Oxidative stress and its control: a pathogenetic role in inflammatory joint disease.
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Animals↗
Biomedical subjects
R J Ward
Publications and source records attributed to R J Ward.
A complementary role for thallium-201 scintigraphy with mammography in the diagnosis of breast cancer.
Physical examination and mammography are currently the only proven and reliable methods of early detection of breast cancer. Although both procedures are highly sensitive, their limited specificity often requires surgical biopsy in order to differentiate between malignant and benign lesions. The purpose of this prospective study is to investigate the diagnostic specificity of thallium imaging for breast cancer and to determine its efficacy as a complement to mammography. Two groups were studied: Group A: Patients found to have breast abnormalities and scheduled for biopsy or surgery and Group B: Patients who were suspected to have a recurrence of cancer after mastectomies or lumpectomies. In Group A, thallium scans of 32 breasts in 30 patients were performed prior to biopsy or surgery, yielding pathological diagnoses of 31 breasts in 29 patients. Results for Group A included seven true-positive thallium scans, twenty-two true-negative scans, two false-negative scans, and one false-positive scan. In Group B, seven patients were scanned to evaluate subcutaneous nodules for breast cancer following mastectomy or lumpectomy. Results for Group B included five true-positive scans, one true-negative scan, one false-negative scan and no false-positive scans. Thallium breast scanning was shown to have high specificity for cancer (specificity 96% and sensitivity 80%), suggesting that this technique should be evaluated in additional patient studies to determine its role in clinical situations.
Adult↗
The evaluation and management of known or suspected stones of the common bile duct in the era of minimal access surgery.
Laparoscopic cholecystectomy (LC) has rapidly become the procedure of choice for symptomatic cholelithiasis. The perioperative diagnosis and modern treatment of suspected stones of the common bile duct (CBD) remains controversial. A database of 573 patients undergoing LC was compiled during an 11 month period. Sixty-seven patients (47 females, 20 males) (13 percent) were suspected of having CBD stones based upon clinical, laboratory and roentgenographic evidence. Fifty-two patients underwent endoscopic retrograde cholangiopancreatography (ER-CP) (45 preoperative and seven postoperative). Seventeen patients were studied with intraoperative cholangiogram (IOC). The indications for cholangiography (either ERCP or IOC) included pancreatitis (group 1), clinical history suggestive of CBD stones, but normal preoperative liver function tests (LFT) (group 2), cholangitis (group 3), grossly abnormal LFT (group 4) and dilated CBD (greater than 7 millimeters on sonogram) (group 5). The incidence of CBD stones was three of 14 (21 percent) in group 1, six of 20 (30 percent) in group 2, two of three (67 percent) in group 3, 16 of 26 (62 percent) in group 4 and two of four (50 percent) in group 5. Overall, 29 patients (23 females and six males) had stones retrieved from the CBD. Of the 52 ERCP, 20 endoscopic sphincterotomies were performed for documented CBD stones. Of the group that had pre-LC ERCP, three (6 percent) ultimately required an open procedure. There were three instances of post-ERCP pancreatitis (6 percent) and ERCP was not able to opacify or clear the CBD in four instances. Seven patients had postoperative ERCP with successful retrieval of retained CBD stones (100 percent). Of the 17 IOC, eight were positive--two patients underwent laparoscopic clearance of the CBD and six required conversion to an open procedure. There were no deaths or extensive complications. Total and direct bilirubin, alkaline phosphatase and serum glutamic pyruvic transaminase were independently related to the presence of a CBD stone, while demographic data, past medical history, preoperative symptoms, leukocyte count, vital signs, amylase, serum glutamic-oxalacetic transaminase nuclear scintigraphic visualization of the duodenum or size of CBD on sonography, were not. No patient with biliary pancreatitis had CBD stones without abnormalities in the LFT or the preoperative sonogram. ERCP is a useful technique to clear the CBD pre-LC. However, ERCP in patients with biliary pancreatitis, but otherwise normal preoperative tests, has a low yield. In this group of patients, IOC is an appropriate alternative to pre-LC ERCP.
Adult↗
Mathematical modelling of ethanol metabolism in normal subjects and chronic alcohol misusers.
The time course of ethanol disappearance from the blood has been examined in normal males and females and in alcohol misusers. Blood alcohol estimations were made over a period of 3 hr, following an oral dose of ethanol (0.8 g/kg body weight) administered in the form of whisky. Attempts were made to fit the data to zero order, first order and mixed zero + first order kinetics. In the majority (75%) of normal females the blood ethanol concentrations was still increasing at 30 min. This was only seen in 50% of normal males and in 50% of non-dependent alcohol misusers, but not in dependent alcohol misusers. In all of the normal females the disappearance of ethanol could be adequately described by zero order kinetics. However, in the normal male group only 20% could be described by zero order kinetics, 10% fitted first order kinetics and the remainder required a mixed model of zero + first order. The rate constant for the zero order component of the control male group was identical to zero order rate constant obtained for the female control group. In the female alcohol misuser group, 40% of the curves could not be described by zero order kinetics and fitted best to a mixed model. The zero order component of the entire group was significantly increased (by 35%) compared to that obtained for the female control group. In the male dependent and non-dependent alcohol misuser groups, all blood alcohol concentration curves fitted best to mixed zero and first order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Iron metabolism--new perspectives in view.
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Animals↗
Chemical and structural characterisation of iron cores of haemosiderins isolated from different sources.
The elemental content of the iron cores of haemosiderins isolated from animal and human tissues has been determined to ascertain whether changes in composition are correlated with structural differences previously identified in these mineralisation products. Significant differences were observed in the elemental composition of haemosiderins isolated from patients subjected to desferrioxamine-chelation therapy compared to patients who had been venesected. The P/Fe molar ratio was considerably higher in haemosiderin isolated from treated primary haemochromatosis (0.83), compared to untreated primary haemochromatosis (0.10) and treated secondary haemochromatosis (0.25), and this could account for the amorphous nature of these iron cores. The levels of M/Fe (M = Ca, Cu, Zn) were reduced in the haemosiderins derived from treated secondary haemochromatosis patients, possibly due to the chelation of these ions by desferrioxamine therapy. In an experimentally iron-loaded rat, receiving either desferrioxamine or 1,2-diethyl-3-hydroxypyrid-4-one, selective decreases in these three elements were also observed after two weeks of desferrioxamine therapy. Such changes may be important determinants in the modification of biomineralisation of the iron cores.
Animals↗
Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat.
The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.
Animals↗
Alpha-tocopherol levels in brain are not altered in Parkinson's disease.
alpha-Tocopherol (vitamin E) levels in normal brain were lower in the cerebellum than in the cerebral cortex or basal ganglia. There was no difference in alpha-tocopherol levels in the cerebellum, basal ganglia, or cerebral cortex between control subjects and patients with Parkinson's disease.
Aged↗
Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease.
1. We have determined the antioxidant status of synovial fluid and serum of patients with inflammatory joint disease in terms of the biologically active lipid-soluble antioxidant, alpha-tocopherol. Synovial fluid concentrations of alpha-tocopherol were significantly lower relative to those of paired serum samples (P < 0.001). Serum levels of alpha-tocopherol in these patients did not differ significantly from those in control serum. 2. Lower concentrations of cholesterol, triacylglycerol and low-density lipoprotein were also observed in patients' synovial fluid compared with matched serum samples. However, multiple regression analysis of the data indicated that there remained a significant depletion of alpha-tocopherol, which was largely independent of these co-variables, in inflammatory synovial fluid. These findings are consistent with the consumption of alpha-tocopherol within the inflamed joint via its role in terminating the process of lipid peroxidation. 3. Nuclear magnetic resonance spectroscopic analysis of matched inflammatory synovial fluid and serum confirmed lower concentrations of triacylglycerol in synovial fluid together with evidence of a shortened mean triacylglycerol chain length. The latter metabolic difference suggests an increased utilization of triacylglycerols for energy within the inflamed joint.
Arthritis↗
Imidazole dipeptides in experimental alcohol-induced myopathy.
Rats were chronically fed a nutritionally complete liquid diet containing 35% of total calories as either ethanol, or (for the controls) an isocaloric amount of glucose. After 6 weeks of treatment, the feeding regime induced skeletal muscle myopathy as characterised by reductions in muscle weight and RNA content. Ethanol preferentially affected the metabolically glycolytic plantaris (Type II fibre-predominant) muscle of the rat, compared with the metabolically oxidative soleus (Type I fibre-predominant). The changes in the plantaris were associated with increases in the concentration (mumol per g wet weight) of anserine (18%) and carnosine (50%). No significant changes were seen for the concentrations of either anserine or carnosine in the soleus muscle. The total contents (mumol per muscle) of carnosine and anserine in the plantaris were not significantly altered by ethanol treatment, though a significant decrease in anserine content (30%) occurred in the soleus. It is concluded that reductions in imidazole dipeptide content, considered to be antioxidants and/or intracellular buffering agents, are not mediating factors in the development of chronic experimental myopathy.
Animals↗
The antioxidant status of patients with either alcohol-induced liver damage or myopathy.
The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants alpha-tocopherol and beta-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of beta-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, beta-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas alpha-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both alpha-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers.
Adult↗
Iron K-edge absorption spectroscopic investigations of the cores of ferritin and haemosiderins.
The extended X-ray absorption fine structure (EXAFS) associated with the iron K-edge has been measured and interpreted for ferritin and haemosiderin extracted from horse spleen, and haemosiderin extracted from the livers of humans with treated primary haemochromatosis, and from the spleens of humans with treated secondary haemochromatosis. For ferritin, the data are consistent with, on average, each iron atom being in an environment comprised of approx. six oxygen atoms at 1.93 +/- 0.02 A, approx. 1.5 iron atoms at 2.95 +/- 0.02 A and approx. 1.1 iron atoms at 3.39 +/- 0.02 A, with a further shell of oxygens at approx. 3.6 A. Iron in horse spleen haemosiderin is in an essentially identical local environment to that in horse spleen ferritin. In contrast, the EXAFS data for primary haemochromatosis haemosiderin indicate that the iron-oxide core is amorphous; only a single shell of approx. six oxygen atoms at approx. 1.94 +/- 0.02 A being apparent. Secondary haemochromatosis haemosiderin shows an ordered structure with approx. 1.4 iron atoms at both 2.97 +/- 0.02 and 3.34 +/- 0.02 A. This arrangement of iron atoms is similar to that in horse spleen haemosiderin, but the first oxygen shell is split with approx. 2.9 atoms at 1.90 +/- 0.02 A and approx. 2.7 at 2.03 +/- 0.02 A, indicative of substantial structural differences between secondary haemochromatosis haemosiderin and horse spleen haemosiderin.
Animals↗
Biochemical and biophysical investigations of the ferrocene-iron-loaded rat. An animal model of primary haemochromatosis.
Male Wistar rats fed with ferrocene had high hepatic iron loading (7.24 +/- 1.97 mg Fe/g tissue) after 6 weeks, principally located in lysosomes, which was comparable to the levels and distribution determined in human haemochromatosis. The two iron-storage proteins, ferritin and haemosiderin were isolated from the livers of the ferrocene-loaded rats and their iron cores were investigated by Mössbauer spectroscopy and inductively coupled plasma-emission spectrometry. Ferrihydrite was the predominant form of iron present in both ferritin and haemosiderin, while haemosiderin contained higher amounts of phosphorus, magnesium, calcium and barium, then either normal or ferrocene-loaded ferritin. Free-radical-mediated damage in the iron-loaded livers was inferred by the significant depletion of alpha-tocopherol in both the livers and subcellular hepatic lysosomal fraction, which inversely correlated with the increasing iron content (r = -0.61; P less than 0.05) and was associated with increased fragility of the lysosomal membranes.
Animals↗
The 'topping-up' effect: differences between low- and non-alcoholic lager on blood ethanol.
The peak blood alcohol levels attained in male and female subjects after consumption of 3 pints of regular lager (4.2%) over a 30 min period was 73.5 +/- 6.9 mg% in males and 113 +/- 17 mg% in females. Peak values occurred at 60 and 90 min post-ingestion in males and females, respectively. Consumption of 3 pints of low-alcohol lager gave a maximum blood alcohol level of 13 mg% while there was no measurable blood alcohol content after three pints of non-alcohol lager. 'Topping-up' with a non-alcohol lager after 2 pints of regular lager leads to significantly lower blood alcohol levels when compared with 'topping-up' with low-alcohol lager over a comparable time in males but not in females.
Alcohol Drinking↗
A comparison of obstetric and nonobstetric anesthesia malpractice claims.
Malpractice claims filed against anesthesiologists for care involving obstetric (OB) anesthesia (n = 190) were taken from the American Society of Anesthesiologists' Closed Claims Database and compared to claims not involving OB cases (n = 1351). The most common complications in the OB claims were (percentage of all OB claims): maternal death (22%), newborn brain damage (20%), and headache (12%). In contrast, the most common complications in the nonobstetric (non-OB) group were (percentage of all non-OB claims): death (39%), nerve damage (16%), and brain damage (13%). The group of OB claims contained a proportionately greater number of minor injuries, such as headache, backache, pain during anesthesia, and emotional injury (32%) compared to the non-OB claims (4%). Complications due to aspiration and convulsions were more common among the OB cases. The standard of care was judged to have been met in 46% of OB and 39% of non-OB claims. This difference is not statistically significant. Claims involving general anesthesia were more frequently associated with severe injuries and resulted in higher payments than did claims involving regional anesthesia. Payments were made in a similar proportion of OB and non-OB claims (53 and 59%, respectively). For cases in which payments were made, the median payment for OB claims was significantly greater ($203,000) than for non-OB claims ($85,000; P less than or equal to 0.05).
Adult↗
Laparoscopic Stamm gastrostomy with gastropexy.
Recent technologic advances in video equipment and instruments have enabled therapeutic gastrointestinal operations to be performed laparoscopically. Using these advances and laparoscopic techniques, we have performed a Stamm gastrostomy with gastropexy by using the laparoscope in a single patient. The technique, indication, and considerations are discussed herein.
Abdominal Muscles↗
Method for forming two-dimensional paracrystals of biological filaments on lipid monolayers.
A method is described for electron microscopic observation of two-dimensional paracrystals on unsupported lipid monolayers. The method uses a hydrophobic holey C-coated grid placed on a monolayer made positively charged by the inclusion of stearylamine (SA) and has been used to align scallop thin filaments and reconstituted actin/tropomyosin filaments to form paracrystals. The use of unsupported monolayers allows the paracrystals to be viewed in either negative stain or with cryoelectron microscopy. Those paracrystals in frozen hydrated specimens have better order than those with negative stain. It was found that varying the lipid composition between the less fluid distearolyphosphotidylcholine/SA and the more fluid egg yolk phosphotidylcholine/SA alters the size and order of the paracrystals, the more fluid system having smaller, more ordered paracrystalline domains. The advantage of the technique for studying actin/thin filaments is the ability to form large two-dimensional paracrystals under physiological conditions of [Mg2+] and pH.
Crystallization↗
Measuring interrater reliability among multiple raters: an example of methods for nominal data.
This paper reviews and critiques various approaches to the measurement of reliability among multiple raters in the case of nominal data. We consider measurement of the overall reliability of a group of raters (using kappa-like statistics) as well as the reliability of individual raters with respect to a group. We introduce modifications of previously published estimators appropriate for measurement of reliability in the case of stratified sampling frames and we interpret these measures in view of standard errors computed using the jackknife. Analyses of a set of 48 anaesthesia case histories in which 42 anaesthesiologists independently rated the appropriateness of care on a nominal scale serve as an example.
Reproducibility of Results↗