Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

A possible negative feedback control of excitatory transmission via prostaglandins in canine small intestine.

1 Contractile responses of canine intestinal circular and longitudinal muscles to field stimulation (20 Hz, 1 ms, 30 V/cm, for 5 s) were inhibited by treatment with atropine (0.1 microgram/ml), indicating that the response to field stimulation was mediated by acetylcholine (ACh). 2 Prostaglandins E1 (PGE1), PGE2 and PGF2 alpha inhibited the response of circular but not longitudinal muscle to field stimulation, although PGF2 alpha was less effective than PGE1 and E2. 3 PGE1 was much less active in inhibiting the response of circular muscle to ACh than to field stimulation, suggesting that prostaglandins might act predominantly at prejunctional sites to prevent the release of ACh. 4 Indomethacin (1 microgram/ml) potentiated the response of circular muscle but not longitudinal muscle to field stimulation. 5 Release of PGE-like compounds from circular muscle only, was increased by field stimulation at 20 Hz (total of 1000 pulses) and ACh (10 micrograms/ml), but not by a lower frequency (2 Hz, total of 2400 pulses) which produced only a slight contraction. This finding may indicate that prostaglandins were released predominantly from the muscle. 6 Prostaglandins may exert a negative feedback mechanism of excitatory transmission in circular muscle but not in longitudinal muscle of canine small intestine.     

A clinical evaluation of MK-0787/MK-0791 for long-term administration in urological infections

MK-0787 (Imipenem)/MK-0791 (Cilastatin sodium), a new compound of Thienamycin, was administered in treatment of 35 patients (36 cases) with chronic complicated UTI or for prevention of serious infections with much complicated factors. The patients were principally treated at a daily dose of 1 g for over 10 days. The efficacy rate of 26 patients who were evaluable in the early phase (4-7 days) was 88.5%, while it became up to 92.3% in the final phase judgment. As for clinical usefulness, the result was obtained to be as high as that of the clinical efficacy. In bacteriological study, 35 strains were clinically isolated including 7 strains of P. aeruginosa from UTI. All the strains disappeared with an eradication rate of 100% after treatment. Strains appearing after Imipenem/Cilastatin sodium treatment mainly consisted of fungi. Usefulness judgements tended to be greater in the final phase than in the early phase. As for side effects, vomiting was recorded in one case, in which the administration was discontinued. In laboratory findings there were 3 cases with elevated GPT, 2 cases with elevated GOT, one case with elevated gamma-GTP, one with thrombocytopenia, and one with eosinophilia each, but these abnormal values were slight and transient. In summary our clinical study showed that Imipenem/Cilastatin sodium was a very effective antibiotic in treatment on moderate or serious UTI or preventive use for infections in compromised hosts. Considering the features of this agent, it might be more effective and useful for clinical use in treatment on polymicrobial infections including stubborn organisms than any other antimicrobial compounds. Furthermore, it was safe and well tolerable in a long term treatment.     

Sequence-dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) Monohydrate

We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.     

Correlation of fetal posture and congenital dislocation of the hip

A statistical study was carried out on the incidence of CDH associated with mechanical factors in the uterus, including congenital genu recurvatum. There were 72 cases of CDH among 6559 infants (1.1 per cent). The incidence of CDH was 0.7 per cent in cephalic presentation, 2 per cent in footling presentation and 20 per cent in single-breech presentation. In another series, CDH was found in six of seven infants with congenital genu recurvatum. These findings suggest that a fetal posture with the hip flexed and the knee extended predisposes to the development of CDH.     

Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A.

In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.