Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Inadequate dietary calcium and vitamin D intakes in renal-transplant recipients in Ireland.

OBJECTIVE: To quantify the dietary calcium and vitamin D intake in adult renal-transplant recipients attending at a large teaching hospital in Ireland for follow-up. SETTING: Outpatient renal-transplant follow-up clinic. SUBJECTS: Fifty-nine adult renal transplant recipients (58% male) with a mean age of 46 years, a median transplant duration of 6 years, and a mean estimated glomerular filtration rate (eGFR) of 50 mL/min per 1.73 m2. Fifty-three percent were at National Kidney Foundation stage 3 chronic kidney disease, and 14% had stage 4 chronic kidney disease. INTERVENTION: This cross-sectional, observational study used a tailored food frequency questionnaire specific for calcium and vitamin D intake in Irish adults, which was completed during a face-to-face interview with each subject. MAIN OUTCOME MEASURE: The main outcome measure was the average daily dietary and supplemented calcium and vitamin D intake. RESULTS: The median interquartile range (IQR) dietary calcium intake was 820 mg/day (range, 576-1,177 mg/day), and was similar in men and women (recommended intake > or = 1,000 mg/day in adult men and nonmenopausal adult women, > or = 1,500 mg/day in menopausal women). Five participants received calcium supplementation. Overall, 59% of men and 64% of women had total calcium intakes below the recommended amounts. The median IQR estimated dietary vitamin D intake was 5.2 microg/day (range, 2.4-6.4 microg/day) in women, and 4.6 microg/day (range, 2.2-6.6 microg/day) in men (recommended intake, > or = 10 microg/day). Six subjects received vitamin D supplementation. Total vitamin D intakes were suboptimal in 91% of men and 87% of women. Dietary calcium and vitamin D intakes significantly correlated with each other, but neither was significantly related to eGFR category, and was similarly low in both presumed menopausal women and in the initial year posttransplantation. CONCLUSION: These findings suggest that dietary and total calcium and vitamin D intakes in adult renal-transplant patients are in many cases inadequate.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

SCHWANN CELLS AND THE REGROWTH OF AXONS IN THE MAMMALIAN CNS: A REVIEW OF TRANSPLANTATION STUDIES IN THE RAT VISUAL SYSTEM

1. We have used peripheral nerve transplants or cultured Schwann cells grafted in association with different types of polymer to study axonal regrowth in the rat visual system. In some instances the glia were co-grafted with fetal tectal tissue. 2. The studies have two main aims: (i) to determine whether retinal axons can be induced to regrow at a site distant from their cell soma, that is, after damage to the brachial region of the optic tract; (ii) to determine whether retinal axons exposed to Schwann cells retain the ability to recognize their appropriate target neurons in CNS tissue. 3. In brachial lesion studies, Schwann cells were placed in the lesion site in association with nitrocellulose papers, within polycarbonate tubes in the presence or absence of a supporting extracellular matrix (ECM), or within polymer hydrogel scaffolds. Autologous sciatic nerve grafts were also used. Immuno-histochemical studies revealed the presence of regenerating axons within all polymer bridges. Regrowth of retinal axons was also seen, however, growth was not extensive and was limited to the proximal 1–1.5 mm of the implants. 4. In target innervation experiments, two surgical paradigms were developed. In one experiment, a segment of sciatic nerve was autografted onto the transected optic nerve in adult rats and the distal end of each graft was placed adjacent to fetal tectal (target) tissue implanted into the frontal cortex. To date, we have not been able to demonstrate selective recognition of target regions within tectal transplants by retinal axons exiting the sciatic nerve implants. 5. In the second experiment, Schwann cells were mixed with fetal tectal cells and co-grafted to the midbrain of newborn host rats. Schwann cells altered the characteristic pattern of host retinal growth into tectal grafts; in some cases axons were induced to grow away from appropriate target areas by nearby co-grafted Schwann cells. 6. In summary, Schwann cell/polymer scaffolds may provide a useful way of promoting the regrowth of damaged axons in the CNS, however: (i) in adults, at least, their effectiveness is reduced if they are located at a distance from the cell bodies giving rise to regenerating axons; (ii) in some circumstances exposure to a peripheral glial environment may affect the capacity of regenerating axons to recognize appropriate target cells in the CNS neuropil.     

N-methyl-D,L-aspartate elicits hypothalamic gonadotropin-releasing hormone release in prepubertal male rhesus monkeys (Macaca mulatta)

In higher primates, the protracted delay from infancy to puberty results from an interruption in hypothalamic GnRH release. To determine whether the quiescent hypothalamic GnRH neurons of the prepubertal macaque are capable of discharging the decapeptide in response to a generalized neural depolarization, an excitatory amino acid analog, N-methyl-D,L-aspartate (NMA), was administered systemically to orchidectomized rhesus monkeys between 13 and 20 months of age. GnRH secretion was estimated indirectly by monitoring changes in circulating LH concentrations after the responsivity of pituitary gonadotropes to GnRH had been greatly facilitated by the chronic intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every hour). The iv bolus administration of increasing doses of NMA (1.5, 4.8, and 15.0 mg/kg BW), 10-14 h after termination of the priming infusion of GnRH, elicited distinct discharges of LH, with magnitudes directly related to the amount of the excitant injected. Administration of a higher dose of NMA (48 mg/kg BW), however, failed to induce further LH release. The finding that pretreatment with a long-acting and potent GnRH receptor antagonist [( AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10] GnRH-HOAc) abolished the LH-releasing activity of NMA provides compelling evidence for the view that the action of the neural excitant to induce gonadotropin release was exerted at a suprapituitary level. The additional observation that an N-methyl-D-aspartate receptor antagonist (D,L-2-amino-5-phosphono-valeric acid) blocked the NMA-induced release of GnRH suggests that the amino acid analog interacted with the N-methyl-D-aspartate receptor on neurons that synthesize and/or control the release of the hypothalamic hormone. Most interestingly, three sequential GnRH discharges, with a period and an amplitude apparently similar to those generated by the hypothalamus of the adult, were elicited from the brain of prepubertal monkeys by the sequential administration of three injections of NMA at hourly intervals. Taken together these findings demonstrate that the apparent dormancy of hypothalamic GnRH neurons, which is characteristic of prepubertal development in higher primates and underlies the protracted delay in the onset of puberty in these species, may be readily terminated by application of a generalized neural excitation. Plasma FSH, PRL, GH, and cortisol concentrations were also monitored during the course of some of these experiments, and release of each of these four hormones was observed after the iv injection of NMA (15 mg/kg BW).     

Sarcoidosis and MIF gene polymorphism: a case-control study in an Irish population.

Macrophage migration inhibitory factor is a key pro-inflammatory mediator. A 5-CATT repeat functional polymorphism within the promoter of the gene was previously associated with the lowest promoter activity. It was hypothesised that patients exhibiting a 5-CATT allele would have a less aggressive inflammatory response with an associated less severe clinical phenotype in sarcoidosis. Irish Caucasian sarcoidosis patients (n = 173) followed up for 1-39 yrs and a control group (n = 166) were genotyped for the CATT repeat polymorphism. Disease severity at the time of diagnosis and at the time of elaboration of the present study was assessed by the presence of thoracic and extrathoracic symptoms, erythema nodosum, radiographic interstitial changes (chest radiograph score equal to stage II or greater, or high-resolution computed tomography confirmed), pulmonary function tests, steroid use, erythrocyte sedimentation rate, C-reactive protein and angiotensin-converting enzyme levels. In the Irish population studied, no evidence was found of a significant association between either sarcoidosis susceptibility and disease severity and the 5-CATT repeat functional polymorphism in the macrophage migration inhibitory gene. The present study found no significant association between the 5-CATT repeat macrophage migration inhibitory factor gene polymorphism and sarcoidosis, and did not support the overriding role for macrophage migration inhibitory factor in driving sarcoidosis pathogenesis.     

Urea rebound and delivered Kt/V determination with a continuous urea sensor

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.