Immersion of debrided diabetic foot ulcer tissue in electrochemically generated pH neutral hypochlorous acid significantly reduces the microbial bioburden: whole-genome sequencing of Staphylococcus aureus, the most prevalent species recovered.

BACKGROUND: Diabetic foot ulcer infections (DFUIs) are the leading cause of lower-limb amputations, mediated predominantly by Staphylococcus aureus. pH-neutral electrochemically generated hypochlorous acid (anolyte) is a non-toxic, microbiocidal agent with significant potential for wound disinfection. AIMS: To investigate both the effectiveness of anolyte for microbial bioburden reduction in debrided ulcer tissues and the population of resident S. aureus. METHODS: Fifty-one debrided tissues from 30 people with type II diabetes were aliquoted by wet weight and immersed in 1- or 10-mL volumes of anolyte (200 parts per million) or saline for 3 min. Microbial loads recovered were determined in colony forming units/g (cfu/g) of tissue following aerobic, anaerobic and staphylococcal-selective culture. Bacterial species were identified and 50 S. aureus isolates from 30 tissues underwent whole-genome sequencing (WGS). FINDINGS: The ulcers were predominantly superficial, lacking signs of infection (39/51, 76.5%). Of the 42/51 saline-treated tissues yielding ≥105 cfu/g, a microbial threshold reported to impede wound-healing, only 4/42 (9.5%) were clinically diagnosed DFUIs. Microbial loads from anolyte-treated tissues were significantly lower than saline-treated tissues using 1 mL (1065-fold, 2.0 log) and 10 mL (8216-fold, 2.1 log) immersion volumes (P<0.0005). S. aureus was the predominant species recovered (44/51, 86.3%) and 50 isolates underwent WGS. All were meticillin susceptible and comprised 12 sequence types (STs), predominantly ST1, ST5 and ST15. Whole-genome multi-locus sequence typing identified three clusters of closely related isolates from 10 patients indicating inter-patient transmission. CONCLUSIONS: Short immersions of debrided ulcer tissue in anolyte significantly reduced microbial bioburden: a potential novel DFUI treatment.

Reclassification as NIFTP: a Retrospective Review in a Single Institution with an Emphasis on Workload.

The aim of this study was to determine the number of cases of papillary thyroid carcinoma (PTC) which could be reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in our institute over a 10-year period, document their clinical status and assess the number of slides that had to be reviewed per case to exclude NIFTP. The histopathology reports for thyroid resections for all papillary carcinoma over a 10-year period (2007-2016) were reviewed. Five hundred forty-five histopathology reports were reviewed, and 71 cases were identified as potential cases of NIFTP. Forty-nine (69%) cases had been referred from external departments and the slides were not available for review. Of the remaining 22 (31% of 71) cases, 5 were reclassified as NIFTP. The 17 cases that were not reclassified as NIFTP required review of 114 of 356 slides (median 5.5 slides per case) was required to exclude NIFTP. For the 5 NIFTP cases, 58 slides were reviewed (median 12 slides per case). We found that review of the histology reports alone was adequate for exclusion in most cases, e.g. classic PTC or EVPTC cases with documented lymphovascular invasion or capsular invasion. As a single exclusion criterion is required for exclusion from reclassification as NIFTP, this can be achieved efficiently. Two of the five patients received radioactive iodine [RAI] as per standard treatment at time of diagnosis, on the basis of tumour size. None have recurrent or metastatic disease with mean follow-up of 5.8 years.

Brain complications of diabetes mellitus: a cross-sectional study of awareness among individuals with diabetes and the general population in Ireland.

AIMS: To identify awareness of potential brain complications of diabetes among individuals with diabetes and the public. METHODS: For this observational, cross-sectional survey study, we recruited consecutive adult attendees of a specialist diabetes clinic and two primary care practices. Primary care attendees represented members of the general population of Ireland. An interviewer-administered questionnaire was used to gather data on respondents' awareness of brain complications of diabetes and modifiable risk factors for dementia. Multivariable logistic regression was undertaken to identify variables independently associated with awareness. RESULTS: Respondents included a total of 502 adults: 250 in the diabetes group (37% women, mean age 63 ± 14 years, 88% with Type 2 diabetes) and 252 in the general population group (51% women, mean age 47 ± 17 years, 7% with Type 2 diabetes). The diabetes group had significantly greater awareness of diabetes complications, except for depression, compared with the general population group. In the group as a whole, respondent awareness of dementia (35%) and memory problems (47%) as potential complications of diabetes was poor compared with awareness of kidney (84%) and eye damage (84%). Respondents were 1.5 times more likely to identify that individuals can modify their risk of developing Type 2 diabetes than their risk of dementia. CONCLUSIONS: This study shows that there is poor awareness of brain complications of diabetes among individuals with diabetes and the general population in Ireland. The results suggest a need for expansion of public awareness campaigns and diabetes education programmes to promote awareness of the brain complications of diabetes and of the modifiable risk factors for dementia, as part of a life-course approach to dementia prevention.

Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry.

BACKGROUND AND OBJECTIVES: Medullary thyroid cancer consists of a spectrum of disease that ranges from extremely indolent tumors to aggressive types associated with a high mortality rate. The objective of our study is to evaluate the prognostic factors and outcomes of patients diagnosed with MTC in a homogenous population, and to examine patients diagnosed with MTC for mutations in the RET proto-oncogene from the same period. METHODS: A retrospective analysis of the National Cancer Registry in Ireland was undertaken, between 1998 and 2007. The Kaplan-Meier method was used to determine overall survival and factors predictive of outcome were determined by univariate and multivariate analysis by cox regression using Stata 13 software. MAIN FINDINGS: Forty-three patients were diagnosed with medullary thyroid cancer, 55.8 % were female and 44.2 % were male. A median age of 52 was found. The overall median survival was 6.32 years and the 1- and 5-year overall survival was 88.37 and 62.79 %, respectively, with 10-year survival calculated at 48.63 %. On univariate analysis age, stage and surgical intervention were statistically significant indicators of prognosis. T stage and age remained statistically significant indicators of prognosis on multivariate analysis. Two patients with no history of MEN syndromes or family history of medullary thyroid cancer had RET proto-onocogene mutations. CONCLUSIONS: Our patient cohort was substantially older and presented at an advanced T status than what is commonly seen in the literature. This may account for poor survival outcomes and the very low pick-up of RET mutations in sporadic medullary thyroid cancer.

Endocrine profiles in 693 elite athletes in the postcompetition setting.

OBJECTIVE: To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focusses attention on what may be considered as normal in this unusual group. DESIGN: Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a subset of 693. PARTICIPANTS: Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition. MEASUREMENTS: Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes. RESULTS: Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels, whereas 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men - sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones. CONCLUSIONS: Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.

Management of maple syrup urine disease in the peri-operative period.

Maple syrup urine disease (MSUD) has an incidence of 1:125,000 newborns in Ireland. Patients, when fasting, or in a catabolic state build up toxic metabolites leading to progressive neurological dysfunction. We describe the necessary peri-operative management of a patient with MSUD who developed symptomatic gallstones requiring a laparoscopic cholecystectomy.

A case of spontaneous hypoglycaemia and impaired glucose tolerance in the same patient.

We present a rare case of an insulin-like growth factor-2 (IGF-2)-secreting tumour of the thorax. This patient demonstrated the combination of fasting hypoglycaemia and impaired glucose tolerance on oral glucose tolerance testing, which has not been previously described in this condition. A review of the literature of IGF-2-secreting intrathoracic tumours is presented here.

Severe hypoglycaemia after long-acting octreotide in a patient with an unrecognized malignant insulinoma.

Insulinomas are the most common hormone-producing pancreatic neuroendocrine tumours (NETs), and patients usually present with symptoms secondary to hypoglycaemia. Octreotide has been widely used in the symptomatic treatment of patients with pancreatic NETs, including insulinomas. We describe a case of a patient with a metastatic NET, subsequently identified as a malignant insulinoma, who developed severe hypoglycaemia after treatment with long-acting octreotide.

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes.

CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.

High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes.

The anabolic actions of GH in GH-deficient adults and children are well documented. Replacement with GH in such individuals promotes protein synthesis and reduces irreversible loss of protein through oxidation. Although GH is known to be self-administered by athletes, its protein metabolic effects in this context are unknown. This study was designed to determine whether 4 wk of high dose recombinant human GH (r-hGH) administration altered whole body leucine kinetics in endurance-trained athletes at rest and during and after 30 min of exercise at 60% of maximal oxygen uptake. Eleven endurance-trained male athletes were studied, six randomized to receive r-hGH (0.067 mg/kg.d), and five to receive placebo. Whole body leucine turnover was measured at rest and during and after exercise, using a 5-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (an index of protein synthesis) were estimated. Under resting conditions, r-hGH administration increased rate of leucine appearance and nonoxidative leucine disposal, and reduced leucine oxidation (P < 0.01). This effect was apparent after 1 wk, and was accentuated after 4 wk, of r-hGH administration (P < 0.05). During and after exercise, GH attenuated the exercise-induced increase in leucine oxidation (P < 0.05). There were no changes observed in placebo-treated subjects compared with the baseline study. We conclude that GH administration to endurance-trained male athletes has a net anabolic effect on whole body protein metabolism at rest and during and after exercise.

Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) is known to be required for physical well-being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD). DESIGN: A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where nine continued with GH replacement. PATIENTS: GH-treated adults (10 men, 11 women), all with severe GHD (peak GH < 7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years). MEASUREMENTS: Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), the Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ). RESULTS: Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age-related levels (mean 26.6 +/- 13.2 nmol/l) to levels indicative of severe GHD (11.6 +/- 6.6 nmol/l) (P<0.001). Psychological symptoms of GH withdrawal, reported in interviews at end-point by placebo-treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end-point (chi2=11.25, P<0.01). Significant between-treatment-group differences in change scores were found for SF-36 General Health (P<0.01), W-BQ12 Energy (P<0.01) and HDQoL do physically (P<0.05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo-treated group at end-point relative to GH-treated patients. CONCLUSION: Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.

Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults.

GH is an important regulator of fat metabolism at rest, but it is not known whether it regulates fat metabolism during exercise. To determine whether physiologic concentrations of GH influence fat metabolism during exercise, we randomized 16 GH-deficient adults, receiving long-term (mean duration, 5 yr) GH replacement, to either continue GH (n = 8) or receive identical placebo (n = 8) for a 3-month period. Metabolic studies, at rest, during and following exhaustive exercise were carried out at baseline and at the end of the 3 months. The rate of appearance of glycerol (glycerol Ra, an index of lipolysis) and free fatty acids (FFA, FFA Ra) and the rate of disappearance of FFA (FFA Rd) in the plasma were measured using infusions of (2)H(5)-glycerol and 1-(13)C-palmitic acid. Changes in body composition were assessed using dual-energy x-ray absorptiometry scanning and anthropometric measurements. In the baseline studies, exercise resulted in an increase in plasma glycerol and FFA concentrations, glycerol Ra, FFA Ra, and FFA Rd (P < 0.001). Three months of GH withdrawal resulted in reductions in plasma glycerol and FFA, glycerol Ra, FFA Ra, and FFA Rd at rest (P < 0.05 vs. baseline) and during exercise (P < 0.05 vs. baseline and vs. GH treated). Lean body mass decreased after 3 months of GH withdrawal, but total body fat, trunk fat, waist circumference, and the sum of skinfold thicknesses increased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). Fasting insulin and homeostasis model assessment of insulin resistance decreased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). In summary, GH withdrawal for 3 months resulted in reductions in release of glycerol and FFA into the circulation and uptake of FFA into the tissues during intense exercise. These changes were accompanied by reduced lean body mass and increased total body and trunk fat. Further studies are required to determine whether reduced mobilization of fat during exercise contributes to reduced exercise capacity and increased body fat in GH-deficient adults.

The response of molecular isoforms of growth hormone to acute exercise in trained adult males.

Circulating GH consists of multiple molecular isoforms, all derived from the one gene in nonpregnant humans. To assess the effect of a potent stimulus to pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age, 26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise. Exercise consisted of continuous cycle ergometry at approximately 80% of predetermined maximal oxygen uptake for 20 min. Serum was assayed for total, pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All isoforms increased during, peaked at the end, and declined after exercise. At peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH and 20-kDa GH were significantly longer than those for all other isoforms. We conclude that 1) all molecular isoforms of GH measured increased with and peaked at the end of acute exercise, with 22-kDa GH constituting the major isoform in serum during exercise; and 2) the proportion of non-22-kDa isoforms increased after exercise due in part to slower disappearance rates of 20-kDa and perhaps other non-22-kDa GH isoforms. It remains to be determined whether the various biological actions of different GH isoforms impact on postexercise homeostasis.

Management strategies for an aging work force.

1. The demographic shift to an aging population has significant societal and cultural implications that carry over into the workplace. 2. The occupational and environmental health nurse needs to be aware of the risks associated with the aging process including physiological changes of aging, comorbidities and chronic diseases, and psychosocial factors as well as the impact those risks may have on work ability. 3. Health management strategies for an aging worker population include developing an older worker profile, creative job accommodations, and training programs. 4. The occupational and environmental health nursing scope of practice will require significant change for the profession to take a proactive approach to address this workplace transformation.

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.

Telecommuting: Occupational health considerations for employee health and safety.

1. Information technology has moved "work" out of a centralized location. Employees who telecommute pose significant challenges and considerations for the practice of occupational health nursing. 2. Employer and employee benefits associated with telecommuting are reportedly associated with high levels of job satisfaction. However, the occupational health and safety risks of this new work environment need to be fully assessed and understood. 3. The ergonomic controls to minimize the risk of repetitive motion injuries are the same for both office and home locations. Additional attention need to be paid to implementing risk controls for other physical hazards and psychosocial considerations, as well as personal safety and security issues. 4. The scope of occupational health nursing practice needs to remain dynamic, recognizing the impact new technologies have on the workplace, to continue to meet the needs of the changing workplace.