Reduced exertion high-intensity interval training (REHIT) in an adult with Cystic Fibrosis: A mixed-methods case study.

Although aerobic capacity has been identified as an important predictor of mortality in Cystic Fibrosis (CF) individuals, many remain insufficiently active. As a 'lack of time' is a commonly cited barrier to exercise, reduced-exertion high-intensity interval training (REHIT) may provide a truly time-effective method to increase aerobic capacity. Six-weeks of REHIT in a CF individual was assessed by a cardiopulmonary exercise test (CPET) and individual perceptions described using a self-report narrative. Peak oxygen uptake ( V ˙ O2peak) increased by 6% whilst pulmonary function remained unchanged. Qualitative data indicated social support and low-time commitment positively influenced adherence with fatigue and lack of enjoyment noted as a significant barriers. REHIT was demonstrated as a viable, manageable option for a CF individual with moderate-severe pulmonary limitation. Further research is needed to determine the efficacy of REHIT in a large representative sample to ascertain whether it represents an alternative treatment strategy.

Using photo-elicitation to explore perceptions of physical activity among young people with cystic fibrosis.

BACKGROUND: Physical activity is recommended in the management of cystic fibrosis (CF). The aim of this study was to explore motives, barriers and enablers to physical activity among this population. METHODS: Twelve participants (12-18 years) were recruited via convenience sampling. Photo-elicitation alongside semi-structured interviews were used to explore participants' views and experiences of physical activity. RESULTS: Our findings revealed motives for physical activity including health, enjoyment and autonomy. Those with families who valued physical activity tended to have positive attitudes towards physical activity, and valued and integrated it into their lives. Moreover, they were likely to be intrinsically motivated to be active. Several factors enable and act as barriers to physical activity. Whilst CF influenced physical activity, the majority of enablers and barriers raised where congruent with the general populations. CONCLUSION: This study provides support that healthcare providers should encourage both young people with CF and their families to be active, and subsequently informs the development of clinical interventions to support physical activity among young people with CF and their families.

Kinetics of trace element uptake and release by particles in estuarine waters: effects of pH, salinity, and particle loading.

The uptake and release of 109Cd, 51Cr, 60Co, 59Fe, 54Mn, and 65Zn were studied using end-member waters and particles from Port Jackson estuary, Australia. The kinetics of adsorption and desorption were studied as a function of suspended particulate matter (SPM) loading and salinity. Batch experiments showed that the position and slope of the pH edges are dependent on the metal and on the salinity of the water (except for Mn). The general effect of salinity was to move the adsorption edge to higher pH values, with the greatest change being found for Cd. Most of the metals showed relatively simple kinetics with an increase in uptake as a function of time and suspended particle concentrations. The time dependence of Cd uptake was more complex, with an initial adsorption phase being followed by strong mobilization from the suspended sediments, explained by chlorocomplexation and competition with seawater major cations. The reversibility of the sorption decreased in the order Co>Mn>Zn>Cd>Fe>Cr. The percentage of adsorbed metal released in desorption experiments was greater in seawater than freshwater for Cd, Zn, and Co. These results are important in understanding the cycling of pollutants in response to pH, salinity, and particle concentrations in estuarine environments. In addition, they give valuable insight into the important mechanisms controlling the partitioning of heavy metals in the Port Jackson estuary.

Kinetics and thermodynamics of beta 2-microglobulin binding to the alpha 3 domain of major histocompatibility complex class I heavy chain.

The major histocompatibility complex (MHC) class I molecule plays a crucial role in cytotoxic lymphocyte function. Functional class I MHC exists as a heterotrimer consisting of the MHC class I heavy chain, an antigenic peptide fragment, and beta2-microglobulin (beta2m). beta2m has been previously shown to play an important role in the folding of the MHC heavy chain without continued beta2m association with the MHC complex. Therefore, beta2m is both a structural component of the MHC complex and a chaperone-like molecule for MHC folding. In this study we provide data supporting a model in which the chaperone-like role of beta2m is dependent on initial binding to only one of the two beta2m interfaces with class 1 heavy chain. beta2-Microglobulin binding to an isolated alpha3 domain of the class I MHC heavy chain accurately models the biochemistry and thermodynamics of beta2m-driven refolding. Our results explain a 1000-fold discrepancy between beta2m binding and refolding of MHC1. The biochemical study of the individual domains of complex molecules is an important strategy for understanding their dynamic structure and multiple functions.

The quantification of technetium in generator-derived pertechnetate using ICP-MS.

Previous analytical methods employed to measure 99Tc:99mTc ratios in chromatographic 99mTc generators, derived from fission-based 99Mo, were limited in monitoring the ratios in low activity generators, over the extent of their elution regimes. For regulatory purposes, ICP-MS was employed to measure total technetium in generator eluates down to a level of 200 pg ml(-1) (200 ppt). Measured 99Tc:99mTc ratios compared very well with the theoretically computed values, ranging from 47:1 for a first elution of a generator with a long ingrowth time to 1.4:1 for the 17th elution of a generator with a short ingrowth time.

Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization.

OBJECTIVE: To assess the endocrine and clinical responses to microdose GnRH agonist (GnRH-a) that was administered in the early follicular phase before controlled ovarian hyperstimulation to poor responders who were candidates for IVF-ET. DESIGN: Prospective nonrandomized trial with historical controls. SETTING: Tertiary care university-affiliated infertility practice. PATIENT(S): Thirty-four IVF-ET candidates with a prior poor response to a standard long-protocol GnRH-a controlled ovarian hyperstimulation regimen (cycle A). Patients were divided into two groups based on their age at the initiation of cycle A (Group 1: < or = 39 years, n = 15; Group 2: > or = 40 years, n = 19). INTERVENTION(S): Low-dose oral contraceptive (x 21 d) followed by GnRH-a (leuprolide acetate; 40 micrograms s.c. b.i.d.) flare and urofollitropin initiated on day 3 of GnRH-a administration (cycle B). MAIN OUTCOME MEASURE(S): Comparative analysis of clinical responses (total urofollitropin dose used and number of oocytes retrieved as well as fertilization and clinical and ongoing pregnancy rates) and endocrine responses (serum E2, FSH, LH, T, and P levels) between cycles A and B in the two groups. Early follicular phase serum E2 and FSH changes in groups 1 and 2 were compared with changes in nine normal responder controls who were receiving a standard long-protocol GnRH-a/urofollitropin regimen (group 3). RESULT(S): Maximal E2 levels as well as clinical and ongoing pregnancy rates were higher in cycle B patients receiving microdose GnRH-a. Cancellation rates in cycle B were lower than in cycle A. Statistically significant increases in treatment day 6 serum FSH levels were noted during cycle B in both groups 1 and 2 but not in group 3 controls. No abnormal rises in LH, P, or T were noted in any of the groups. CONCLUSION(S): Microdose GnRH-a enhances urofollitropin response and clinical outcome in poor responders undergoing IVF-ET. This may be due to enhanced release of early follicular phase endogenous FSH without concomitant deleterious rises in androgen levels or corpus luteum rescue.

Differential expression of the murine eukaryotic translation initiation factor isogenes eIF4A(I) and eIF4A(II) is dependent upon cellular growth status.

The murine translation initiation factor eIF4A is encoded by two genes: eIF4A(I), expressed in all mouse tissues, and eIF4A(II), a gene preferentially expressed in organs with low proliferative capacity. To investigate the hypothesis that regulation of the eIF4A isogenes is dependent upon cellular growth status, steady state expression of eIF4A(I) and eIF4A(II) mRNAs was quantitated in asynchronous cell populations and in cultures synchronized by nutrient starvation. Our data showed that changes in cell growth state were responsible for striking differences in eIF4A isogene-specific regulation. eIF4A(I) mRNA was 10-fold more abundant than eIF4A(II) in growing cells. In growth arrested cells eIF4A(I) mRNA levels remained unchanged, whereas eIF4A(II) mRNA levels increased approximately 3-fold. Following serum stimulation of growth arrested cells, eIF4A(I) mRNA levels increased 3- to 10-fold; conversely, eIF4A(II) mRNA levels decreased 2- to 3-fold. Thus, eIF4A(I) mRNA is synthesized and translated most efficiently in growing cells while eIF4A(II) mRNA synthesis and translation is associated preferentially with the growth-arrested (quiescent) state. This difference in expression patterns likely enables the cell to maintain required levels of this factor throughout its life cycle.

The digestive strategy of the common marmoset, Callithrix jacchus.

Digestive tract morphology and function were studied in the common marmoset (Callithrix jacchus), a small (350 g) exudivore with a well-developed caecum. Transit times (times of first appearance of the markers in the faeces following a pulse dose in the food) were similar for Co-EDTA, which marks the fluid phase of the digesta, and Cr-mordanted cell walls, which marked the large (600-1200 microns) particulate phase of the digesta. However, mean retention time (the average time taken for the markers to transverse the whole digestive tract) for Co-EDTA was significantly longer than for Cr-cell walls, indicating selective retention of fluid digesta relative to large particles, probably in the caecum. These data are consistent with a digestive strategy of the common marmoset that appears to be based on rapid digestion of higher quality foods (animal prey, fruits) in the small intestine, followed by microbial fermentation of the complex polysaccharides of plant exudates in the caecum, which would allow for considerable dietary flexibility in its natural habitat of scrub forests.

Digestive performance and selective digesta retention in the long-nosed bandicoot, Perameles nasuta, a small omnivorous marsupial.

Bandicoots are opportunistic omnivores that feed on invertebrates, fungi and both epigeal and hypogeal plant parts. We examined the performance of the digestive tract of the long-nosed bandicoot (Perameles nasuta) in terms of intake and total digestibility, patterns of excretion of inert digesta markers, and likely sites of digesta retention, on two diets designed to mimic part of their natural plant and insect diets. On the insect diet (mealworm larvae), bandicoots virtually maintained body mass at a digestible energy intake of 511 kJ.kg-0.75.day-1 and were in strongly positive nitrogen balance. In contrast, on the plant diet (shredded sweet potato), bandicoots ate only one-third as much digestible energy, lost 7% body mass, and were in negative nitrogen balance. Mean retention times of two particle markers on the plant diet (27.5 and 27.0 h) were more than double those on the insect diet (12.4 and 11.2 h), and on both diets the mean retention time of the fluid digesta marker was greater than those of the particle markers, indicating consistent selective retention of fluid digesta in the gut. It was seen radiographically than in mealworm-fed bandicoots major sites of digesta retention were the distal colon and rectum, whereas in the sweet potato-fed animals the caecum and proximal colon were principal sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of gamma-hexachlorocyclohexane (lindane) to determine the ontogeny of metabolism in the developing rat.

The compound lindane (gamma-hexachlorocyclohexane) has been used to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic fate of lindane at 2, 9, 16, and 23 d of age was investigated following subcutaneous administration of lindane at 20 mg/kg containing 0.5 microCi [U-14C]lindane in peanut oil. Groups of 10 pups (5 male and 5 female) were sacrificed at 4-h intervals during the 24-h period following dosing. Adrenals, blood, brain, heart, lung, liver, and kidneys were analyzed for radioactivity. Urine samples were analyzed for radioactivity and metabolites of lindane. There was a significant age-dependent increase in the metabolism of lindane in the rat. High levels of radioactivity in the lung and increased reductive dechlorination suggest that the lung may play a greater role in metabolism of lindane by young rats. Oxidative phase I reactions increased significantly, while anaerobic reductive dechlorination of lindane to 4-chlorophenylmercapturic acid decreased significantly with age. Phase II sulfate and glutathione conjugations decreased significantly and glucuronide conjugation increased significantly with age. Metabolism and excretion of lindane appear to parallel development of the hepatic enzymes involved in phase I and phase II reactions.

Fourier transform infrared studies of ribonuclease in H2O and 2H2O solutions.

Fourier transform infrared transmission spectra have been obtained of the enzyme ribonuclease in both H2O and 2H2O. The resolution of the spectra have been enhanced by Fourier self-deconvolution procedures. The infrared spectrum of ribonuclease changes during exchange of the enzyme's amide hydrogens for deuterium and the exchange has been followed in the amide I and amide II spectral regions. The amide I band shifts towards lower wavenumbers during both the fast and slow phases of hydrogen exchange and the interpretation of these shifts has aided the band assignments. In particular these studies have allowed an assignment to be made for the high frequency component of the beta-strand absorption that differs from that proposed previously. This paper represents the first example of the use of deconvoluted Fourier transform infrared spectra in conjunction with hydrogen-deuterium exchange in order to aid in the assignment of a protein's infrared bands.

Management of pancreatic and duodenal trauma.

Eighty-four patients were treated for pancreatic or duodenal injuries or both over a 13 year period. Isolated contusion of the duodenum was managed by drainage only, and disruption was managed with primary closure, coverage of the closure with a serosal patch, and drainage. Patients with distal pancreatic injuries that involved the body or tail of the pancreas and were total or near-total transections underwent distal pancreatectomy and splenectomy. The difficult areas of management continue to be the type III and IV pancreatic and duodenal injuries. Extensive pancreatic resection should be reserved for those situations in which the pancreas has been devitalized and it is not expected that resolution will occur with drainage. The mortality in combined severe pancreatic and duodenal injuries was 64 percent with death related to associated injuries in most cases; however, extensive resection (Whipple procedure) in two cases led to death because of leakage from the anastomosis with subsequent retroperitoneal infection. Postoperative management of patients with pancreatic and duodenal injuries should always include careful attention to nutrition.

Effect of pregnancy and nursing on the growth of metastases from N-nitroso-N-methylurea-induced mammary carcinomas.

Pregnancy increased the survival times of inbred BUF/N rats bearing occult metastasis of a mammary carcinoma at the time of conception. Nursing following delivery nullified the effect of pregnancy. The similarity of the controlled experimental data with the limited clinical observations is noted. An experimental model of rat mammary carcinoma has been described that possesses a highly metastasizing capacity and can be utilized to study the behavior of clinically silent metastasis.

Azaserine: further evidence for DNA damage in Escherichia coli.

Azaserine causes DNA damage in stationary-phase cells. In our investigation of this damage, we used strains of Escherichia coli differing in repair capabilities to study azaserine-induced DNA damage, detected as DNA strand breaks by sucrose gradient sedimentation techniques. Reduced sedimentation in alkaline and neutral sucrose gradients indicated the presence of both alkali-labile sites and in situ strand breaks. Azaserine induced DNA single-strand breaks (SSBs) abundantly in all but the recA strain, in which SSBs were greatly reduced. Treatment of purified DNA with azaserine from bacteriophages T4 and PM2 produced no detectable SSBs. Several other studies also failed to detect DNA damage induced directly by azaserine. Increased levels of beta-galactosidase were induced in an E. coli strain possessing a rec::lac fusion, providing further evidence for azaserine induction of the recA gene product. In addition, azaserine induced adaptation against killing but not against mutagenesis in wild-type E. coli strain.

Role of AP endonuclease in DNA breakage and cell inactivation of Escherichia coli subjected to mild heat (52 degrees C).

The molecular mechanism of DNA injury by mild heat was investigated using matched isogenic mutants of E. coli. On heating at 52 degrees C for 1 h, the number of DNA single-strand breaks (SSBs) detected by the alkaline sucrose gradient sedimentation technique was consistently smaller in mutants NH5016 and BW2001, both deficient in the AP (apurinic/apyrimidinic) endonuclease of exonuclease III, as compared with their wild-type parent AB1157. The greater number of SSBs in the wild type was accompanied by more extensive cell death as compared with the AP-deficient mutants. Heating of endonuclease-free DNA systems, viz., T4 phage and T4 DNA, at 52 degrees C for up to 4 h did not result in any detectable SSB. Apparently, cellular injury by mild heat is self-inflicted through an AP-endonuclease-mediated process and hence depends on the cell's genetic complement of AP endonuclease. Mild heat is believed to activate the nucleolytic attack, and the resultant DNA-strand breaks, if not repaired, will eventually lead to cell death.

Cardiopulmonary resuscitation by medical and surgical house-officers.

In teaching hospitals the responsibility for cardiopulmonary resuscitation usually rests with the house-staff, yet most house-officers receive no formal training in life support. The life-support skills of 45 medical and surgical house-officers in a university teaching hospital were tested by means of simulated cardiac arrests. House-officers were graded on the basis of a performance checklist derived from the standards of the American Heart Association. No house-officer received a pass score in basic life support (BLS). Only 29% could properly compress and ventilate the mannequin. In advanced cardiac life support (ACLS) only one-third could intubate in 35 s or less; only 31%, 40%, and 33% could manage ventricular fibrillation, asystole, and complete heart block, respectively. Some house-officers were unable to operate the defibrillator or assemble resuscitation equipment. Many house-officers displayed helplessness and anxiety during the simulations; fourteen (40%) were prompted to register for additional advanced life-support courses. The performance of medical and surgical house-officers was equal. House-officers who had received prior life-support training performed better in BLS (p less than 0.001) but not in ACLS. It was concluded that (a) most medical and surgical house-officers are not reasonably proficient in BLS and ACLS, and (b) cardiac arrest simulation is a motivating exercise which permits analysis of each house-officer's life-support skills. House-officers should have more training and practice in life support, or they should not have primary responsibility for cardiopulmonary resuscitations.