Human granulocytes generated in continuous bone marrow culture are physiologically normal

A long-term bone marrow culture system has been derived for maintenance and proliferation of human hemopoietic stem cells and granulocytes in vitro for up to 20 wk. The granulocytes generated in these cultures at 8 wk were comparable to fresh human peripheral blood granulocytes in physiologic properties, including phagocytosis, degranulation, respiratory burst, and bacterial killing: individual granulocytes generated up to 20 wk in several cultures demonstrated normal superoxide-generating capacity by NBT dye reduction slide test. Thus, human granulocytes generated in continuous marrow culture retain many biologic functions associated with bacterocidal capacity in vivo and indicate that this system should be of value in studies of disorders of granulocyte differentiation.     

The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults

OBJECTIVE: Disasters are associated with increased risk of posttraumatic stress disorder (PTSD) and major depression, but no study, to the authors' knowledge, has determined whether genotype interacts with disaster exposure and social support to moderate risk of these phenotypes. The authors tested the hypothesis that a polymorphism in the serotonin transporter gene (locus, SLC6A4; variant, serotonin 5-HTTLPR) moderates risk of posthurricane PTSD and major depression given high hurricane exposure and low social support. METHOD: The authors interviewed a household probability sample of adults 6-9 months after the 2004 hurricanes about hurricane exposure, social support, and posthurricane PTSD and major depression. DNA was collected from a subset of participants. Participants were 589 adults ages 18 and older from 38 Florida counties who provided valid DNA samples. Outcome measures were DSM-IV diagnoses of posthurricane PTSD and major depression derived from structured interviews. RESULTS: The low-expression variant of the 5-HTTLPR polymorphism increased risk of posthurricane PTSD and major depression but only under the conditions of high hurricane exposure and low social support after adjustment for sex, ancestry (as determined by Bayesian clustering of genotypes), and age. Similar effects were found for major depression. High-risk individuals (high hurricane exposure, the low-expression 5-HTTLPR variant, low social support) were at 4.5 times the risk of developing PTSD and major depression of low-risk individuals. CONCLUSIONS: The low-expression variant of the 5-HTTLPR polymorphism modifies risk of postdisaster PTSD and major depression under conditions of high hurricane exposure and low social support, confirming and extending previous research.     

Prostanoid receptor antagonists: development strategies and therapeutic applications

Background and purpose:

Histamine H₃ receptor antagonists are currently being evaluated in clinical trials for a number of central nervous system disorders including narcolepsy. These agents can increase wakefulness (W) in cats and rodents following acute administration, but their effects after repeat dosing have not been reported previously.

Experimental approach:

EEG and EMG recordings were used to investigate the effects of acute and repeat administration of the novel H₃ antagonist GSK189254 on the sleep–wake cycle in wild-type (Ox+/+) and orexin knockout (Ox−/−) mice, the latter being genetically susceptible to narcoleptic episodes. In addition, we investigated H₃ and H₁ receptor expression in this model using radioligand binding and autoradiography.

Key results:

In Ox+/+ and Ox−/− mice, acute administration of GSK189254 (3 and 10 mg·kg⁻¹ p.o.) increased W and decreased slow wave and paradoxical sleep to a similar degree to modafinil (64 mg·kg⁻¹), while it reduced narcoleptic episodes in Ox−/− mice. After twice daily dosing for 8 days, the effect of GSK189254 (10 mg·kg⁻¹) on W in both Ox+/+ and Ox−/− mice was significantly reduced, while the effect on narcoleptic episodes in Ox−/− mice was significantly increased. Binding studies revealed no significant differences in H₃ or H₁ receptor expression between Ox+/+ and Ox−/− mice.

Conclusions and implications:

These studies provide further evidence to support the potential use of H₃ antagonists in the treatment of narcolepsy and excessive daytime sleepiness. Moreover, the differential effects observed on W and narcoleptic episodes following repeat dosing could have important implications in clinical studies.     

Waist circumference in relation to body perception reported by Finnish adolescent girls and their mothers

Aim: To study how waist circumference (WC) relates to body perception in adolescent girls and to maternal perception of the girl's body size.
Methods: Three hundred and four girls, 11–18 years, were measured for height, weight and WC. 294 girls provided self-report data on weight, height and body image before anthropometric measurements. Paired data from 237 girls and mothers on perception of the girls' body size were collected.
Results: In girls, self-reported weight indicated awareness of actual body size. The girls' body perception showed an overestimation of body size relative to international reference values for body mass index (BMI) (p < 0.05), but not for WC. Girls' body perception exceeded that of their mothers (p < 0.05). Maternal perception agreed better than the girls' perception with international reference values for BMI (p < 0.05). No significant difference between mothers and girls were found concerning agreement of body perception with international reference values for WC.
Conclusion: WC rather than BMI agrees with perception of body size, possibly due to its relation to abdominal fat at different ages. For effective prevention and treatment programmes for weight-related health problems among adolescent girls, we recommend measuring WC to diminish the discrepancy between measured and perceived body size.     

Successful treatment of aortic thrombosis after umbilical catheterization with tissue plasminogen activator

An infant presented 10 days after removal of a high umbilical arterial catheter with total occlusion of the distal abdominal aorta. Complete dissolution was achieved with a combination of iv tissue plasminogen activator and heparin. Ultrasound examination confirmed the diagnosis and subsequent resolution of the thrombus.     

Hyaline membrane disease, alkali, and intraventricular haemorrhage

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.