady-state was significantly higher than that of erythromycin, and the E(ss) of clarithromycin tended to decrease as the inflow concentration increased, suggesting the involvement of carrier-mediated transport in the pulmonary disposition of clarithromycin. 3. The outflow patterns of clarithromycin or erythromycin at various inflow concentrations were simultaneously analysed based on a pharmacokinetic model, which consists of the non-specific binding site, the specific binding site and the subsequent uptake process. The parameters obtained suggested that clarithromycin would have the higher affinity and higher capacity for the specific binding site, and the higher equilibrium constant for the non-specific binding site than erythromycin. 4. The simulation study using those parameters demonstrated that clarithromycin could be bound to the specific binding site and subsequently taken up more extensively than erythromycin. 5. A multiple-indicator dilution study also indicated that clarithromycin was more readily associated and extracted with the lung than with erythromycin. In the inhibition study, it was suggested that the pulmonary uptake of clarithromycin could be ascribed not only to the non-specific binding depending on its lipophilic nature, but also in part to some specialized mechanisms such as organic cation transporters.

A huge frontal meningioma associated with intraoperative massive bleeding and severe brain swelling--case report.

A 58 year old female presented with progressive memory disturbance and personality change. Magnetic resonance (MR) imaging disclosed a huge mass lesion accompanied by prominent oedema in the right frontal lobe. Cerebral angiogram demonstrated a vascular-rich tumour and a major drainer through diploic vein. A right frontotemporal craniotomy was performed. We encountered massive bleeding from diploic vein and dura mater immediately at the craniotomy. We were also faced with severe brain swelling at the dural incision. The tumour was solid, highly vascularised, and fairly well demarcated. We performed total removal of the tumour as quickly as possible in order to reduce the intracranial hypertension and avoid the impending brain herniation. The patient had an uneventful recovery and was asymptomatic at 10 months follow-up.

The processing of global and local visual information in Alzheimer's disease.

We examined the quantitative and qualitative difference of the pattern with visuo-cognitive processing impairment in patients with early onset AD (EOAD) and late onset AD (LOAD). We use a visual attention task introduced by Navon (1977) to examine the function to integrate local visual stimuli into global image. Although the ability to identify solid digits ether of large and small size presented at the same exposure duration, EOAD performance was poor in the global perception especially at the short duration (20~msec). We provide evidence that this dysfunction is attribute to the AD pathology specific to early onset type.

A new metal-binding site in photosynthetic bacterial reaction centers that modulates QA to QB electron transfer.

Isolated reaction centers (RCs) from Rhodobacter sphaeroides were found to bind Zn(II) stoichiometrically and reversibly in addition to the 1 equiv of non-heme Fe(II). Metal and EPR analyses confirm that Zn(II) is ligated to a binding site that is distinct from the Fe site. When Zn(II) is bound to this site, electron transfer between the quinones QA and QB (QA-QB --> QAQB-) is slowed and the room-temperature kinetics become distributed across the microsecond to millisecond time domain. This effect of metal binding on the kinetics is similar to the more global effect of cooling RCs to 2 degreesC in the absence of Zn(II). This suggests that Zn(II) binding alters localized protein motions that are necessary for rapid QA-QB --> QAQB- electron transfer. Inspection of the RC crystal structure suggests a cluster of histidine ligands located beneath the QB binding pocket as a potential binding site.

Remote-control vascular occluder: technical note.

We have designed a new remote-control vascular occluder for the temporary control of arterial blood flow. It is a modification of the biopsy forceps used in stereotactic surgery. The arm of the occluder is flexible and can be set so that it does not disturb the surgeon's view. The occluder is positioned with the blades open on the vessel to be occluded. This device, which is held with a self-retaining retractor connected to the head frame, enables an immediate on-off remote control of arterial occlusion by closing and releasing the blades with a closing button and releasing lever, respectively. Partial closure of the blades is also feasible. The device can be set in a narrow operating field, when proximal control of a parent artery is necessary at its segment distant from the exposed operating field. It can be used in a variety of vascular cases, including giant aneurysms and large arteriovenous malformations.

[Generalized choreic movement associated with subarachnoid hemorrhage].

A case of generalized choreic movement associated with subarachnoid hemorrhage is reported. A 71 year-old hypertensive woman suddenly developed severe headache 14 days before admission. Consciousness disturbance and involuntary movement involving the face and upper extremities appeared about 8 days after onset. The involuntary motion was diagnosed as generalized choreic movement. CT scans showed subarachnoid hemorrhage with ventricular dilatation and periventricular lucency involving bilateral caudate nuclei. On admission the patient was stuporous with Hunt & Kosnik Grade 4. She showed involuntary choreic movement in both arms, trunk and face; hemiparenis and hyperreflexia were absent. An angiography revealed a right internal carotid-anterior choroidal artery aneurysm with vasospasm. After clipping the aneurysm in the following day, the consciousness disturbance and choreic movement gradually improved. By eight days after operation, the choreic movement completely disappeared. An MRI showed lacunar infarcts in the bilateral basal ganglia, predominantly in the caudate nuclei. In our case, the choreic movement is supposed to have been caused by impaired circulation in the bilateral corpora striata due to vasospasm and hydrocephalus after subarachnoid hemorrhage, in addition to the preexisting lacunar infarcts in the basal ganglia. This is claimed to be the first reported case of generalized choreic movement in associated with subarachnoid hemorrhage, which improved after surgery.

[Left unilateral apraxia].

A 32-year-old right-handed man suffered a traffic accident with head injury, resulting in loss of spontaneity, right hemiparesis, severe aphasia, and unilateral apraxia, which was noticed on his non-paralyzed left hand. An MRI scan conducted 11 months after onset revealed a large lesion in the left frontal lobe, a small lesion in the right frontal lobe and a striking thinning of the trunk of the corpus callosum with remarkable dilatation of the lateral ventricles. An IMP-SPECT scan, performed 1 year after onset, showed a diffuse hypoperfusion extending to the left temporo-parietal area further than the MRI verified abnormal density areas. The patient's praxic abilities were precisely evaluated 1 year after onset. The performance on the object use task was characterized by content errors. For example, when using a match with his left hand, he always treated with it like a cigarette. The right hand performance of this task was clumsy due to his right hemiparesis but successful. The performance on his left hand did not improved even when the patient was given visual examples. The term "ideational apraxia" proposed by Liepmann, which was characterized by content errors, implies a conceptual deficit. Morlaas defined ideational apraxia as a agnosia of usage. Ideational apraxia has been so far investigated mainly on patients with these difficulties in both hands. On the other hand, left unilateral apraxia has been explained by callosal disconnection. Liepmann and Maas thought that a lesion of the corpus callosum would prevent the space-time engrams in the left hemisphere from reaching the right sensorimotor area necessary to carry out the skilled act with the left hand, thereby inducing apraxia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bilateral crossed visuomotor ataxia--a case report].

We observed a 55 y.o. right-handed woman, who was suspected of splenium tumor (glioblastoma?) by CT scan and presented bilateral crossed visuomotor ataxia proposed by Rondot et al. Left unilateral apraxia and agraphia were not found, but left unilateral hemialexia was evident by tachistoscopic examinations. In regard to bilateral crossed visuomotor ataxia, we suggested that at least there might be three possible hypotheses about its realization mechanism. (1) Callosal lesion might disconnect heterotopical fibers which runs from one occipital lobe to another frontal lobe. (2) Integrated information of visual and proprioceptive inputs in the parieto-occipital regions could not be transferred mutually to other side of the brain. (3) Functional dissociation between visual perception of "moving" and that of "position" might be the cause of this symptom. Former could be transferred via subcallosal pathway, but latter not transferred due to the callosal lesion. Hypothesis (1) could not explain, at least, "positive aspects" of this symptom, and which hypothesis is most probable might not be decided at present, because anatomical evidence and patho-plastic mechanism are not yet clarified.

[Agraphia of the left hand--its characteristics and mechanism of development].

We observed 62 y.o. right-handed woman, whose truncus of corps callosum was damaged by infarction of left anterior cerebral artery, that was verified by coronal CT scan finding. She was apraxic and agraphic only with left hand. We examined the characteristics of her unilateral left agraphia from the point of quantitative and qualitative views. These analysis seemed to reveal three main characteristics of unilateral left agraphia of this patient. These were as follows; 1) productive, 2) neographic and 3) iterative. Another important feature of this patient was the mute state during her left-hand writing. Her left agraphia could not explained by apraxic factor, because her copying capacity was remarkably preserved in comparison with her dictation or written naming ability. Furthermore, this agraphia was not aphasic because her right-hand writing was almost intact. We agreed with Yamadori who insisted that this type of agraphia was neither apraxic nor aphasic, but the particular third agraphia which was named as "disconnection agraphia". We considered that the mute state during her left-hand writing might some kind of transient aphasia, which may reflect the functional disturbance of left hemisphere, and the reduced energy in the left hemisphere could increase the activity of right hemisphere. Partial interhemispheric disconnection might induce transient "linguistic anosognosia" in this patient. We believe that these transient hyperactivity and transient linguistic anosognosia could generate above mentioned characteristics of her left agraphia; productive, neographic and iterative.

[Broca's area and Broca's aphasia: based on the observations of two cases with the lesions involving Broca's area].

Recently, the relation between Broca's area and Broca's aphasia has come into notice again. We investigated two right-handed patients without Broca's aphasia in spite of the presence of lesions involving Broca's area after hemorrhagic infarction. In addition, the clinical findings, the clinical courses and the sites of lesions of two cases were quite similar as follows. They showed no motor deficits and no other abnormal neurological findings from the beginning of the strokes. From the near muteness in the initial stage, speech began to improve gradually. And then, they demonstrated so called transcortical motor aphasia. Namely, repetition and reading aloud were excellent and articulations were normal without phonetic disintegration and dysprosody in contrast to the sparse and limited spontaneous speech. Comprehension was well preserved. Anomia was present and the ability to generate word lists was so poor that, for instance, only two animal names were listed in one minute. Mild to moderate agraphia was present. Agrammatism and buccofacial apraxia were not associated. Afterwards, the two patients showed rapid amelioration. About one month later after the stroke, only a slight difficulty in word finding and mild agraphia remained. In both cases, the lesions confined predominantly to the cortical and subcortical areas in the left posterior part of both the third and the second frontal gyri were confirmed by computerized tomography. According to the evidence from our two cases and to the literature, it may be concluded that the lesion restricted to the posterior part of the third and second frontal gyri in the dominant hemisphere produces a subtype of transcortical motor aphasia and that the lesion restricted to the posterior part of the third frontal gyrus (Broca's area) does not lead to phonetic disintegration.

[Heterogeneity of bucco-facial apraxia]. / A propos de l'hétérogénéité de l'apraxie bucco-faciale.

The authors have studied the bucco-facial apraxia (BFA) in 20 aphasic patients, examining 10 isolated oral gesture (IOG) and 10 combined oral gesture (COG). The heterogeneity of the BFA is indicated by the qualitative analysis of the types of errors in COG in relation to IOG. It is probably that the BFA due to the posterior lesions might base on the motor programming disorders of oral gestures, and that the BFA due to the anterior lesions on the motor realization disorders of oral gestures. It remains unsolved whether there is a continuity or some varieties between two types of BFA.