Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

Abstract

Background: Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterised by progressive cerebellar ataxia, immunodeficiency, genetic instability, and cancer susceptibility. In addition, many patients suffer from growth failure. Methods: We analyzed growth and IGF-1/BP3 levels of 24 A-T-patients compared with an age-matched group of healthy controls (n?=?36). Results: Ten (41.7%) A-T patients and none of healthy controls had an IGF-1 level below the 3rd percentile for age. The growth hormone (GH) stimulation tests revealed a severe GH deficiency with no increase of >5?ng/ml in six of the ten A-T patients. The IGF-1 generation tests revealed normal increases in IGF-1 values in all patients. Conclusion: Our results show that a disturbance in the GH/IGF-1 axis was present in 58.3% of A-T patients. Low levels of GH were the result of reduced central GH secretion. GH treatment may be a therapeutic option for A-T patients with severe growth failure.     

Mental health nursing policy — an exploratory qualitative study of managers' opinions

Mental health nursing policy — an exploratory qualitative study of managers’ opinions During the 1990s, much of the legislation and policy that pertains to mental health services has sought to direct them towards a virtually exclusive concern with the seriously mentally ill, typified by the following recommendation from a recent Department of Health review of mental health nursing that stated: ‘The essential focus for the work of mental health nurses lies in working with people with serious or enduring mental illness’. On the other hand, pressure from the primary health care sector suggests the need for services to be provided for the less seriously mentally ill, particularly through the auspices of general practice fundholders. Following a review of the literature, a small-scale, exploratory study was initiated to seek answers to the following research question: How is the policy focus urging reorientation to the severely mentally ill viewed by nurse managers who have a responsibility through Mental Health Resource Centres and Community Mental Health Teams, to provide mental health services? The study was based within a Welsh National Health Service (NHS) Trust that employed six nurse managers of Community Mental Health Teams (CMHTs). Four of the managers additionally had responsibility for Community Mental Health Resource Centres (CMHRCs). Of the population of six managers, four composed the sample for the investigation. A qualitative research approach was employed, utilizing semistructured interviews as the data collection tool. Analysis of the data revealed that managers were finding creative solutions in order to meet the conflicting demands placed upon them. The research findings also indicated that many of the obstacles to providing a needs-led service were structural in origin, and could be resolved by central strategic intervention.     

Head and pelvic movements during a dynamic reaching task in sitting: Implications for physical therapists

OBJECTIVES: To describe the distance reached, speed, and movement of the head and pelvis of healthy volunteers; to describe any influence of age on these variables; and to compare healthy volunteers and subjects with hemiplegia while performing a seated reaching task. DESIGN: Age-matched, case-control study. SETTING: Gait laboratory in a general hospital. PARTICIPANTS: A convenience sample of 53 healthy volunteers (30 women; 23 men; mean age, 57yr; range, 30-79yr) and 5 subjects with hemiplegia (2 women, 3 men; mean age, 65yr; range, 60-78yr) were recruited within 6 weeks poststroke. INTERVENTIONS: Participants sat on a bench with feet supported and reached laterally as far as they could without falling. MAIN OUTCOME MEASURES: The speed, distance reached, and angular movements of the head and pelvis were recorded by using the 3-dimensional movement analysis system. RESULTS: A significant age-related reduction in the distance reached (p < .001), velocity of the movement (p =.000), and pelvic tilt used (p < .01) was found among healthy volunteers. Comparison of data from healthy volunteers and subjects with hemiplegia showed a significant reduction in the angular movements of the heads of subjects with hemiplegia. CONCLUSIONS: The findings suggest conservation of movement with increasing age and stroke. This movement reduction could have negative effects on a subject's ability to make postural changes in response to disturbance and activity. Such information may assist therapists to gain insight into the nature of balance deficits and the adaptive behavior that could result.     

Comparison of rates and risk factors for development of anaemia and erythropoiesis-stimulating agent utilization after radical or partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The consequences and significance of iatrogenically‐induced CKD are poorly understood. Most data regarding risk of CKD and its complications are inferred from the medical literature. This is the first study to examine impact of surgical management of renal masses on development of anaemia. Patients who underwent radical nephrectomy had a significantly higher incidence of anaemia and ESA utilization than a contemporary well‐matched cohort that underwent partial nephrectomy. The results obtained add to the growing body of data supporting the use of partial nephrectomy in the management of clinically appropriate renal masses.

OBJECTIVE

• ? To examine the incidence of and risk factors for the development of anaemia and erythropoiesis‐stimulation agent (ESA) treatment in patients undergoing radical nephrectomy (RN) and partial nephrectomy (PN) because anaemia is a significant cause of morbidity in chronic kidney disease.

PATIENTS AND METHODS

• ? The study comprised a retrospective review of 905 patients (610 RN/295 PN; mean age, 57.5 years; mean follow‐up, 6.4 years) who underwent surgery for renal tumours at two institutions from July 1987 to June 2007.
• ? Demographics, disease characteristics and pre‐ and postoperative (i.e. renal function, metabolic parameters, anaemia and ESA treatment) were recorded.
• ? Data were analyzed within subgroups based on treatment (RN vs PN).
• ? Multivariate analysis was conducted to determine the risk factors for developing anaemia after surgery.

RESULTS

• ? Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P < 0.001). No significant differences were noted with respect to demographics and preoperative anaemia (RN 16.4% vs PN 18.6%; P= 0.454) and ESA‐treatment (RN 0.7% vs PN 1.4%; P= 0.499).
• ? After surgery, significantly less de novo anaemia (PN 4.1% vs RN 17.5%; P < 0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P < 0.001) occurred in the PN cohort.
• ? Multivariate analysis showed that age ≥60 years (odds ratio, OR, 1.62; P= 0.008), African American ethnicity (OR, 2.30; P < 0.001), smoking (OR, 1.60; P= 0.013), glomerular filtration rate (GFR) <60 mL/min/1.73 m² (OR, 4.09; P < 0.001), ≥1+ proteinuria (OR, 2.19; P < 0.03), metabolic acidosis (OR, 4.08; P= 0.007) and RN (OR, 2.58; P < 0.001) were significantly associated with de novo anaemia.

CONCLUSIONS

• ? Patients who underwent RN had a significantly higher prevalence of anaemia and ESA‐treatment compared to a well‐matched cohort that underwent PN.
• ? In addition to RN, age ≥60 years, African American ethnicity, history of smoking, GFR < 60 mL/min/1.73 m², proteinuria and metabolic acidosis were associated with developing anaemia.

     

LS8 cell apoptosis induced by NaF through p-ERK and p-JNK – a mechanism study of dental fluorosis

Objective: To investigate the possible biological mechanism of dental fluorosis at a molecular level.

Material and methods: Cultured LS8 were incubated with serum-free medium containing selected concentrations of NaF (0?～?2?mM) for either 24 or 48?h. Subcellular microanatomy was characterized using TEM; meanwhile, selected biomolecules were analysed using various biochemistry techniques. Transient transfection was used to modulate a molecular pathway for apoptosis.

Results: Apoptosis of LS8 was induced by NaF treatment that showed both time and concentration dependency. The activity of caspase-3, -8, -9 was found to be increased with NaF in a dose-dependent manner. Western blot revealed that the protein expression of p-ERK and p-JNK were decreased, while the expression of p-P38 was increased. Inhibition of the p-ERK and p-JNK pathways resulted in a similar decrease for caspase-3.

Conclusion: During NaF-induced apoptosis of LS8, p-ERK and p-JNK were closely associated with induction of apoptosis, which might be a mechanism of dental fluorosis.     

Hypoxia increases the expression of enamel genes and cytokines in an ameloblast‐derived cell line

The aim of this study was to investigate the effect of hypoxic conditions on the expression of enamel genes and on the secretion of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cytokines, and interleukins by an ameloblast‐derived cell line. Murine ameloblast‐derived cells (LS‐8 cells) were exposed to 1% oxygen for 24 and 48 h and harvested after 1, 2, 3, and 7 d. The effect of culture in hypoxic conditions on the expression of structural enamel matrix genes and on the secretion of cytokines and interleukins, as well as ALP and LDH, into the cell‐culture medium was calculated relative to the expression and secretion of these factors by untreated cells (controls) at each time point. Hypoxia increased expression of the structural enamel matrix genes amelogenin (Amelx), ameloblastin (Ambn), and enamelin (Enam), and the enamel protease matrix metalloproteinase‐20 (Mmp20). Expression of hypoxia‐inducible factor 1‐alpha (Hif1α), and secretion of several vascularization factors and pro‐inflammatory factors, were increased after 24 and 48 h of hypoxia. The ALP activity was reduced after 24 and 48 h of hypoxia, whereas the LDH level in the cell‐culture medium was higher after 24 h of hypoxic conditions compared with 48 h. In conclusion, hypoxic exposure may disrupt the controlled fine‐tuned expression and processing of enamel genes, and promote the secretion of pro‐inflammatory factors.