Biomedical subjects
P Ross
Publications and source records attributed to P Ross.
Ergonomic hazards in the workplace: assessment and prevention.
1. Ergonomic hazards impact employers and workers and their families. Poor workplace design, awkward body mechanics or postures, repetitive movements, and other ergonomic hazards induce or contribute to a staggering number of cumulative trauma disorders. 2. Cumulative trauma disorders (CTD) affect hands, wrists, elbows, arms, shoulders, the lower back, and the cervical spine area. Structures involved include tendons, muscles, bones, nerves, and blood vessels. One can plan strategies for abatement by learning to recognize the hazards that contribute to CTD. 3. OSHA has published the Ergonomic Program Management Guidelines. OSHA has also given Advance Notice of Proposed Rulemaking for an Ergonomic Standard that will affect all industries. 4. A company wide ergonomic assessment should be developed, followed by a well written ergonomic plan. Ergonomic abatement will decrease the costs associated with CTD and ultimately impact the corporate "bottom line."
Career grade posts in NHS trusts.
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Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy.
PURPOSE: To determine the effect of long-term intermittent cyclic etidronate treatment on spinal bone density and vertebral fracture rates. PATIENTS AND METHODS: Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study; it was extended to a third year of blinded treatment followed by open-label treatment: 357 patients continued treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days, etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for the remainder of each 91-day treatment cycle. During Year 4, open-label intermittent cyclic etidronate therapy (without preceding phosphate) was administered to all patients. Spinal bone density and vertebral fracture rates were the main outcome measures. RESULTS: During Year 3, etidronate therapy maintained the significant increases in spinal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as compared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively; p < 0.05). After 1 year of open-label treatment, patients previously treated with etidronate maintained bone mass, and vertebral fracture rates in all groups were lower than in any other study period. There were no apparent serious adverse effects. CONCLUSIONS: Three years of intermittent cyclic etidronate therapy produced significant increases in spinal and hip bone density, with a significant reduction in vertebral fracture rates in patients at higher fracture risk. Maintenance of bone mass and low fracture rate were observed when etidronate was continued for an additional year.
The significance and prevention of air emboli with the total artificial heart.
Embolism remains a significant complication of the total artificial heart (TAH). The ineffectual deairing of the TAH can allow embolization of the retained air. The standard needle aspiration of TAH air (Group A) was compared with a new protocol (Group B) that included standard needle TAH aspiration plus simultaneous pumping of the TAH against an occluded ascending aorta and main pulmonary artery with vacuum applied to a needle in the proximal aorta and pulmonary artery. There were 4 calves in each group. There was no premortem evidence of systemic or pulmonary emboli. Both groups of animals were electively terminated less than 2 weeks postoperatively Postoperative mean aortic and pulmonary artery pressures were recorded for each animal. Animals in Group B had a significant decline in pulmonary artery pressures (43 +/- 12 vs. 33 +/- 8 mm Hg) 1 h after TAH implantation when compared with Group A. All other aortic and pulmonary artery pressure differences between Groups A and B were not statistically significant within 24 h of the operation. Group A animals had a 75% incidence, and Group B animals had 100% incidence of TAH thrombus. This very small thrombus was found exclusively at the inflow valve-TAH housing interface. Evaluation of the kidneys postmortem was used to identify embolic injury. All animals in Group A had evidence of acute, hemorrhagic injury, but none of the Group B animals had similar injury. Half of the animals in each group had small, fibrotic chronic renal cortical injury, which did not develop during TAH implantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Partial characterization of galactosyltransferase in human seminal plasma and its distribution in the human epididymis.
Galactosyltransferase activity has been partially characterized in human seminal plasma. Km values of 130 mumol l-1 for UDP-galactose and 2.25 mmol l-1 for N-acetylglucosamine were calculated and the enzyme was found to be dependent on temperature and manganese and present as a highly active component of human seminal plasma. Galactosyltransferase was inhibited by nucleotides, glycosylated nucleotides, bovine and human alpha-lactalbumin but not by monosaccharides. Radiation inactivation studies revealed that the biologically active unit of seminal plasma galactosyltransferase has a molecular mass of 45 kDa. Although the majority of galactosyltransferase activity found in seminal plasma is probably of prostatic origin, we report for the first time that it is also present in human epididymal intraluminal fluid. Low activity was detected in the proximal caput region but activity increased to maximum values in the adjacent downstream segment, the intermediate caput region. Specific activity was relatively constant albeit at a lower value in the following epididymal segments and vas deferens. The significance of the epididymal and seminal plasma galactosyltransferase activities is unknown, but the enzyme could be implicated in glycosylation events that are known to be important in gamete interaction.
Preferential osteopenia in women with osteoporotic fractures.
One-hundred thirty-six women with spontaneous vertebral crush fractures had bone density measurements by photon absorptiometry. Their absolute and relative extent of osteopenia were expressed as Z scores with respect to values from normal white women. Absolute Z scores were used to express the mean bone mass of women with crush fractures vis-a-vis normal women at peak bone mass; relative Z scores were used to express the same means vis-a-vis age-matched controls. The skeletal sites measured included the distal radius, lumbar spine, and three sites on the femur (neck, Ward's triangle, and trochanter). The absolute deficit for the five sites ranged from -1.66 to -2.60. The relative deficit was close to 1 SD for all sites. A discriminant analysis revealed that the spine and femur were predictive for vertebral crush fractures but the radius was not. Comparison with a previously reported hip-fracture population (n = 31) showed that the low bone density of the spine separated the two fracture groups best. We propose the following: (a) vertebral-fracture patients have extensive generalized osteoporosis including the hip with a preferential deficit in the spine and (b) hip-fracture patients have generalized osteoporosis with preferential osteopenia of the hip and do not have a greater mineral deficit in the spine or radius than age-matched normal women. It may be that if a single site is to be selected for screening for spine and hip fractures, the greatest value would be in measurement of the femur, although ideally the skeletal site of interest would be measured. Prospective studies are needed to confirm the utility of measurements at the spine and hip in prediction of future fractures.
Cadmium concentrations in the kidneys of Western Australian pigs.
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Hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency: a prevalence study in Quebec (Canada).
Fifty-eight cases of hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency were collected from both laboratories that have performed the assay since 1972 and from attending physicians in the province of Quebec. Using the postal addresses of the probands, a prevalence map was constructed according to the administrative regions of the province of Quebec. The prevalence was found to be higher in eastern Quebec (1/81,838) than in western Quebec (1/139,086). Fifty probands were of French Canadian origin whereas the remaining 6 were recent immigrants.
Treatment of cryptosporidiosis with paromomycin. A report of five cases.
Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.
Polypeptide composition of bacterial cyclic diguanylic acid-dependent cellulose synthase and the occurrence of immunologically crossreacting proteins in higher plants.
To comprehend the catalytic and regulatory mechanism of the cyclic diguanylic acid (c-di-GMP)-dependent cellulose synthase of Acetobacter xylinum and its relatedness to similar enzymes in other organisms, the structure of this enzyme was analyzed at the polypeptide level. The enzyme, purified 350-fold by enzyme-product entrapment, contains three major peptides (90, 67, and 54 kDa), which, based on direct photoaffinity and immunochemical labeling and amino acid sequence analysis, are constituents of the native cellulose synthase. Labeling of purified synthase with either [32P]c-di-GMP or [alpha-32P]UDP-glucose indicates that activator- and substrate-specific binding sites are most closely associated with the 67- and 54-kDa peptides, respectively, whereas marginal photolabeling is detected in the 90-kDa peptide. However, antibodies raised against a protein derived from the cellulose synthase structural gene (bcsB) specifically label all three peptides. Further, the N-terminal amino acid sequences determined for the 90- and 67-kDa peptides share a high degree of homology with the amino acid sequence deduced from the gene. We suggest that the structurally related 67- and 54-kDa peptides are fragments proteolytically derived from the 90-kDa peptide encoded by bcsB. The anti-cellulose synthase antibodies crossreact with a similar set of peptides derived from other cellulose-producing microorganisms and plants such as Agrobacterium tumefaciens, Rhizobium leguminosarum, mung bean, peas, barley, and cotton. The occurrence of such cellulose synthase-like structures in plant species suggests that a common enzymatic mechanism for cellulose biogenesis is employed throughout nature.
Biochemical short-term changes produced by hormonal replacement therapy.
Seventy-one white women within 6 months to 6 years postmenopause were randomly assigned to three treatment groups: (a) placebo, (b) calcium, (c) cyclic estrogen-progestin plus calcium. Calcium was given as calcium carbonate with meals to attain an intake of 1,700 mg daily in the latter two groups. All women received 400 IU of vitamin D daily. Samples were obtained at baseline and after 2 months therapy. The hormonal treatment group had a decline in serum calcium, osteocalcin and urinary hydroxyproline and an increase in levels of calcitonin, parathyroid hormone and calcitriol. The increase in the latter two measurements could have resulted from the drop in serum calcium, it is also possible that the increase in calcitonin levels was a result of calcium supplementation. Although all these changes were statistically significant for the estrogen treatment group when considered alone, analysis of variance including the 3 groups demonstrated significance for the estrogen group for the parameters of skeletal metabolism but not for the changes in the calciotrophic hormones. There was an increase in serum calcium (p = 0.05) in the calcium augmentation group. It would be of interest to determine the effects of higher intakes of calcium in both the calcium and the estrogen treatment groups and to further explore differences in effects on bone remodeling between the two treatment approaches as well as the possibility of a additive effects. Early effects of estrogen replacement reduce bone remodeling whereas calcium supplementation to 1,700 mg per day of Ca CO3 did not appear to affect the parameters of bone remodeling.
Relationship of menopause to skeletal and muscle mass.
Cross-sectional and longitudinal changes in body composition with age were examined in white women to determine the relationship of body cell mass to menopause and of body fat to bone mass. There was statistical evidence for a curvilinear component to loss of total body potassium with negligible rates of loss before menopause. Longitudinal measurements also indicated a relationship between the proximity to menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against bone loss.
Rheumatoid arthritis: fish oil? Or snake oil?
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Cellulose biosynthesis and function in bacteria.
The current model of cellulose biogenesis in plants, as well as bacteria, holds that the membranous cellulose synthase complex polymerizes glucose moieties from UDP-Glc into beta-1,4-glucan chains which give rise to rigid crystalline fibrils upon extrusion at the outer surface of the cell. The distinct arrangement and degree of association of the polymerizing enzyme units presumably govern extracellular chain assembly in addition to the pattern and width of cellulose fibril deposition. Most evident for Acetobacter xylinum, polymerization and assembly appear to be tightly coupled. To date, only bacteria have been effectively studied at the biochemical and genetic levels. In A. xylinum, the cellulose synthase, composed of at least two structurally similar but functionally distinct subunits, is subject to a multicomponent regulatory system. Regulation is based on the novel nucleotide cyclic diguanylic acid, a positive allosteric effector, and the regulatory enzymes maintaining its intracellular turnover: diguanylate cyclase and Ca2(+)-sensitive bis-(3',5')-cyclic diguanylic acid (c-di-GMP) phosphodiesterase. Four genes have been isolated from A. xylinum which constitute the operon for cellulose synthesis. The second gene encodes the catalytic subunit of cellulose synthase; the functions of the other three gene products are still unknown. Exclusively an extracellular product, bacterial cellulose appears to fulfill diverse biological roles within the natural habitat, conferring mechanical, chemical, and physiological protection in A. xylinum and Sarcina ventriculi or facilitating cell adhesion during symbiotic or infectious interactions in Rhizobium and Agrobacterium species. A. xylinum is proving to be most amenable for industrial purposes, allowing the unique features of bacterial cellulose to be exploited for novel product applications.
Clarification of the role of CT scan in the acute evaluation of blunt abdominal trauma.
We reviewed 100 patients sustaining blunt trauma whose initial evaluation included an abdominal computed tomographic scan (CT) to assess the role of this modality in managing these patients. Indications for CT scan were suspicion of abdominal injury based on mechanism of injury (46), tenderness (22), falling hematocrit (9), hematuria (5), pain (4), and hyperamylasemia (1). Thirty-four patients had abdominal injury, and four scans identified non-traumatic pathology; 66 patients had no evidence of abdominal injury. There were no additional abdominal injuries detected during the hospitalizations. Mechanism of injury was the only indication for CT scan in 20 patients, none of whom had evidence of abdominal injury. CT scan charges for these 20 patients accounted for 5.5% of the total hospital bill ($204,070). Hospital costs would have been reduced by $11,270 if these patients had been followed clinically. Fifteen patients with soft tissue contusions and normal CT scans were hospitalized less than 72 hours. Room and other hospital charges accounted for 38.5% of the hospital bill; these are costs that would have been saved if these patients had been discharged from the emergency service. Several conclusions can be made from this study. First, abdominal CT scan is a sensitive test for abdominal injury. Secondly, patients without objective signs of abdominal injury whose other injuries warrant admission allowing further observation should be followed clinically and do not need the additional expense of abdominal CT scan. Finally, mechanism of injury alone is not an indication for CT scan.
Effect of thiazide on rates of bone mineral loss: a longitudinal study.
OBJECTIVE: To determine the effect of thiazide diuretic drugs on rates of bone mineral loss. DESIGN: Longitudinal, observational study with a mean follow up of five years. SETTING: Hawaii Osteoporosis Center, Honolulu. SUBJECTS: 1017 Japanese-American men born between 1900 and 1920, of whom 378 were treated for hypertension (study group) and 639 did not have hypertension (control group). INTERVENTION: Thiazide diuretics were taken by 325 men for a mean of 11.9 years; 53 men took antihypertensive drugs other than thiazides. MAIN OUTCOME MEASURE: Rate of bone loss estimated from serial photon absorptiometric scanning at three skeletal sites (calcaneus, distal radius, and proximal radius). RESULTS: Rates of bone loss at all three sites were significantly reduced among thiazide users when compared with controls. The reductions in loss rate ranged from 28.8% (p = 0.02) (distal radius) to 49.2% (p = 0.0005) (calcaneus) relative to the controls. At all three sites the men taking other antihypertensive drugs had faster loss rates (22.6-43.1%) than those of the controls but the difference was significant only for the distal radius. CONCLUSION: Thiazide diuretics slow the rate of bone loss in elderly men.
The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives.
An unusual compound, cyclic-bis(3'----5') diguanylic acid (c-di-GMP or cGpGp), is involved in the regulation of cellulose synthesis in the bacterium Acetobacter xylinum. This cyclic dinucleotide acts as an allosteric, positive effector of cellulose synthase activity in vitro (Ka = 0.31 microM) and is inactivated via degradation by a Ca2(+)-sensitive phosphodiesterase, PDE-A (Km = 0.25 microM). A series of 13 analogs cyclic dimer and trimer nucleotides were synthesized, employing a phosphotriester approach, and tested for the ability to mimick c-di-GMP as activators of cellulose synthase and as substrates for PDE-A. Seven of the synthetic compounds stimulate cellulose synthase activity and all of these activators undergo the Ca2(+)-inhibited degradation reaction. The order of affinities for synthase activators is cGpGp approximately cdGpGp approximately cGp(S)Gp (S-diastereomer) greater than cIpGp greater than cdGpdGp greater than cXpGp greater than cIpIp greater than cGp(S)Gp (R-diastereomer). Three cyclic dinucleotides of negligible affinity for either enzyme are cApAp, cUpUp, and cCpCp. This same order of affinities essentially pertains to the analogs as inhibitors of PDE-A activity, but at least one cyclic dinucleotide, cXpXp, which does not bind to cellulose synthase, is also a substrate for the degradation reaction, demonstrating that although the two enzymes share a similar, high degree of specificity for c-di-GMP, their cyclic dinucleotide binding sites are not identical. Phosphodiester bonds of activators in which an exocyclic oxygen is replaced with an atom of sulfur (cGp(S)Gp isomers) resist the action of PDE-A, and such derivatives may be prototypes for synthetic non-hydrolyzable c-di-GMP analogs.