Melatonin treatment for rhythm disorder

Abstract We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B₁₂, bright light therapy, or hypnotics. In one patient, melatonin 5–10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation

Carnitine (CAR) plays an important role in the β-oxidation of fatty acids. Less attention, however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.     

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.     

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.     

Polysomnography and body temperature changes by phototherapy in a delayed sleep phase syndrome case

Abstract We examined polysomnography (PSG) and body temperature in a patient with delayed sleep phase syndrome who responded to phototherapy. The patient was a 31-year-old woman whose condition had slightly improved by a vitamin B₁₂ administration. Phototherapy was administered to her in combination with the vitamin B₁₂ medication, and this combined treatment successfully advanced her delayed sleep phase. On PSG, the regimen showed shortened sleep latency, decreased total sleep time and stages 1 and 2 sleep, and increased slow wave sleep. Phototherapy also improved temporal distribution of delta half-waves (0.5-2.0 Hz, 31 µV) as well as phase relationship between sleep and body temperature.     

MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING

Six hundred and forty-three neonates from mothers with Graves' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6.0% (three of 50), 0.3% (one of 350), 1.7% (two of 117) and 0.0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P less than 0.01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.