Cell division in the developing sympathetic nervous system

Summary Cell division in the rat superior cervical and stellate ganglia has been followed from 6 days before birth until 14 days after birth by [³H] thymidine autoradiography. Neuronal division ceased at the postnatal day 4 in superior cervical ganglia and postnatal day 3 in stellate ganglia, whereas division of non-neuronal cells continued throughout the entire period studied. Dividing cells in both ganglia were predominantly neuronal before birth and non-neuronal after the postnatal day 3.Nerve growth factor treatment resulted in an increase in the number of neurons in the ganglia when given either over the first four postnatal days while neuronal division was still occurring or from postnatal days 6–8 after neuronal division had ceased. The increase in neuron numbers was not due to increased neuronal division and was apparently due to an increased survival rate of differentiated neurons. An increase in the rate of division of non-neuronal cells accompanied the administration of nerve growth factor.     

Long-term bone marrow damage in experimental systems and in patients after radiation or chemotherapy

Long-term bone marrow damage, characterised by stem, progenitor and stromal cell abnormalities is a frequent occurrence after cytotoxic treatments. The relative contributions of each of these components are difficult to analyse, especially in the case of patients who have received combined chemotherapy. The damage may be latent, and not manifested in low numbers of mature functional cells in the blood, but may become apparent as an hypoplastic syndrome at later times. Little tendency of recovery to normal parameters is seen in experimental animals and in patients.     

Intussusception in children with ALL receiving chemotherapy for acute lymphoblastic leukaemia

Acute abdominal complications of chemotherapy are common but the differential diagnosis wide. We describe two cases of intussuception of the bowel in children receiving chemotherapy for acute lymphoblastic leukaemia (ALL) and discuss how a high clinical suspicion is critical for the correct diagnosis to be made rapidly.     

Late incidence and determinants of stroke after aortic and mitral valve replacement

Background

Stroke is a devastating complication in patients with prosthetic valves, but characterization of its late occurrence from a large cohort is lacking.

Methods

Three thousand one hundred eighty-nine adult patients who underwent a total of 3,576 operations for left-heart valve replacement were managed with contemporary anticoagulation guidelines and prospectively followed in a dedicated clinic. Total follow-up was 20,096 patient years. Bootstrapped survival analysis was used to determine the impact of patient and valve related factors on the incidence of stroke.

Results

Most strokes were embolic. Linearized embolic stroke rates were 1.3% ± 0.2% per year for aortic bioprostheses, 1.4% ± 0.2% per year for aortic mechanical valves, 1.3% ± 0.3% per year for mitral bioprostheses, and 2.3% ± 0.4% per year for mitral mechanical valves (p = 0.002, vs other implant types). Age more than 75 years, female gender, and smoking were independent risk factors after aortic and mitral valve replacement. Atrial fibrillation, coronary disease, and tilting-disc mechanical prostheses were independent predictors of embolic stroke after aortic valve replacement. Preoperative left ventricular (LV) dysfunction was an independent risk factor in patients with mitral prostheses. Primary operative indication, diabetes, redo status, or the presence of two prosthetic valves were not associated with an increased hazard. The addition of acetyl salicylic or dipyridamole to warfarin anticoagulation did not significantly lower embolic stroke risk in patients with mechanical prostheses.

Conclusions

Approximately 20% of patients with valve prostheses have an embolic stroke by 15 years after valve replacement. Some risk factors such as the avoidance of smoking, mitral mechanical prostheses, aortic tilting-disc valves, and proceeding to mitral surgery before LV dysfunction occurs are potentially modifiable.     

Infection with Ureaplasma urealyticum: is there a specific clinical and radiological course in the preterm infant?

BACKGROUND: Despite having mild early respiratory disease, many preterm babies develop chronic lung disease (CLD). Intrauterine infection with Ureaplasma urealyticum has been associated with preterm labour and CLD. OBJECTIVE: To test the hypothesis that infection with U urealyticum results in a specific clinical and radiological picture in the first 10 days of life. METHODS: Retrospective study of 60 ventilated babies < 30 weeks gestation, who had tracheal secretions tested for U urealyticum. Placental histology was reviewed by a paediatric pathologist for signs of chorioamnionitis. Chest radiographs were independently reviewed by two paediatric radiologists according to previously agreed criteria. All reviewers were blinded to the infection status of the babies. RESULTS: Twenty five babies were U urealyticum positive. These were more likely to experience chorioamnionitis (p = 0.004), premature rupture of membranes (p = 0.01), and spontaneous vaginal delivery (p = 0.09). U urealyticum positive babies had fewer signs of respiratory distress syndrome on early chest radiographs (p = 0.038), and they could be weaned from their ventilation settings (fraction of inspired oxygen (FIO(2)) and mean airway pressure) more quickly in the first few days. Subsequently U urealyticum positive babies deteriorated clinically and radiologically. More often they required ventilation to be restarted (p = 0.051), a higher proportion being ventilated on day 10 (p = 0.027) with higher FIO(2) (p = 0.001) and mean airway pressure (p = 0.002). Their chest radiographs showed more emphysematous changes as early as day 5 (p = 0.045), with a pronounced difference by day 10 (p = 0.009). CONCLUSIONS: Preterm ventilated babies with U urealyticum in their tracheal secretions have a different clinical and radiological course, with less acute lung disease but early onset of CLD, compared with those with negative cultures.     

Conjugated linoleic acid blocks estrogen signaling in human breast cancer cells

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid found in dairy products and meat from ruminants, has been widely shown to possess anticarcinogenic activity against breast cancer both in vitro and in animal models. However, little information is available concerning the mechanisms of the antitumor effects of these compounds. In this study, we investigated whether CLA has direct antiestrogenic activity in estrogen receptor positive (ER+) breast cancer cells. Treatment of the ER+ cell line, MCF-7, with 5 purified CLA isomers as well as "mixed" CLA showed a dose-dependent growth inhibition with the 9cis,11cis and 9cis,11trans being the most and least potent isomers, respectively. In assessing effects on a number of variables that play obligatory roles in the estrogen signaling pathway, we determined that CLA treatment downregulated ERalpha expression at both mRNA and protein levels and decreased binding activity of nuclear protein to a canonical estrogen response element (ERE(v)). Using a reporter gene construct (ERE(v)-tk-Luc) that was transiently transfected into MCF-7 cells, we also demonstrated inhibition of promoter activity by CLA that was directly mediated by blockage of activity through the ERE. The results indicated that the order of potency of the CLA isomers for inhibiting activation of ERE(v) was similar to that demonstrated for their antiproliferative activity on MCF-7 cells. Taken together, these findings demonstrate that CLA compounds possess potent antiestrogenic properties that may at least partly account for their antitumor activity on breast cancer cells.     

Electroconvulsive therapy in Scottish clinical practice: a national audit of demographics, standards, and outcome

OBJECTIVES: Many of the commonly expressed concerns about the effectiveness of electroconvulsive therapy (ECT) have been addressed by scientific studies. However, this has done little to reassure service users and the public at large about its use in routine clinical practice. This 3-year study between 1997 and 1999 consisted of a series of audit cycles to systematically answer questions about ECT demographics and outcome across Scotland. METHODS: Audit standards were agreed and each ECT clinic was visited at least twice to assess facilities and adherence to protocol as set down by the Royal College of Psychiatrists, UK. Demographics and outcome after ECT were measured during 2 9-month sample periods. Adequacy of teaching and supervision was assessed directly and by questionnaire. RESULTS: Facilities and equipment at ECT centers were up to date and generally of a high standard. ECT was given at a rate of 142 treatments per 100,000, mainly to white adult patients suffering from a depressive disorder. The ratio of females to males was approximately 2 to 1, and ECT was not given disproportionately to the elderly. 76% of patients were of informal status and 82% gave informed consent, with the remaining 18% receiving treatment under the safeguards of the Mental Health (Scotland) Act 1984. There was a definite clinical improvement with treatment, defined as at least a 50% fall in the Montgomery Asberg Depression Scale, in 71% of those treated for depressive illness. 65% of those treated for a non -depressive psychosis were rated as at least 'much improved' on the Clinical Global Impression scale. CONCLUSIONS: ECT given in routine clinical settings across Scotland meets Royal College of Psychiatrists standards and is an effective treatment of the clear majority of patients.     

Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine

The mechanism underlying the development of tolerance to morphine is still incompletely understood. Morphine binds to opioid receptors, which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins (G proteins). In this paper, we show that G(z), a member of the inhibitory G protein family, plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development. We blocked signaling through the G(z) second messenger cascade by genetic ablation of the alpha subunit of the G protein in mice. The Galpha(z) knockout mouse develops significantly increased tolerance to morphine, which depends on Galpha(z) gene dosage. Further experiments demonstrate that the enhanced morphine tolerance is not caused by pharmacokinetic and behavioural learning mechanisms. The results suggest that G(z) signaling pathways are involved in transducing the analgesic and lethality effects of morphine following chronic morphine treatment.