CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

Histochemical studies on hyaluronic acid in the developing human retina

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and theStreptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks’ gestation to the neonatal stage.     

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Hypertonic saline alters electrical barrier of the airway epithelium.

OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND SETTING: We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. RESULTS: PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term.     

Effect of clot removal on cerebral vasospasm

The effect of clot removal on cerebral vasospasm was studied in 104 patients with aneurysmal subarachnoid hemorrhage (SAH). The series included patients who fulfilled all of the following criteria: operation was performed by Day 3 after the ictus; the patient's preoperative clinical grade was between Grades I and IV; there was no rebleeding; computerized tomography (CT) showed only SAH; and carotid angiograms were performed by Day 2 and repeated between Days 7 and 9. Both the degree of SAH on CT and angiographic vasospasm were graded from 0 to III. The relationship of the SAH grade in the basal frontal interhemispheric fissure (IHF) to the presence of vasospasm at the A2 segments of the anterior cerebral artery and the relationship of the SAH grade in the sylvian stems to the presence of vasospasm at the M1 segments of the middle cerebral artery were analyzed. Correlation of preoperative and postoperative SAH grades with the angiographic vasospasm grades, with the incidence of symptomatic vasospasm, and with the low-density area on CT could be found in the A2 and M1 territories. Decrease of cisternal blood measured by CT after the operation did not relate directly to the reduction of vasospasm. When the SAH was Grade II or III in the basal frontal IHF, the angiographic vasospasm grades at the A2 were significantly lower in patients with surgery via the interhemispheric approach than in those with surgery via the pterional approach. Symptomatic vasospasm occurred in two of the eight cases operated on by the interhemispheric approach compared with 11 of the 22 cases approached via the pterional route. In patients with a pterional approach, there was no significant difference in severity of vasospasm in the M1 territory between the side of approach and the opposite side. No consistent relationship could be found between the time interval from SAH to operation and the severity of vasospasm. While clot removal may ameliorate cerebral vasospasm, its effect per se does not seem to be significant.     

Moment analysis of drug disposition in kidney. II: Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney

Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p-aminohippurate, PAH) were investigated using the isolated erythrocyte-perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T cell) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vd drug). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vd drug, the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T cell of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush-border membranes. The present results coincide with the hypothetical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney.     

The non immunogenicity of CALLA in leukemic children

The sera from 55 children with acute lymphoblastic leukemia (ALL) treated with active immunotherapy were examined for the presence of antibodies against common ALL antigen (CALLA). A solid phase indirect radioimmunometric assay (IRA) was developed which enabled the detection of anti-CALLA antibody in patients' sera, utilizing the ability of affinity-purified CALLA to bind Ricinus communis agglutinin and anti-CALLA antibody simultaneously. Using IRA, anti-CALLA antibody activity could not be detected in a majority of patients. We concluded that the patients did not raise comparable antibodies against CALLA, indicating this antigen is not immunogenic for ALL patients.