Sleep-wake patterns of school-age children and adolescents before diagnosis and during induction chemotherapy for acute lymphocytic leukemia

Sleep disturbances are commonly reported by children receiving chemotherapy for leukemia. Sleep patterns before diagnosis and during induction chemotherapy were evaluated in 38 children (7 to 18 years?old). Child Sleep Assessment (CSA) was used to evaluate sleep patterns prior to diagnosis. Sleep diaries and actigraphy were used during chemotherapy. Adolescents went to bed later and awakened later than school-age children before diagnosis and during chemotherapy. During chemotherapy, children averaged 60 minutes of nighttime wake time. The early recognition of sleep problems associated with disease, treatment, and age is important for school-age children and adolescents with leukemia.     

Identification of dopamine, gonadotrophin-releasing hormone-I, and vasoactive intestinal peptide neurones activated by electrical stimulation to the medial preoptic area of the turkey hypothalamus: a potential reproductive neuroendocrine circuit

The neural and neurochemical substrates regulating reproduction in birds remain vaguely defined. The findings that electrical stimulation in the medial preoptic area (ES/MPOA) or intracerebroventricular infusion of dopamine (DA) stimulated luteinising hormone (LH) and prolactin (PRL) release in female turkeys, led to the suggestion that ES/MPOA might help to clarify the DA circuitry regulating LH and PRL. We used c-fos mRNA and tyrosine hydroxylase immunoreactivity as measured by double in situ hybridisation/immunocytochemistry (ISH/ICC) to determine which group/subgroup of DA neurones was activated following unilateral ES/MPOA. To establish that the reproductive neuroendocrine system was activated, double ISH/ICC was also conducted on c-fos/gonadotrophin-releasing hormone-I (GnRH-I) and c-fos/vasoactive intestinal peptide (VIP). Changes in circulating LH and PRL were determined by radioimmunoassay. Unilateral ES/MPOA (100 microA, right side) of anaesthetised laying turkeys for 30 min increased circulating LH and PRL levels. It also induced c-fos mRNA expression on the ipsilateral side by all GnRH-I neurones within the septopreoptic region, implying that GnRH-I neurones in this region share similar circuitry. VIP neurones within the nucleus infundibularis were the only VIP group to show c-fos mRNA expression, suggesting their involvement in ES/MPOA induced PRL release. c-fos mRNA expression was also observed in a subgroup of DA neurones in the nucleus mamillaris lateralis (ML). To our knowledge, the present study is the first to show that activation of DAergic cells in the ML is associated with the activation of GnRH-I and VIP neurones and the release of LH and PRL. It is likely that ES/MPOA activated VIP/GnRH-I neurones via activation of DA neurones in the ML, as this was the only DA subgroup that showed c-fos mRNA expression.     

Expression of D1 and D2 dopamine receptors in the hypothalamus and pituitary during the turkey reproductive cycle: colocalization with vasoactive intestinal peptide

The regulation of avian prolactin (PRL) secretion and PRL gene expression is influenced by hypothalamic vasoactive intestinal peptide (VIP), the PRL-releasing factor in avian species. Recent evidence indicates that D(1) and D(2) dopamine (DA) receptors play a pivotal role in VIP and PRL secretion. The differential expression of DA receptors located on hypothalamic VIP neurons and anterior pituitary cells may affect the degree of prolactinemia observed during the turkey reproductive cycle. The relative expression of D(1D) and D(2) DA receptor subtype mRNA was quantitated using in situ hybridization histochemistry (ISH). D(1D) and D(2) DA receptor mRNA was found expressed throughout the hypothalamus and pituitary. The expression of D(1D) DA receptor mRNA in the hypothalamus was found to be 6.8-fold greater than that of D(2) DA receptor mRNA. Higher D(1D) DA receptor mRNA content was found in the anterior hypothalamus (3.6-fold), the ventromedial nucleus (2.0-fold), the infundibular nuclear complex (INF; 1.9-fold), and the medial preoptic nucleus (1.5-fold) of laying hens as compared to that of reproductively quiescent non-photostimulated hens. The levels seen in incubating hyperprolactinemic hens were essentially the same as in laying hens, except for the INF where levels were 52% higher. During the photorefractory stage (hypoprolactinemia), the D(1D) DA receptor mRNA was at its lowest level in all areas tested. No differences were observed in hypothalamic D(2) DA receptor mRNA abundance throughout the reproductive cycle, except for an increase in D(2) DA receptor mRNA within the INF of photorefractory hens. Also, a marked reduction in D(2) DA receptor mRNA was observed in the pituitary of incubating hens. Pituitary D(1D) DA receptor levels did not change when birds entered the incubating phase. Double ISH revealed that D(1D) and D(2) DA receptor mRNAs were co-expressed within neurons expressing VIP mRNA, predominantly within the lateral hypothalamus and INF. D(1D) DA receptor mRNA was more highly expressed than D(2) DA receptor mRNA. The present findings clearly demonstrate that the expression of stimulatory D(1) DA receptor mRNA in the hypothalamus increases in hyperprolactinemic incubating hens, whereas inhibitory D(2) DA receptor mRNA increases in the pituitary of hypoprolactinemic photorefractory hens.     

Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria

Plasmodium falciparum in Thailand is multi-drug resistant. In a previous study it was shown that artesunate and mefloquine were effective, as follow up, we monitored the efficacy of this regimen for six years. During 1997-2002, 516 adult male volunteer patients in Chanthaburi Province were enrolled (50 patients in the first year, 400 patients in 1998-2001 and 66 patients in 2002). The symptom complex and parasite count (thick blood film) were monitored on days 0, 1, 2, 7, 14, 21, 28, 35 and 42. The dosages used were artesunate (ATS) 150 mg and mefloquine (M) 750 mg at hour 0 and ATS 100 mg and M 500 mg at hour 24. Their ages ranged from 30-35 years and their mean body weights were 54-56 kg. The presenting symptoms were fever 100%, headache 97-100%, anorexia 78-90%, and nausea 28-40%. The geometric mean of parasitemia ranged from 7,357-12,750/mm3. Defervescence in one day was found in 42-76% of patients and 85-100% in 2 days. The sensitivity (S) ranged from 87-94% and RI resistance (recrudescence) ranged from 6-13%. Forty patients demonstrated RI type of response, 37 were cured after being retreated with the same dosage and another 3 patients were cured after the third course of treatment. The aggravated adverse effects included vomiting (8-20%), anorexia (1-41%) and diarrhea (0-16%). These side effects were mild and transient. The efficacy of the artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria was high. The RI type of response was possibly due to re-infection or multiple broods and not to drug resistance. The adverse effects of anorexia, nausea, vomiting and diarrhea were mild and transient for mefloquine. The combination can be used as stand by treatment in areas of multi-drug resistant falciparum malaria.     

Vasoactive intestinal peptide and its role in continuous and seasonal reproduction in birds

Native Thai chicken, an equatorial species breeds throughout the year, whereas turkeys are seasonal temperate zone breeder whose reproductive cycle is terminated by the onset of photorefractoriness. This study investigated VIPergic activity throughout a reproductive cycle in both species, hypothesizing that the differential expression of vasoactive intestinal peptide (VIP) would provide an insight into the differing reproductive strategies of the two species. Distribution of VIP neurons in the native Thai chicken and a comparison of VIPergic activity in the nucleus inferioris hypothalami (IH) and nucleus infundibuli hypothalami (IN) were investigated. VIP immunoreactivity was found throughout the native Thai chicken brain, predominantly located within the IH-IN. The pattern of VIP distribution in the native Thai chicken supports the findings reported in temperate zone species. Unlike the turkey, where there is a dissociation between VIPergic activity and prolactin levels during photorefractoriness, in the native Thai chicken, which do not express photorefractoriness, changes in VIP immunoreactive (VIP-ir) neurons within the IH-IN were directly correlated with prolactin throughout the reproductive cycle. VIPergic activity reached its lowest level after hatching of the chicks in the native Thai chicken, while in the turkey VIPergic activity was lowest only after exposure to a short day photoperiod and the acquisition of photosensitivity. This suggests that VIP neurons in the IH-IN may play a pivotal role in regulating the reproductive cycle and its differential expression following hatching of the young may, in part, account for the difference in reproductive mode between equatorial, continually breeding, non-photoperiodic birds and seasonally breeding, photoperiodic birds.