Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study

OBJECTIVE: To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). PATIENTS AND METHODS: A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. RESULTS: In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. CONCLUSIONS: Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.     

Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid

We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition.     

Prenatal findings of holoprosencephaly

Holoprosencephaly (HPE) is a rare brain abnormality characterized by an incomplete cleavage of the primitive prosencephalon of forebrain during early embryogenesis. To determine the clinical characteristics and outcome of fetuses with HPE, we retrospectively analyzed nine patients who were prenatally diagnosed as fetal HPE by ultrasounds. The mean diagnostic weeks were 20 weeks of gestation. Two cases died within one day after birth. The chromosomal examinations were performed in seven cases (trisomy 18: n = 2; trisomy 13: n = 2; 45,XX,der(18)t(18;21)(p10;p10)mat: n = 1; normal karyotype: n = 2). In our HPE cases, most cases had serious facial anomalies and poor prognosis. Our data suggested that the early prenatal diagnosis of HPE allowed time for parental counseling and delivery planning.     

Annexin 5 messenger ribonucleic acid expression in pituitary gonadotropes is induced by gonadotropin-releasing hormone (GnRH) and modulates GnRH stimulation of gonadotropin release.

Our previous studies on annexin 5, a member of the annexin family of proteins, have shown its expression in the anterior pituitary gland, its preferential distribution in gonadotropes, and its increase after ovariectomy. In the present study, we examined (1) whether annexin 5 is synthesized in gonadotropes, (2) whether its expression is under the control of gonadotropin-releasing hormone (GnRH), and (3) the effect of annexin 5 on gonadotropin release. Large cells, also called castration cells, appeared in anterior pituitary tissue 3 weeks after ovariectomy. These cells have been confirmed to be hyperfunctioning gonadotropes and are easily discriminated from other pituitary cells without immunostaining. Using in situ hybridization with a digoxigenin-labeled ribonucleic acid probe, enhanced expression of annexin 5 messenger ribonucleic acid (mRNA) in these gonadotropes was clearly demonstrated. Northern blot analysis showed an increase in the level of annexin 5 mRNA expression 3 weeks after ovariectomy. It was lessened 3 h after the injection of Cetrorelix (GnRH antagonist, 10 microg i.v.). Administration of a GnRH analog [GnRHa; Des-Gly 10 (Pro9) GnRH ethylamide, 0.2 ml of 2.5 microg/ml saline ten times intraperitoneally at 30-min intervals] significantly increased pituitary annexin 5 mRNA. In primary cultures of anterior pituitary cells, recombinant rat annexin 5 stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a dose-dependent manner. Concomitant administration of annexin 5 (1 microg/ml) and GnRHa augmented the LH and FSH release induced by GnRHa. After a 1-hour incubation, cycloheximide (10 microg/ml) apparently inhibited the LH response to GnRHa, while annexin 5 (2 microg/ml) moderated this inhibition. Further, the antisense oligodeoxynucleotide to annexin 5 mRNA blunted the LH response to GnRHa. It is thus concluded that annexin 5 is synthesized in the gonadotropes under the effect of GnRH, and it is suggested that annexin 5 synthesis mediates at least partly GnRH receptor signaling to stimulate gonadotropin secretion.     

Successful laparoscopic extirpation of a large omental lipoblastoma in a child

Omental lipoblastoma is extremely rare among benign tumors. We herein report the case of a child who underwent laparoscopic extirpation of a large omental lipoblastoma. A 4‐year‐old girl was diagnosed with an intra‐abdominal solid tumor. Abdominal imaging revealed a fat density mass that was well encapsulated and measured 18 × 15 × 7.5 cm in size. Considering the MRI findings and movability of the tumor, we strongly suspected that the lesion was an omental lipoblastoma. We initially decided to perform laparoscopic exploration and, if possible, extirpation of the solid tumor sequentially. A total of five trocars were used, and the tumor was found to originate from the omentum. We successfully performed complete resection of the tumor laparoscopically. A histological examination revealed lipoblastoma. For large abdominal tumors in children, the laparoscopic approach is recommended as the first procedure when the tumor is preoperatively considered to be benign and resectable.     

Vascular-Resident CD169-Positive Monocytes and Macrophages Control Neutrophil Accumulation in the Kidney with Ischemia-Reperfusion Injury

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169⁺ monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169⁺ cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169⁺ monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169⁺ cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C^lo monocytes into CD169⁺ cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C^lo subset of CD169⁺ monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169⁺ monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.