Are adverse outcome rates higher in multiple sclerosis patients after total hip arthroplasty?

Aims: This study compared multiple sclerosis (MS) patients who underwent primary total hip arthroplasty (THA) with a matched cohort. Specifically, we evaluated: 1) implant survivorship; 2) functional outcomes (modified Harris Hip Scores (mHHS), Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR), and modified Multiple Sclerosis Impact Scale (mMSIS) scores (with the MS cohort also evaluated based on the disease phenotype)); 3) physical therapy duration and return to function; 4) radiographic outcomes; and 5) complications. Patients and Methods: We reviewed our institution's database to identify MS patients who underwent THA between January 2008 and June 2016. A total of 34 MS patients (41 hips) were matched in a 1:2 ratio to a cohort of THA patients who did not have MS, based on age, body mass index (BMI), and Charlson/Deyo score. Patient records were reviewed for complications, and their functional outcomes and radiographs were reviewed at their most recent follow-up. Results: Compared with the matched cohort, MS patients had lower all-cause implant survivorship at eight years (91.5% (95% confidence interval (CI) 82.7 to 100) vs 98.7% (95% CI 96.2 to 100)) (p = 0.033), lower mHHS scores (66 vs 80, p < 0.001), and HOOS JR scores (79 vs 88, p = 0.009). Multiple sclerosis patients also required more physiotherapy (five weeks vs three weeks, p = 0.002) and took longer to return to baseline (seven weeks vs five weeks, p = 0.010) than the matched cohort. Furthermore, MS patients had more complications than the non-MS patients (six vs zero, p < 0.001). The worse outcomes of the MS group can potentially be explained by predisposition of these patients to mechanical complications and progression of their disease during the period of this study, as demonstrated by worsening of the mMSIS scores (2.9 vs 3.4; p = 0.008). Conclusion: MS patients had lower implant survivorship, lower functional outcome scores, and increased complication rates; in addition, MS patients took longer to return to their baseline functional level after THA. Cite this article: Bone Joint J 2018;100-B:875-81.

Structural analysis of a set of proteins resulting from a bacterial genomics project.

The targets of the Structural GenomiX (SGX) bacterial genomics project were proteins conserved in multiple prokaryotic organisms with no obvious sequence homolog in the Protein Data Bank of known structures. The outcome of this work was 80 structures, covering 60 unique sequences and 49 different genes. Experimental phase determination from proteins incorporating Se-Met was carried out for 45 structures with most of the remainder solved by molecular replacement using members of the experimentally phased set as search models. An automated tool was developed to deposit these structures in the Protein Data Bank, along with the associated X-ray diffraction data (including refined experimental phases) and experimentally confirmed sequences. BLAST comparisons of the SGX structures with structures that had appeared in the Protein Data Bank over the intervening 3.5 years since the SGX target list had been compiled identified homologs for 49 of the 60 unique sequences represented by the SGX structures. This result indicates that, for bacterial structures that are relatively easy to express, purify, and crystallize, the structural coverage of gene space is proceeding rapidly. More distant sequence-structure relationships between the SGX and PDB structures were investigated using PDB-BLAST and Combinatorial Extension (CE). Only one structure, SufD, has a truly unique topology compared to all folds in the PDB.

Outcome following acute myocardial infarction: are differences among physician specialties the result of quality of care or case mix?

BACKGROUND: Studies to determine whether care by cardiologists improves the survival of patients with acute myocardial infarction (MI) have produced conflicting results, and it is not known what accounts for differences in patient outcome by physician specialty. OBJECTIVES: To evaluate whether cardiologists provide more recommended therapies to elderly patients with acute MI and, if so, to determine whether variations in processes of care account for differences in patient outcome. DESIGN: Retrospective cohort study using medical chart data and administrative data files. SETTING: All nonfederal acute care hospitals in California. PATIENTS: A cohort of 7663 Medicare beneficiaries 65 years and older directly admitted to the hospital with a confirmed acute MI from April 1994 to July 1995 with complete data regarding potential contraindications to recommended therapies. MAIN OUTCOME MEASURES: Percentage of "good" and "ideal" candidates for a given acute MI therapy who actually received that therapy, percentage who received exercise stress testing or coronary angiography, percentage who underwent revascularization, and 1-year mortality, stratified by specialty of the attending physician. RESULTS: During hospitalization, good candidates for aspirin were more likely to receive aspirin if they were treated by cardiologists (87%) than by medical subspecialists (73%; P<.001), general internists (84%; P = .003), or family practitioners (81%; P<.001). Cardiologists were also more likely to treat good candidates with thrombolytic therapy (51%) than were medical subspecialists (29%; P<.001), general internists (40%; P<.001), or family practitioners (27%; P<.001). Patients of cardiologists were 2- to 4-fold more likely to undergo a revascularization procedure. Despite these differences in utilization, we found similar 30-day mortality rates across physician specialties. However, 1-year mortality rates were greater for patients treated by medical subspecialists (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.3), general internists (OR, 1.4; 95% CI, 1.3-1.6), and family practitioners (OR, 1.7; 95% CI, 1.4-1.9) than for those treated by cardiologists. Adjusting for differences in patient and hospital characteristics markedly reduced the ORs for those treated by medical subspecialists (OR, 1.2; 95% CI, 0.9-1.4), general internists (OR, 1.1; 95% CI, 1.0-1.3), and family practitioners (OR, 1.3; 95% CI, 1.1-1.6), whereas further adjustment for medication use and revascularization procedures had little effect. CONCLUSIONS: Differences in the use of recommended therapies by physician specialty are generally small and do not explain differences in patient outcome. In comparison, differences among patients treated by physicians of various specialties (case mix) have a large impact on patient outcome and may account for the residual survival advantage of patients treated by cardiologists. With the exception of the in-hospital use of aspirin, recommended MI therapies are markedly underused, regardless of the specialty of the physician.

Alternative approaches to public health surveillance of IDDM.

OBJECTIVE: To assess the appropriateness of national surveillance of IDDM. RESEARCH DESIGN AND METHODS: We reviewed the structure and function of national disease surveillance, the diverse goals of IDDM surveillance, and prior experience with IDDM as a reportable disease. RESULTS: Surveillance is the systematic and ongoing collection, analysis, interpretation, and dissemination of data linked to public health action. The potential goals of surveillance of IDDM are to understand the etiology and trends in incidence of IDDM, to measure the burden of IDDM and its complications, and to assess mortality. Problems associated with surveillance of IDDM include underreporting, delayed reporting, and lack of funding. CONCLUSIONS: To make IDDM a nationally reportable disease is neither warranted nor feasible at this time. Although surveillance is needed to understand diabetes better and for diabetes control, proposed initiatives, such as major expansions of IDDM reporting, should be developed to address specific questions, problems, and needs--still recognizing real-world issues of competing priorities and limited resources.

Survey of physician practice behaviors related to diabetes mellitus in the U.S. Physician adherence to consensus recommendations.

OBJECTIVE: To summarize the frequency of physician adherence to consensus recommendations for prevention of diabetic complications. RESEARCH DESIGN AND METHODS: Survey data from a nationwide stratified probability sample of primary-care physicians were analyzed. Adherence to recommendations were reported by physician specialty, age-group, and type of diabetes treated. RESULTS: Adherence was high for eye exams, blood pressure measurements, neurological and circulatory exams, and laboratory procedures using blood. Adherence was low for examination of the teeth and gums, examination of the feet, and laboratory procedures involving the collection of urine. Internists generally had the highest adherence rates and pediatricians the lowest. Reported adherence decreased with physician age. Adherence was higher for the management of individuals with IDDM than for those with NIDDM. CONCLUSIONS: Recommendations for the care of diabetic individuals need to be more widely implemented. Recommendations targeted specifically to pediatricians may be necessary.

Diabetes-associated mortality in Native Americans.

OBJECTIVE: To describe diabetes-associated mortality among Native Americans. RESEARCH DESIGN AND METHODS: In this population-based study, we analyzed diabetes-associated mortality data from the IHS and the NCHS. We also examined diabetes data from the 1986 NMFS. RESULTS: IHS area-specific diabetes mortality rates for 1984-1986 ranged from 10 to 93/100,000, compared with 15/100,000 for the total U.S. population. NCHS data for the same period listed diabetes as the underlying cause of 708 deaths among Native Americans and the contributory cause of 1252 deaths; 63% of the latter deaths were attributable to circulatory diseases. The 1986 NMFS demonstrated that Native American heritage is underreported by 65% on death certificates. Using deaths identified as Native American by NMFS, the age-adjusted mortality rate for diabetes as the underlying cause for Native Americans (96/100,000) was 4.3 times that for whites and two times that for blacks. Where diabetes was a contributory cause of death, the mortality rate for Native Americans (264/100,000) was 3.7 times that for whites and 2.4 times that for blacks. CONCLUSIONS: The excessive diabetes-associated mortality among Native Americans is consistent with other indicators of the magnitude of the diabetes problem in this population. Further epidemiological research and expanded diabetes control interventions are needed.

Trends in diabetes and diabetic complications, 1980-1987.

OBJECTIVE: Although diabetes is a major source of morbidity and mortality in the United States, only recently has a unified national surveillance system begun to monitor trends in diabetes and diabetic complications. RESEARCH DESIGN AND METHODS: We established a diabetes surveillance system using data for 1980-1987 from vital records, the National Health Interview Survey, the National Hospital Discharge Survey, and the Health Care Financing Administration's records to examine trends in the prevalence and incidence of diabetes, diabetes mortality, hospitalizations, and diabetic complications. RESULTS: From 1980 through 1987, the number of individuals known to have diabetes increased by 1 million--to 6.82 million. Age-standardized prevalence for diabetes increased 9% during this period, from 25.4 to 27.6/1000 U.S. residents (P = 0.03). The incidence of diabetes increased among women (P = 0.003), particularly among those greater than 65 yr old (P = 0.02). Age-standardized mortality rates (for diabetes as either an underlying or contributing cause) per 100,000 individuals with diabetes declined 12%, from 2350 to 2066. Annual mortality rates from stroke (as an underlying cause and diabetes as a contributing cause) and diabetic ketoacidosis declined 29% (P = 0.003) and 22% (P less than 0.001), respectively. During these 8 yr, hospitalization rates for major CVD and stroke (as the primary diagnoses and diabetes as a secondary diagnosis) increased 34% (P = 0.006) and 38% (P = 0.01), respectively. Also during this period, hospitalization rates increased 21% for diabetic ketoacidosis (P = 0.01) and 29% for lower-extremity amputations (P = 0.06). From 1982 through 1986, treatment for end-stage renal disease related to diabetes increased greater than 10% each year (P less than 0.001). The prevalence of diagnosed diabetes was nearly twice as high in blacks as in whites (P = 0.04). Blacks also had increased rates of lower-extremity amputation (P = 0.02), diabetic ketoacidosis (P less than 0.001), and end-stage renal disease (P = 0.01). CONCLUSIONS: Diabetes surveillance data will be useful in planning, targeting, and evaluating public health efforts designed to prevent and control diabetes and its complications.

Class-directed structure determination: foundation for a protein structure initiative.

The recent sequencing of many complete genomes, combined with the development of methods that allow rapid structure determination for many proteins, has changed the way in which protein structure determinations can be approached. One-by-one determinations of individual protein structures will soon be augmented by class-directed structure analyses in which a group of proteins is targeted and structures of representative members are determined and used to represent the entire group. Such a shift in approach would be the foundation for a broad protein structure initiative targeting classes of proteins important for biotechnology and for a fundamental understanding of protein function.

Blood-building foods in contemporary Chinese populations.

According to ancient Chinese medicine, "weak blood" is a yin condition that occurs during growth, pregnancy, the postpartum period, and old age. Treatment requires use of special foods that are "yang" in nature. This article investigated the use of such blood-building foods in seven contemporary Chinese populations throughout the world. Analysis of questionnaires from 379 respondents indicated that high-protein foods, such as pork liver and other meats, were recommended most often. Although these and other foods recommended were primarily yang, only 8.1% of respondents considered weak blood a "yin" condition. Comparison of 717 responses concerning foods that should be used to treat weak blood showed more similarities than differences between Chinese populations in different parts of the world. Strong adherence to cultural practices was also evident. Self-diagnosis and self-prescription are common modes of treating symptoms in the Chinese and other cultures. Knowledge of beneficial food-related health practices can enable practitioners to counsel their clients more effectively and to develop bilingual educational materials that incorporate familiar cultural practices.

Relationship of MTT reduction to stimulants of muscle metabolism.

MTT, a positively charged tetrazolium salt, is widely used as an indicator of cell viability and metabolism and has potential for histochemical identification of tissue regions of hypermetabolism. In the present study, MTT was infused in the constant-flow perfused rat hindlimb to assess the effect of various agents and particularly vasoconstrictors that increase muscle metabolism. Reduction of MTT to the insoluble formazan in muscles assessed at the end of experiments was linear over a 30 min period and production rates were greater in red fibre types than white fibre types. The vasoconstrictors, norepinephrine (100 nM) and angiotensin (10 nM) decreased MTT formazan production in all muscles but increased hindlimb oxygen uptake and lactate efflux. Veratridine, a Na(+) channel opener that increases hindlimb oxygen uptake and lactate efflux without increases in perfusion pressure, also decreased MTT formazan production. Membrane stabilizing doses (100 microM) of (+/-)-propranolol reversed the inhibitory effects of angiotensin and veratridine on MTT formazan production. Muscle contractions elicited by stimulation of the sciatic nerve, reversed the norepinephrine-mediated inhibitory effects on MTT formazan production, even though oxygen consumption and lactate efflux were further stimulated. Stimulation of hindlimb muscle oxygen uptake by pentachlorophenol, a mitochondrial uncoupler, was not associated with alterations in MTT formazan production. It is concluded that apart from muscle contractions MTT formazan production does not increase with increased muscle metabolism. Since the vasoconstrictors angiotensin and norepinephrine as well as veratridine activate Na(+) channels and the Na(+)/K(+) pump, energy required for Na(+) pumping may be required for MTT reduction. It is unlikely that vasoconstrictors that stimulate oxygen uptake do so by uncoupling respiration.

The disease-specific benefits and risks of physical activity and exercise.

Physical inactivity has been related to the occurrence of coronary heart disease, hypertension, diabetes mellitus, and osteoporosis. The literature was reviewed to determine what is and what is not known about the efficacy and safety of physical activity in each of these conditions. Although there is a transient increase in the risk of sudden cardiac death during vigorous activity, there is mounting evidence that habitual vigorous activity is associated with an overall reduced risk of coronary heart disease. It is unlikely that this association merely reflects the "selection" that results from sick persons who tend to be less active. Several studies suggest that physical activity may be related to the prevention and control of hypertension, diabetes mellitus, and osteoporosis. However, additional research is needed to make explicit the risks and benefits of physical activity in each of these conditions. Finally, future efforts should determine the type, intensity, frequency, and duration of activity required to maximize the benefits and minimize the hazards of physical activity. The public health and clinical significance of these questions requires that they be examined in the most rigorous manner feasible.

The Everglades Nutrient Removal Project test cells: STA optimization--status of the research at the north site.

The Everglades is an oligotrophic ecosystem that is being adversely impacted by hydrologic changes and nutrient-rich runoff generated from urban and agricultural sources. The Stormwater Treatment Area (STA) Optimization Research and Monitoring program is mandated by the 1994 Everglades Forever Act and will assist the South Florida Water Management District in developing operational strategies that maximize performance of emergent macrophyte STAs. The primary objective of this research is to examine how hydrologic conditions may influence STA performance. The study was conducted in 0.2 ha, shallow, fully lined test cells located within the perimeter of the Everglades Nutrient Removal Project. Experiments were designed to examine the effect of increased and decreased hydraulic loading rate (HLR) on wetland performance and to determine, if possible, the HLR at which STA treatment fails to reduce outflow total phosphorus concentration to the interim target of 50 microg-P/L. To date, two HLR experiments have been completed at the north site. Preliminary data indicated at all HLRs tested that particulate phosphorus and dissolved organic phosphorus ratios remained virtually unchanged from inflow to outflow. The dissolved organic and particulate compounds within these test cells are extremely recalcitrant, and are not easily assimilated within the system. High HLRs may not result in detention times long enough to mineralize these forms into easily assimilated inorganic compounds, resulting in mean TP concentrations greater than 50 microg-P/L.

Vascular and metabolic effects of methacholine in relation to insulin action in muscle.

AIMS/HYPOTHESIS: Methacholine (MC) is a nitric oxide vasodilator, but unlike other vasodilators, it potentiates insulin-mediated glucose uptake by muscle. The present study aimed to resolve whether this action was the result of a vascular effect of MC leading to increased muscle perfusion or a direct effect of MC on the myocytes. We hypothesise that vascular-mediated insulin-stimulated glucose uptake responses to MC occur at lower doses than direct myocyte MC-mediated increases in glucose uptake. METHODS: The vascular and metabolic effects of this vasodilator were examined in rats in vivo using a novel local infusion technique, and in the pump-perfused rat hindlimb under conditions of constant flow. RESULTS: Local infusion of low-dose MC (0.3 micromol/l) into the epigastric artery of one leg (test) in vivo markedly increased femoral blood flow and decreased vascular resistance, without effects in the contra-lateral leg. Capillary recruitment, but not glucose uptake, was increased in the test leg. All increases caused by MC were confined to the test leg and blocked by local infusion into the test leg of N-nitro-L-arginine methyl ester (L-NAME), but not by infusion of N-nitro-D-arginine methyl ester (D-NAME). In the constant-flow pump-perfused rat hindlimb, infusion of 0.6 micromol/l MC vasodilated the pre-constriction effected by 70 nmol/l noradrenaline or 300 nmol/l serotonin, and this was blocked by 10 micromol/l L-NAME. 2-Deoxyglucose in muscle was increased by 30 micromol/l MC (p<0.05), but was unaffected by 3 micromol/l MC. All increases in 2-deoxyglucose uptake by 30 micromol/l MC were blocked by 10 micromol/l L-NAME. CONCLUSIONS/INTERPRETATION: MC has dose-dependent effects both on the vasculature and on muscle metabolism. At low dose (0.3-3 micromol/l), MC is a potent vasodilator in muscle, both in vivo and in vitro, without metabolic effects; at higher doses (> or =30 micromol/l) MC has a direct metabolic effect leading to increased glucose uptake. Both the vascular and metabolic effects are sensitive to L-NAME. The low-dose enhancement of insulin action in vivo by MC, which has been reported previously, thus seems to be attributable to vascular effects.

Occult sternal metastasis identified by laminography in patients with chest pain.

Six patients with occult sternal metastasis presenting with chest pain, and four with sternal deformity associated with "arthritis" had undergone routine roentgenographic examinations, reported as "normal." Subsequent laminography of the sternum demonstrated lytic lesions confirmed by needle biopsy. Adenocarcinoma of the lung and breast were identified in two each of four patients; myeloma and kidney neoplasms were the primary source of malignancy in the remaining two patients. In widespread malignancy, metastasis to the skeletal chest wall is a well-recognized occurrence. Infrequently, it can be an isolated manifestation of an occult or recurrent malignancy, initially overlooked when routine roentgenograms are read as normal. Although sternal x-rays remain the most important means of diagnosis, in suspected cases of sternal metastasis laminography alone may initially reveal lytic lesions.

Stimulation and inhibition of resting muscle thermogenesis by vasoconstrictors in perfused rat hind limb.

Angiotensin (AII) and serotonin (5-HT) are both vasoconstrictors of the constant-flow perfused rat hind limb that have opposite effects on thermogenesis, possibly the result of differing effects on vascular flow distribution between nutritive and non-nutritive pathways. In the present study interaction between the two opposing agents was examined with the expectation that the combined presence would show additive effects on pressure and mutually neutralizing effects on thermogenesis. Thus doses of AII and 5-HT that gave similar, but opposite, quantitative effects on thermogenesis were infused alone, in combination one after the other, or in combination with the order reversed, and the effects on perfusion pressure (PP) and thermogenesis (oxygen uptake, VO2) were compared. AII (3 nM) alone increased PP by 15+/-1 mmHg (1 mmHg = 133.3 Pa) and VO2 by 3.1-/+0.2 micromol.h(-1).g(-1), whereas 5-HT (1 microM) alone increased PP by 75+/-6 mmHg and inhibited VO2 by 3.9+/-0.2 micromol.h(-1).g(-1). When added in combination, the outcome depended on the order of addition. Following AII, infusion of 5-HT further increased PP by 160+/-11 mmHg and decreased VO2 by 6.3+/-0.2 micromol.h(-1)g(-1). Following 5-HT, infusion of AII further increased PP by 28+/-4 mmHg and increased VO2 by only 1.8+/-0.3 micromol.h(-1).g(-1). The prior presence of 5-HT (1 microM) shifted the AII dose-response curves for VO2 and pressure to the right and left, respectively. The prior infusion of AII increased the dose-dependent response to 5-HT in terms of both the inhibition of VO2 and the increase in PP. At low doses of 5-HT (10(-8)-10(-7) M), but not alpha-methyl serotonin (alphaMT), there was a marked vasodilatation-associated inhibition of AII-mediated increase in VO2. Overall the data show that the combined effect of AII and 5-HT differed from the simple addition of each separately. Since the order of addition appears to be critical in terms of thermogenic outcome, it is concluded that each vasoconstrictor exerts a specific hemodynamic action to affect access of the other to vascular receptor sites. These findings are consistent with the previously reported effects of these vasoconstrictors on substrate and insulin access to muscle of the perfused rat hind limb.

Angiotensin II: endothelium-derived nitric oxide interaction in conscious rats.

In anesthetized rats, renal perfusion is largely regulated by a balance between the vasodilator influence of endothelium-derived nitric oxide (EDNO) and angiotensin II (AII)-mediated vasoconstriction. However, in conscious rats, which are characterized by lower PRA, the influence of AII is largely dissipated. To determine whether chronically increasing PRA enhances the interaction between AII and EDNO in regulating renal perfusion, radioactive microspheres were used to assess RBF in conscious sodium-depleted rats. PRA of control rats on a standard diet was 2.3 +/- 0.3 ng of AI/mL per hour compared with 16.8 +/- 1.5 ng of AI/mL per hour (P < 0.001) for rats on a sodium-restricted diet. In 12 rats on a standard diet, the inhibition of EDNO synthesis with L-Nw-nitroarginine methyl ester (L-NAME) increased blood pressure (BP) from 111 +/- 2 to 135 +/- 3 (P < 0.001) and decreased RBF by 47% (from 8.0 +/- 0.6 to 4.3 +/- 0.3 mL/min per gram kidney wt; P < 0.001). Renal vascular resistance (RVR) increased by 132% (from 14.9 +/- 1.2 to 34.7 +/- 3.3 resistance units (RU); P < 0.001). Pretreatment with Losartan, an AII receptor antagonist, did not modify the changes in BP, RBF, and RVR induced by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Vessels supplying septa and tendons as functional shunts in perfused rat hindlimb.

An assessment was made of the relationship between vasoconstrictor-mediated changes in metabolism and the apparent flow in putative nonnutritive vessels of muscle located on tendon. Surgically isolated rat hindlimbs were perfused at constant flow while monitoring perfusion pressure and venous pO2. In addition exposed tibial tendon vessels of the biceps femoris muscle of the perfused leg were positioned either under a surface fluorometer probe to monitor signal strength when pulses of fluorescein isothiocyanate dextran were infused or over the objective lens of an inverted microscope for photography when pulses of India ink were infused. Measurements were conducted under steady state with vehicle, norepinephrine, or serotonin infused. Norepinephrine increased perfusion pressure and oxygen uptake (VO2), but decreased fluorescence signal from the tendon vessels. Photomicroscopy confirmed that the vessels had generally decreased in diameter. Serotonin also increased perfusion pressure but decreased VO2 and increased fluorescence signal from the tendon vessels. Photomicroscopy confirmed that serotonin infusion had led to a marked increase in diameter of the vessels. It is concluded that a reciprocal relationship exists between resting muscle metabolism as controlled by vasoconstrictors and flow-through muscle tendon vessels.

Structural genomics in the post-genomics era - the shapes of things to come.

The overwhelming success of the current genomic sequencing efforts has spawned analogous efforts in the structural biology community. These new research efforts, termed 'structural genomics', seek to create and execute high-throughput structure determination that would allow scientists to obtain hundreds to thousands of relevant macromolecular structures in a fraction of the time required today. Groups in academia, national laboratories and industry are launching such efforts, each examining a different set of model organisms and each with a different research model. This review will present the current structural genomics efforts and the data that have been derived from these efforts to date. The utility of these projects to pharmaceutical drug discovery efforts will also be presented.