Vitamin B12 treatment for delayed sleep phase syndrome: A multi-center double-blind study

Abstract  The active form of vitamin B₁₂ (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B₁₂ has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13–55 years (26.8 ± 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.     

Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy

Abstract. Although granulocyte-colony stimulating factor (G-CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G-CSF in healthy women is still obscure due to the low sensitivity (30 pg mL^-1) of the usual enzyme immunoassay. With the development of a highly sensitive (l.0 pg mL^-1) chemiluminescent immunoassay by Kiriyama et al ., we have clarified the changes of serum G-CSF levels in healthy women during the menstrual cycle and pregnancy. The G-CSF concentration showed a peak value of 27.3± 2.5 pg mL^-1 (mean±SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases ( P < 0.0001, unpaired t -test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy ( P < 0.0001, unpaired t -test). These results suggest that G-CSF plays an important role in ovulation and the maintenance of pregnancy.     

Hypertensive crisis after discontinuation of an angiotensin-converting enzyme inhibitor in a patient with renal dysfunction

SUMMARY: A 54-year-old woman with hypertension treated for 2 years with enalapril, 10 mg daily, was admitted to hospital because of progressively worsening renal function. There was no evidence of scleroderma, except for the presence of anticentromere antibodies. to prevent hyperkalaemia and further deterioration of renal function, enalapril was abruptly withdrawn and replaced with a calcium antagonist on the second hospital day, but hypertensive crisis developed. Renal failure requiring haemodialysis developed 2 weeks after admission. Findings of a renal biopsy were consistent with scleroderma kidney. Scleroderma is difficult to diagnose in the absence of cutaneous symptoms. Therefore, angiotensin-converting enzyme inhibitors should only be discontinued with care in patients with renal dysfunction if there is the possibility of scleroderma without skin changes.     

Disposition of Polaprezinc (Zinc l-Carnosine Complex) in Rat Gastrointestinal Tract and Effect of Cimetidine on its Adhesion to Gastric Tissues

The disposition of polaprezinc in the rat gastrointestinal tract was studied by a double tracer method using [¹⁴C]- and [⁶⁵Zn]polaprezinc. At 0·5 h after oral administration of [¹⁴C]-, [⁶⁵Zn]polaprezinc to rats, the ¹⁴C-radioactivity in the gastric contents was comparable with the ⁶⁵Zn-radioactivity. However, a significant difference was observed in the time course of changes in gastric contents between ¹⁴C- and ⁶⁵Zn-radioactivity over 1 h after administration, indicating that polaprezinc existed in complex form at 0·5 h after administration and was dissociated to l -carnosine and zinc in the gastrointestinal tract as a function of time. The adhesion of zinc to stomach mucosa after oral administration of polaprezinc to rats was significantly increased by treatment with cimetidine. These results suggest that the adhesion of zinc to gastric tissues is increased by inhibiting the dissociation of polaprezinc, and that H₂-receptor antagonists, such as cimetidine, may increase anti-ulcer effects of polaprezinc.     

Characteristics of behavioral and psychological symptoms in the oldest patients with Alzheimer's disease

Background: Advancing age increases the risk of developing dementia. Recent studies have clarified characteristic cognitive changes in very old patients with dementia. Although non‐cognitive symptoms are frequent in dementia, relatively little attention has been paid to the nature of behavioral and psychological symptoms of dementia (BPSD). Methods: A retrospective review of a database was performed to compare 27 very old patients with Alzheimer's disease (AD) (onset age ≥ 85) with 162 less old patients (onset age < 85). Cognitive decline, ability to carry out activities of daily living (ADL), and overall severity were rated. BPSD were evaluated using a 16‐item questionnaire to the compare frequency of each symptom between old and very old groups. Results: Cognitive decline was equivocal in both old and very old groups. In contrast, very old patients were more impaired in ADL, and BPSD were more frequent in very old patients. Delusions, irritability, and delusional misidentification syndrome were frequent in both groups, but were more prominent in very old patients. Behavioral abnormalities such as excitement, delirium, reversed diurnal rhythm, and wandering were not prominent in old patients, but were frequent in very old patients. Conclusions: Very old AD patients presented more frequent BPSD than old AD patients. Troublesome behavioral abnormalities particularly prominent in the older patients might represent a heavy burden for caregivers.     

Acute hepatitis C transmitted by needlestick accident despite short duration interferon treatment

Hepatitis C virus (HCV) transmission by needlestick accidents involving hospital employees has become an important problem. The present report is of a case of acute hepatitis C that developed after a needlestick injury, despite short duration interferon treatment performed just after the accident in a trial effort to prevent HCV transmission. Nosocomial infection of HCV in medical employees is reviewed, and the current prospects for protecting them from HCV transmission after needlestick accident are discussed.     

Successful treatment of congenital pulmonary alveolar proteinosis with intravenous immunoglobulin G administration

Abstract:   The authors report a female patient with congenital pulmonary alveolar proteinosis (PAP). She had two brothers who died from the same disease. BAL did not improve her progressive respiratory failure. After intravenous immunoglobulin G (IVIG) administration for complicated hypogammaglobulinemia, she recovered from respiratory failure. The efficacy of IVIG was confirmed by recovery from deterioration in respiratory status and improvement in chest CT findings on two separate occasions. Subsequently, the patient remains free from respiratory symptoms for more than 3 years on an ongoing regimen of monthly IVIG. She had no surfactant protein (SP) B deficiency. Alveolar macrophages (AM) obtained from her BAL fluid were small and showed decreased phagocytotic activity. Immunostaining revealed weak expression of PU.1 in her AM, a key protein in AM maturation. All nucleotide sequences of granulocyte-macrophage colony stimulating factor (GM-CSF), GM-CSF-receptor and PU.1 were normal. Endotoxin-induced GM-CSF release from peripheral mononuclear cells (PMNC), and proliferation of PMNC in response to GM-CSF were normal. In addition, an antibody against GM-CSF, as seen in adult patients with idiopathic PAP, was not detected in the serum or BAL fluid. Although the patient's PMNC secreted only small amounts of IgG and IgM, an EB virus-derived cell line of her B cells secreted IgM as much as normal control cells. In a flow cytometric study, IgM was expressed on the cell surface. In conclusion, an abnormality in a single gene may have decreased secretion of immunoglobulin from the B cells and the AM phagocytotic activity in the patient.     

Intrahepatic expression of HBsAg and HBcAg in asymptomatic HBsAg carriers and its follow-up

Intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) was investigated in 46 asymptomatic HBsAg carriers by a direct immuno-fluorescent method. In 21 HBeAg positive carriers, HBsAg was expressed diffusely on the membrane of hepatocytes, with associated cytoplasmic localization in a few scattered hepato-cytes. HBcAg was expressed in the nucleus of many hepatocytes and in the cytoplasm of a few scattered hepatocytes, but not on the cell membrane. In 25 anti-HBe positive carriers, HBsAg was expressed on the surface and in the cytoplasm of hepatocytes diffusely and/or focally, but neither intrahepatic HBcAg nor serum HBV-DNA was detected. Repeat liver biopsies were performed in 17 patients. In eight of 13 HBeAg-positive HBsAg carriers, who developed histologically proven chronic hepatitis and liver cirrhosis, the localization of HBsAg in liver had changed from a membranous to a mixed (membrane and cytoplasm) pattern, and localization of HBcAg in liver had changed from a predominantly nuclear to a predominantly membranous and cytoplasmic pattern. However, in two HBeAg and two anti-HBe positive cases who showed no biochemical and histologic change at follow-up, the intrahepatic expressions of HBsAg and HBcAg in the second biopsies remained unchanged. Thus, decrease in membranous expression of HBsAg and increase in membranous and cytoplasmic expression of HBcAg were associated with progression to chronic liver disease. This suggests that membranous HBcAg may represent the major target in the process of injury to hepatocytes.