Evaluation of functionality-mobility in patients with skeletal dysplasias. Application of the STEMS tool ("everyday symptoms and mobility screening tool for skeletal dysplasias").

Individuals with differing forms of skeletal dysplasias (SD) frequently report impaired mobility and symptoms. With the objetive to evaluate mobility and associated symptoms in people with SD at an Argentinian pediatric hospital, using an Argentinian version of the Screening Tool for Everyday Mobility and Symptoms (STEMS), a simple questionnaire that allows clinicians to quickly identify the presence of symptoms associated with mobility in people with SD, while considering different environmental settings and the use of assistive devices, an analytical study of a consecutive sample of patients older than 5 years with SD and their affected relatives was carried out.Diagnosis, comorbidities, socioenvironmental, therapeutic, auxological and mobility variables were recorded. The presence and intensity of symptoms was noted through use of both the STEMS and validated scales. Descriptive, association and correlation analyzes were performed. One hundred and nineteen individuals with SD were enrolled in the study and divided into groups: Osteogenesis Imperfecta (OI, n = 55), Achondroplasia (ACH, n = 36) and Other SD resulting in disproportionate short stature (n = 28). Mobility assistive devices were almost exclusively used by individuals with OI. They were more frequently used by individuals with overweight and obesity, more severe form of the disease and in the outdoor settings. Two thirds (66.4%) of the individuals assessed in this study reported pain, 87.4% reported fatigue, and 58.8% reported both pain and fatigue. The intensity of symptoms was similar between groups and correlated with age and auxological variables. The STEMS was clear, easy and quick to use for identifying presence of pain and fatigue in this population group. The STEMS proved to be a simple and useful tool for evaluating functional mobility and associated symptoms in our population of individuals with SD.

Feeding jejunostomy in upper gastrointestinal resections: a UK-wide survey.

INTRODUCTION: The usage of a feeding jejunostomy has been a well-established practice in maintaining nutrition in patients undergoing resections for upper gastrointestinal cancer. As surgical technique has evolved, together with the adoption of enhanced recovery after surgery pathways, the routine insertion of feeding jejunostomy tubes appears to be changing. MATERIALS AND METHODS: A survey was constructed using Google Forms. The link was distributed to consultant upper gastrointestinal surgeons via the Association of Upper Gastrointestinal Surgeons' membership database. Results were collated and analysed using Microsoft Excel. RESULTS: A total of 55 responses were received from 28 units across the UK; 27 respondents (49.1%) no longer routinely use feeding jejunostomy in upper gastrointestinal resections, oesophagectomy or gastrectomy. The most common primary feeding modality used by these respondents was oral diet 17 (65.4%), with total parenteral nutrition (19.2%) and nasojejunal (11.5%) routes also being used. Respondents who used feeding jejunostomies inserted them primarily for oesophagectomy (n = 27; 96.4%), with fewer surgeons using them in extended total gastrectomy (n = 12; 42.9%) and total gastrectomy (n = 11; 39.3%). Of the total, 20 surgeons (71.4%) would insert the jejunostomy using an open approach, with 19 (67.9%) employing a Witzel tunnel. Eleven respondents (39.3%) would continue feeding via the jejunostomy after discharge. Some 24 responders thought that feeding jejunostomies did not facilitate the enhanced recovery after surgery pathway (strongly and slightly disagree), whereas 17 considered that they did (strongly and slightly agree); 13 responders did not have strong views either way. CONCLUSIONS: There is a split in current practice regarding the usage of feeding jejunostomies. There is also a division of opinion on the role of feeding jejunostomy in enhanced recovery after surgery.

High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation.

We demonstrate simultaneous control of both the phase and amplitude of light using a conjugate gradient minimisation-based hologram calculation technique and a single phase-only spatial light modulator (SLM). A cost function, which incorporates the inner product of the light field with a chosen target field within a defined measure region, is efficiently minimised to create high fidelity patterns in the Fourier plane of the SLM. A fidelity of F = 0.999997 is achieved for a pattern resembling an LG10 mode with a calculated light-usage efficiency of 41.5%. Possible applications of our method in optical trapping and ultracold atoms are presented and we show uncorrected experimental realisation of our patterns with F = 0.97 and 7.8% light efficiency.

Construction of an inducible system for the analysis of essential genes in Yersinia pestis.

Yersinia pestis, a Gram negative bacterium, causes bubonic and pneumonic plague. Emerging antibiotic resistance in clinical isolates is driving a need to develop novel antibiotics to treat infection by this transmissible and highly virulent pathogen. Proteins required for viability, so called essential genes, are attractive potential therapeutic targets, however, confirmation of essentiality is problematic. For the first time, we report the development of a system that allows the rapid determination of Y. pestis gene essentiality through mutagenesis and inducible expression of a plasmid borne copy of the target gene. Using this approach, we have confirmed the uridine monophosphate kinase PyrH as an essential protein in Y. pestis. This methodology and the tools we have developed will allow the confirmation of other putative essential genes in this dangerous pathogen, and facilitate the identification of novel targets for antimicrobial development.

RelA regulates virulence and intracellular survival of Francisella novicida.

Analysis of the genome of Francisella tularensis has revealed few regulatory systems, and how the organism adapts to conditions in different niches is poorly understood. The stringent response is a global stress response mediated by (p)ppGpp. The enzyme RelA has been shown to be involved in generation of this signal molecule in a range of bacterial species. We investigated the effect of inactivation of the relA gene in Francisella by generating a mutant in Francisella novicida. Under amino acid starvation conditions, the relA mutant was defective for (p)ppGpp production. Characterization showed the mutant to grow similarly to the wild-type, except that it entered stationary phase later than wild-type cultures, resulting in higher cell yields. The relA mutant showed increased biofilm formation, which may be linked to the delay in entering stationary phase, which in turn would result in higher cell numbers present in the biofilm and reduced resistance to in vitro stress. The mutant was attenuated in the J774A macrophage cell line and was shown to be attenuated in the mouse model of tularaemia, but was able to induce a protective immune response. Therefore, (p)ppGpp appears to be an important intracellular signal, integral to the pathogenesis of F. novicida.

Concurrent validity of the Functional Independence Measure for Children (WeeFIM) and the Pediatric Evaluation of Disabilities Inventory in children with developmental disabilities and acquired brain injuries.

The Functional Independence Measure for Children (WeeFIM) and the Pediatric Evaluation of Disability Inventory (PEDI) are the most commonly used measures of functional performance in children. The purpose of this study was to determine the concurrent validity of the instruments when used with children with developmental disabilities and acquired brain injury. The subjects were 41 children, age 1.3 to 9.5 years, who were receiving inpatient or outpatient services at a pediatric rehabilitation unit in Brisbane, Australia. Spearman correlation coefficients between the two tests were greater than 0.88 for self care, transportation/locomotion, and communication/social function. The high correlations indicate that the two tests measure similar constructs. Choosing between the tests depends on situational requirements and depth of information required.

The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation.

OBJECTIVE: To assess the validity of the Anti Cancer Council of Victoria food frequency questionnaire (ACCVFFQ) relative to seven-day weighed food records (WFRs) in 63 women of child-bearing age. METHOD: 63 women completed WFRs to assess iron intake as part of a study on iron deficiency. These women also completed the ACCVFFQ. Nutrient intakes were computed independently for the WFRs and FFQs. Intakes were compared as group means, by correlation and by quintile classification, adjusting for day-to-day variation in intakes, and for energy intake. Individual differences in results were also examined. RESULTS: The strongest associations between WFR and FFQ results were energy-adjusted, log-transformed and adjusted for day-to-day variability in intake. Correlation coefficients ranged from 0.28 for vitamin A to 0.78 for carbohydrate. Mean intakes from the WFRs and FFQs were within +/- 20% for 21 of 27 nutrients. Poor agreement between FFQs and WFRs for retinol intake was due to the inclusion of liver in two WFRs, an item which is not included in the FFQ. CONCLUSION: The ACCVFFQ performs as well as other FFQs for which validation data are available. The relatively poor measurement of retinol is consistent with other data, and with the limited number of foods in which this nutrient is abundant. IMPLICATIONS: The availability of an optically scannable valid instrument for assessing dietary intake will facilitate epidemiological studies of diet and disease, an area of current research priority.

Isolation and characterization of a unique sulfated ganglioside, sulfated GM1a, from rat kidney.

A novel class of sulfoglycosphingolipid, a sulfate analog of ganglioside, was isolated from mammals for the first time. This sulfated ganglioside was purified from rat kidney by column chromatographies on anion exchangers and silica beads. One-dimensional 1H NMR, compositional and permethylation analyses showed that this glycolipid has a Gg4Cer core with 1 mol each of sulfate ester and N- glycolylneuraminic acid (NeuGc) at C-3 of galactose. The major ceramide consisted of nonhydroxy fatty acids (24:0 and 22:0) and 4-hydroxysphinganine (t18:0), deduced from the compositional analysis and negative liquid secondary ion mass spectrometry (LSIMS). Mild acid hydrolysis and solvolysis produced compounds which correspond to Gg4Cer IV3-sulfate (SM1b) and II3NeuGcalpha-Gg4Cer (GM1a (NeuGc)), respectively. The abundant ions characteristic for sulfated mono- and disaccharides in high-energy collision-induced dissociation (CID) spectra were consistent with the structure at the non-reducing terminus, HSO3 -O- Hex -O- HexNAc- rather than the alternative structure, NeuGc -O- Hex -O- HexNAc-. The two-dimensional 1H NMR further evidenced the presence of a 3 -O- sulfated galactose in the molecule. From these results the complete structure was proposed to be HSO3-3Galbeta-3GalNAcbeta-4(NeuGcalpha-3)Galb eta-4Glcbeta-1Cer (II3NeuGcalpha-Gg4Cer IV3-sulfate).

Do postmenopausal women with NIDDM have a reduced capacity to deposit and conserve lower-body fat?

OBJECTIVE: To compare regional body fat distribution and sex hormone status of postmenopausal women with NIDDM with those of age- and BMI-matched normoglycemic women. RESEARCH DESIGN AND METHODS: The regional body fat distribution and sex hormone status of 42 postmenopausal women with NIDDM were compared with those of 42 normoglycemic women matched for age and BMI, who served as control subjects. Body composition was measured by dual-energy X-ray absorptiometry, and sex hormone-binding globulin (SHBG) and testosterone were measured in serum. RESULTS: Although the levels of total body fat were similar between the two groups, the women with NIDDM had significantly less lower-body fat (LBF) (P < 0.01) than the control subjects matched for age and BMI. This pattern of fat deposition in women with NIDDM was accompanied by an androgenic hormone profile, with decreased SHBG concentration and an increased free androgen index (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: A reduced capacity to deposit and/or conserve LBF may be an independent factor associated with (or may be a marker of) the metabolic manifestations of the insulin resistance syndrome in women with NIDDM. The possibility that the smaller relative accumulation of LBF is a consequence of the androgenic hormonal profile should be investigated in future studies.

Diet, nutrition and prostate cancer.

Although much has been written, little is known about the causes of prostate cancer. Variations between populations in the incidence of invasive cancers, together with changes in the incidence of invasive cancers in migrants, have pointed to environmental (lifestyle) factors that might be amenable to intervention. Conversely, there is a lack of international variation in the prevalence of microscopic tumours, so the essential question is: what causes only some of the common microscopic tumours to become aggressive? Dietary factors hold the most promise in this regard and have been the subject of recent reviews. The strongest and most consistent effects are positive associations with animal products such as red meats, eggs and dairy foods, and possibly by implication, fat. Evidence of a protective effect of fruit and vegetables is weak and inconsistent, as is the relationship with vitamin A and carotenoids, such as beta-carotene. There are some interesting leads. Lycopene, the carotenoid found in tomatoes, has been reported to be protective; alpha-tocopherol supplementation has shown a protective effect in one intervention study; and vitamin D has been shown to be protective in a prospective study. Interest is also growing in phytoestrogens and the extent to which dietary manipulation with these and other phytochemicals might influence prostate cancer by modifying male sex hormone levels or actions. There is limited evidence of associations with obesity. It is not known whether these are related to a particular dietary pattern or to possible physiological effects on the male's hormonal milieu. Associations with lean body mass are likely to be related to the action of androgens during growth and development. Dietary and nutritional effects on prostate cancer do not appear to be strong, but they may be subtle and attenuated by measurement error. To explore these aspects further will require large prospective studies that include improved (repeated) dietary measurements and also blood sampling, so that genetic polymorphisms can be adequately investigated. Such studies are underway.

Evaluation of the autonomic cardiovascular response in Arnold-Chiari deformities and cough syncope syndrome.

OBJECTIVE: To study the autonomic control of heart rate in patients with Arnold-Chiari deformity types I and II who exhibit the signs and symptoms of cough syncope syndrome. DESIGN: Prospective, clinical descriptive study. SETTING: University clinical research center. PATIENTS: Nine patients with Arnold-Chiari deformity and cough syncope syndrome. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Changes in heart rate, blood pressure, and electrocardiograms for power spectral analysis of heart rate variability were studied in the supine and standing positions, preoperatively (n = 9) and postoperatively (n = 5). RESULTS: Preoperatively, 8 (89%) of 9 patients increased their heart rate after postural change from supine to standing (mean +/- SD delta = 13 +/- 13 beats per minute [bpm]). Postoperatively, 4 (80%) of the 5 patients exhibited a greater increase in standing heart rate (mean delta = 19 +/- 16 bpm) compared with preoperative values. Changes in systolic, diastolic, and mean blood pressure with postural change were variable. Preoperatively, all patients exhibited abnormal control of heart rate in response to postural change. Three patients (33%) showed an abnormal decrease in low-frequency heart rate power (mean delta = -27 +/- 35 bpm2); the remaining 6 (67%) demonstrated an abnormal increase in high-frequency heart rate power (mean delta = 25 +/- 41 bpm2). All patients were clinically asymptomatic at 2 months after surgery. A normal spectral response to postural change was demonstrated in heart rate power in all 5 patients who were reevaluated postoperatively, with an increase in low-frequency power (mean delta = 33 +/- 21 bpm2) and a decrease in high-frequency power (mean delta = -21 +/- 23 bpm2). CONCLUSIONS: Patients with cervicomedullary anatomic abnormalities caused by Arnold-Chiari deformities may exhibit abnormal autonomic control of heart rate, and the autonomic control of their heart rate returns to a normal pattern after surgical palliation in conjunction with resolution of clinical symptoms.

Blood pressure in the Australian- and Italian-born: a Melbourne suburb revisited after 20 years.

The aim of this study was to investigate changes in the average blood pressure of Australian-born and Italian-born men and women after a 20-year interval, in the same location, the Melbourne suburb of Brunswick, located about five km north of the centre of the city. Data pertaining to blood pressure and its control were obtained from all Australian- and Italian-born residents of Brunswick enrolled in the Melbourne Collaborative Cohort Study between 1990 and 1994. Comparisons were made with published data from a random household survey in Brunswick in 1972. Within the age group 40 to 59 years (in contrast to the earlier study) average blood pressure was significantly higher in Italian-born men and women relative to the Australian-born. Between 1972 and 1990-1994, significant reductions in average systolic and diastolic blood pressure occurred in Australian-born women aged 40 to 59 years. Average systolic and diastolic blood pressures also fell in Australian-born men, although the reduction in systolic blood pressure for those aged 50 to 59 was not statistically significant. Average systolic blood pressure increased in Italian-born men and women. However, the increase was statistically significant only for men aged 50 to 59 years. Average diastolic blood pressure increased in Italian-born men aged 50 to 59 and fell in Italian-born women of the same age. The observed changes in blood pressure could not be attributed directly to changes in the diagnosis and treatment of hypertension, or to changes in the prevalence of overweight and obesity.

Structural characterization of a novel mono-sulfated gangliotriaosylceramide containing a 3-O-sulfated N-acetylgalactosamine from rat kidney.

A novel mono-sulfated glycosphingolipid based on the gangliotriaose core structure was isolated from rat kidney. The isolation procedure involved extraction of lipids with chloroform/methanol, mild alkaline methanolysis, column chromatographies with anion exchangers and silica beads. The structure was characterized by compositional analysis, FTIR spectroscopy, methylation analysis, 1H-NMR spectroscopy and negative-ion liquid secondary ion mass spectrometry (LSMIS) using the intact glycolipid and its desulfation product. The two dimensional chemical shift correlated spectroscopy provided information on the sugar sequence as well as anomeric configurations, and indicated the presence of a 3-O-sulfated N-acetylgalactosamine within the molecule. Negative-ion LSIMS with high- and low-energy collision-induced dissociation defined the sugar sequence and ceramide composition, confirming the presence of a sulfated N-acetylgalactosamine at the non-reducing terminus. From these results, the complete structure was proposed to be HSO3-3GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer (Gg3Cer III3-sulfate, SM2b).

Revision total joint arthroplasty: does medicare reimbursement justify time spent?

In 1991, five different total joint replacement surgeons performed 337 primary total knee replacements and 250 primary total hip replacements. They revised 25 total knee replacements and 73 total hip replacements. The average length of stay was 6.6 days for the primary total knee arthroplasty and 7.5 days for knee revisions. For total hip replacement, average stay was 5.9 days for primary surgery and 6 days for revisions. The operative time required for each of the five surgeons to complete a total knee replacement increased 55%, 3%, 38%, 72% and 38%; whereas for the total hip replacement, time increased 87%, 77%, 84% and 58%. Overall, there was a 41% increase in operating time for revision total knee replacements and a 77% increase for revision total hip replacement. Allowable charges by Medicare in 1993 for a primary knee and hip replacement were $1,298 and $1,363, respectively. Revision total knee replacement increased 24.3% ($1,613) and revision total hip replacement increased 30.8% ($1,782) in the state of Indiana. These figures do not encourage those surgeons who are capable of doing total joint replacements to revise other surgeons' problems.

Structural analysis of mono- and bis-sulfated glycosphingolipids by negative liquid secondary ion mass spectrometry with high- and low-energy collision-induced dissociation.

Several underivatized mono- and bis-sulfated glycosphingolipids having gangliotriaose or gangliotetraose core structure were analyzed by negative liquid secondary ion mass spectrometry (LSIMS) with high- and low-energy collision-induced dissociation (CID). In the normal negative LSIMS spectra, each mono-sulfated glycolipid gave abundant [M - H]- ions and each bis-sulfated glycolipid gave abundant [M + Na - 2H]- ions as well as the hydrogen sulfate anion [OSO3H]-. In high-energy CID spectra of the deprotonated molecule, only ions containing a sulfate ester were clearly observed. When a sulfate was present on the non-reducing terminal saccharide residue, a series of ions corresponding to sulfated mono- to tetra-saccharides, resulting from sequential cleavage of glycosidic bonds, were observed. If the sulfate was attached to an internal hexose of the sugar chain, the product ions corresponding to the non-sulfated, non-reducing terminal residue were absent. In contrast, the low-energy CID resulted in extremely simple spectra that contained only one or two major product ions characteristic of each sulfated glycolipid. These results provided clear information on the overall sugar and ceramide compositions, and allowed saccharide structures differing in location and number of sulfate esters to be distinguished.

Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation.

The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.