Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial.

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03). INTRODUCTION: To determine if teriparatide (20 µg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients. METHODS: This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test. RESULTS: The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months). CONCLUSION: In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

Prevalence of healthcare-associated infections and antimicrobial use among inpatients in a tertiary hospital in Fiji: a point prevalence survey.

BACKGROUND: Healthcare-associated infections (HAIs) and antimicrobial use (AMU) are important drivers of antimicrobial resistance, yet there is minimal data from the Pacific region. We sought to determine the point prevalence of HAIs and AMU at Fiji's largest hospital, the Colonial War Memorial Hospital (CWMH) in Suva. A secondary aim was to evaluate the performance of European Centre for Diseases Prevention and Control (ECDC) HAI criteria in a resource-limited setting. METHODS: We conducted a point prevalence survey of HAIs and AMU at CWMH in October 2019. Survey methodology was adapted from the ECDC protocol. To evaluate the suitability of ECDC HAI criteria in our setting, we augmented the survey to identify patients with a clinician diagnosis of a HAI where diagnostic testing criteria were not met. We also assessed infection prevention and control (IPC) infrastructure on each ward. RESULTS: We surveyed 343 patients, with median (interquartile range) age 30 years (16-53), predominantly admitted under obstetrics/gynaecology (94, 27.4%) or paediatrics (83, 24.2%). Thirty patients had one or more HAIs, a point prevalence of 8.7% (95% CI 6.0% to 12.3%). The most common HAIs were surgical site infections (n = 13), skin and soft tissue infections (7) and neonatal clinical sepsis (6). Two additional patients were identified with physician-diagnosed HAIs that failed to meet ECDC criteria due to insufficient investigations. 206 (60.1%) patients were receiving at least one antimicrobial. Of the 325 antimicrobial prescriptions, the most common agents were ampicillin (58/325, 17.8%), cloxacillin (55/325, 16.9%) and metronidazole (53/325, 16.3%). Use of broad-spectrum agents such as piperacillin/tazobactam (n = 6) and meropenem (1) was low. The majority of prescriptions for surgical prophylaxis were for more than 1 day (45/76, 59.2%). Although the number of handwashing basins throughout the hospital exceeded World Health Organization recommendations, availability of alcohol-based handrub was limited and most concentrated within high-risk wards. CONCLUSIONS: The prevalence of HAIs in Fiji was similar to neighbouring high-income countries, but may have been reduced by the high proportion of paediatric and obstetrics patients, or by lower rates of inpatient investigations. AMU was very high, with duration of surgical prophylaxis an important target for future antimicrobial stewardship initiatives.

Interventional therapy for carotid artery disease using angioplasty and stenting with embolic protection.

Carotid artery angioplasty with stenting (CAS) has emerged as a viable alternative to endarterectomy for the treatment of occlusive vascular disease. Advances in endovascular techniques and the improvement of specialized stents have served to rapidly close the gap with the traditional gold standard surgery. Furthermore, the development of cerebral embolic protection devices has reduced the occurrence of distal embolization of atheromatous material during such interventions and has reduced periprocedural stroke rates considerably. Continued improvements in distal embolic protection have further improved the risk profile of CAS, and increased operator experience with these interventional procedures has also been shown to reduce periprocedural complication rates. Outcomes may continue to improve as more providers gain experience with the evolving endovascular device technology, and several prospective clinical trials are currently investigating the efficacy of CAS with embolization protection versus endarterectomy in different cohorts. This review will survey the background and current literature covering angioplasty and stenting for occlusive disease in the carotid arteries and discuss the current methods employed to prevent distal emboli during intervention.

Metabolism and distribution of [2,3-(14)C]acrolein in lactating goats.

The metabolism and distribution of [2,3-(14)C]acrolein were studied in a lactating goat orally administered 0.82 mg/kg of body weight/day for 5 days. Milk, urine, feces, and expired air were collected. The goat was killed 12 h after the last dose, and edible tissues were collected. The nature of the radioactive residues was determined in milk and tissues. All of the identified metabolites were the result of the incorporation of acrolein into the normal, natural products of intermediary metabolism. There was evidence that the three-carbon unit of acrolein was incorporated intact into glucose, and subsequently lactose, and into glycerol. In the case of other natural products, the incorporation of radioactivity appeared to result from the metabolism of acrolein to smaller molecules followed by incorporation of these metabolites into the normal biosynthetic pathways.

Metabolism and distribution of [2,3-(14)C]acrolein in laying hens.

The metabolism and distribution of [2,3-(14)C]-acrolein were studied in 10 laying hens orally administered 1.09 mg/kg of body weight/day for 5 days. Eggs, excreta, and expired air were collected. The hens were killed 12-14 h after the last dose and edible tissues collected. The nature of radioactive residues was determined in tissues and eggs. All of the identified metabolites were the result of the incorporation of acrolein-derived radioactivity into normal natural products of intermediary metabolism in the hen except for 1,3-propanediol, which is a known degradation product of glycerol in bacteria.

An analysis of atrophy in the medial mammillary nucleus following hippocampal and fornix lesions in humans and nonhuman primates.

Lesions of the hippocampal formation or transections of the fornix are followed by shrinkage of the medial mammillary nucleus (MMN). We determined whether the shrinkage of this nucleus was due to loss and/or shrinkage of neurons in addition to the loss of neuropil. We examined the MMN in a patient (KB) with an infarct that led to marked atrophy of the left hippocampus and subiculum, leaving the right MMN intact. Unbiased, stereological measurement techniques were used to compare the total cell number and individual neuronal cross-sectional areas in both left and right MMN in this patient and in two control human brains. We also analyzed the MMN in four macaque monkeys that underwent experimental unilateral transections of the fornix. The volume of the MMN on the lesioned side in KB was 55% of the unlesioned side (2.8 mm(3) vs 5.1 mm(3)); the MMN in the monkey cases were reduced to 47-58% of the volume of the nonlesioned side. Neurons in the deafferented MMN of KB and of the monkey subjects were decreased in cross-sectional area (16-20%, P < 0.0001). There was a trend toward decreased cell numbers (11-15%) on the lesioned side in all cases. We have estimated that the loss in cell number and shrinkage of remaining cells contribute negligibly to the 45% reduction in MMN volume. Therefore, the loss of neuropil (dendrites and afferent and efferent axons) appears to be the major contributor to the change in MMN volume.

Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression.

Subunit dissociation and unfolding of macrophage NO synthase: relationship between enzyme structure, prosthetic group binding, and catalytic function.

Macrophage NO synthase is a homodimer of 130 kDa subunits. Each subunit contains an oxygenase domain that binds iron protoporphyrin IX (heme) and tetrahydrobiopterin (H4biopterin) and a reductase domain that binds FAD, FMN, and calmodulin (CaM) [Ghosh & Stuehr (1995) Biochemistry 34, 801-807]. We have studied the dissociation and unfolding reactions of dimeric iNOS in urea to learn how enzyme structure relates to catalysis and prosthetic group binding. The iNOS dimer dissociated between 0 and 2.5 M urea, and the subunits partially unfolded at 2.5 M urea and above. Dimer dissociation was accompanied by loss of NO synthesis activity and release of bound H4biopterin from the protein. However, the dissociated subunits maintained their cytochrome c and ferricyanide reductase activities and retained near stoichiometric quantities of bound heme. The subunit unfolding transition was accompanied by loss of reductase activities and partial loss of bound heme but retention of bound flavins and CaM. The heme iron in the dissociated subunits remained coordinated through axial cysteine thiolate ligation. Kinetic analysis of dimer dissociation showed that loss of NO synthesis correlated with a loss of heme Soret absorbance at 398 nm and an appearance of absorbance bands at 377 and 460 nm, which were attributed to DTT coordination to the sixth position of the heme iron to form a mixed bisthiolate complex. Subunits could reassociate into a dimer when incubated with L-arginine and H4biopterin. Dimer formation correlated with proportional recoveries of NO synthesis and heme Soret absorbance at 398 nm. Thus, dimeric iNOS undergoes separate dissociation and unfolding transitions in urea, and each transition is accompanied by a loss of a specific catalytic function.(ABSTRACT TRUNCATED AT 250 WORDS)

A rapid method for cosmid cloning.

We present a method for genomic library construction using cosmid vectors. With a combination of backfilling with Klenow enzyme and a cosmid vector with two cos sites, a DNA bank in excess of 500,000 clones can be made from 10 micrograms of genomic DNA. The method is more rapid than conventional protocols because size fractionation of target DNA is not necessary. A further advantage is that libraries can be made from relatively small amounts of genomic DNA.

DNA variants of alpha-1-antitrypsin in rheumatoid arthritis with and without pulmonary complications.

Restriction fragment length polymorphisms (RFLPs) of alpha-1-antitrypsin were studied in 99 subjects with rheumatoid arthritis alone, 21 subjects with rheumatoid arthritis and pulmonary fibrosis, 26 subjects with rheumatoid arthritis and bronchiectasis, and 86 controls. No associations with either rheumatoid arthritis itself or with the associated pulmonary disorders were noted in this U.K. Caucasoid population.

The effect of education on foodservice manager job satisfaction.

We conducted a study to determine whether educational background (field of study and level of education) was related to the job satisfaction of foodservice managers. The Index of Organizational Reactions Questionnaire was used to measure specific components of job satisfaction based on a five-point Likert-style scale (1 = low satisfaction, 3 = moderate satisfaction, and 5 = high satisfaction). Questionnaires were mailed to the entire population of 256 foodservice managers employed in college and university dining facilities of a regional division of a major foodservice company in the northeastern United States. Names, titles, positions, and addresses of the managers were obtained from the company's human resources department. Analysis of data was done through computation of the point-biserial correlation coefficient and the rank order correlation coefficient. Managers who responded to the questionnaire (74.6%) indicated moderate overall job satisfaction (mean = 3.42 on a 5-point scale). Of the respondents, 44% had an educational background in foodservice; these respondents had lower overall job satisfaction than did those having no education/training in foodservice. Both groups were most satisfied with the job components of supervision, type of work, and relationship with coworkers. Both groups were least satisfied with pay and benefits, company identification, and amount of work. A significant (p less than .01) positive relationship was found between educational field of study and job satisfaction, and a significant (p less than .001) negative relationship was found between educational level (i.e., degree[s] earned) and job satisfaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical times for families with a chronically ill child.

Parents identified difficult times in caring for their chronically ill children. A model describing these critical times was developed through an analysis of parent interviews. Predicting these critical times enables the health care team to optimize and maximize the effectiveness of their interventions.