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Biomedical subjects

M J Dennis

Publications and source records attributed to M J Dennis.

At least 19 recordsLinked to original sources

Scrapie infection alters the distribution of plasma metabolites in diseased Cheviot sheep indicating a change in energy metabolism.

Nuclear magnetic resonance (NMR) spectroscopy has been used to profile the metabolic status of plasma from; sheep showing clinical signs of scrapie, those known to be infected with scrapie but yet to show clinical signs, and control animals. The NMR measurements have shown that energy metabolism in scrapie infected animals is altered before the onset of clinical symptoms. These metabolic changes may provide the foundation for a pre-clinical diagnostic test for scrapie in sheep.

Animals↗

Comparative evaluation of the performance of two commercial kits for the detection of central nervous system tissue in meat.

The ScheBo Brainostic test, which detects neuron-specific enolase by Western blotting, and the r-Biopharm Ridascreen Risk Material ELISA test, which detects the presence of glial fibrillary acidic protein, were evaluated using meats containing spinal cord and brain central nervous system (CNS) tissue from ovine and bovine species. The meats were pork, cooked pork sausage, raw minced lamb and cooked minced lamb. Spiking of the CNS tissue ranged from 0.01 to 5%. No false-positives were observed with either test using the manufacturers' analytical protocols. The presence or absence of CNS tissue was correctly determined in 20 of 20 samples using the ScheBo Brainostic test and 18 of 20 samples using the Ridascreen tests. When results were placed in categories according to quantity of CNS tissue detected, 19 of 20 samples were classified correctly using the Brainostic test and 14 of 20 samples using the Ridascreen test. Both kits were considered appropriate for reporting the presence of 1% or more CNS tissue in meat products, but the ScheBo Brainostic test was more consistent at detecting the presence of CNS tissues below the 1% level. Overall, the format of the Ridascreen test was technically easier to use, and the data simpler to interpret.

Animals↗

Survey of stable sulfur isotope ratios (34S/32S) of sulfite and sulfate in foods.

A study was conducted to determine the natural abundance sulfur isotope ratios in foods containing sulphite preservatives. This involved determining (1) the accuracy and repeatability of sulfur isotope ratios measured using an elemental analyser (EA) coupled to an isotope ratio mass spectrometer (IRMS); and (2) the isotope ratios of 21 samples of commercially available S(IV) oxo-anion compounds, nine samples of S(VI) sulfate salts and the isotope ratios of the sulfate obtained by modified Monier-Williams distillation of SO(2) from 33 retail foods containing sulfite preservatives. The sulfur isotope ratio data for SO(2) recovered from foodstuffs showed a large spread of results, which suggested that the SO(2) derived from sulfite preservatives does not have a distinctive sulfur signature ratio. The range of results (3.1-52.1) overlapped with that found for a range of commercially available sulfite and sulfate reagents commonly used to preserve food (sulfites 2.5-13.7, sulfates 10.0-16.9). Whilst the variability in isotope ratios originated from the food samples themselves, evidence from the analysis of SO(2) gas suggested that isotope fractionation during dissolution, reaction and recovery was also a confounding factor.

Barium Sulfate↗

Radiation exposure with use of the inverted-c-arm technique in upper-extremity surgery.

BACKGROUND: Intraoperative fluoroscopy is commonly used in surgical procedures on upper extremities. We compared radiation exposure from two possible positions of the mobile digital fluoroscopy unit (c-arm): (1) the standard technique, with the x-ray tube down (near the floor) and the image intensifier at the top of the c-arm, and (2) the inverted position, in which the image intensifier is used as a table and the x-ray tube is up. METHODS: A commercially available c-arm was used to irradiate a phantom hand in one of three configurations. In the first, the phantom hand was placed on an armboard equidistant from the x-ray tube and the image intensifier with the beam directed upward. In the second, the c-arm was inverted with the beam directed downward and the image intensifier used as a table. The third configuration was identical to the second except that a magnified image was used. Radiation exposure was measured at four locations corresponding to the approximate position of the surgeon's head, chest, and groin and the patient's hand. RESULTS: The amount of radiation exposure to both the surgeon and the patient was significantly less when the c-arm was used in the inverted position (p < 0.0001). The dose rate to the patient's hand was reduced by 59%. The radiation exposure to the surgeon's head, body, and groin with the inverted-c-arm technique was 67%, 45%, and 15% of the measured doses with the x-ray-tube-down configuration. When we used the magnification mode of the image intensifier, with its correspondingly smaller field size, the doses were further reduced to 46%, 32%, and 11% of the standard-configuration values. CONCLUSIONS: Use of the inverted-c-arm technique with the image intensifier as an operating table can significantly reduce radiation exposure to the surgeon and the patient during surgical procedures on upper extremities.

Arm↗

Primacy in causal strength judgments: the effect of initial evidence for generative versus inhibitory relationships.

The order in which people receive information has a substantial effect on subsequent judgment and inference. Our focus is on the order of covariation evidence in causal learning. The first experiment shows that the initial presentation of evidence suggesting a generative causal relationship (the joint presence or joint absence of cause and effect) leads to higher judged causal strength than does the initial presentation of evidence suggesting an inhibitory relationship (the presence of cause or effect in the absence of the other). Additional studies show that this primacy effect is unlikely to be due to fatigue or to an insufficient number of learning trials. These results are not readily explained by current contingency-based or associative theories of causal induction.

Adult↗

Methicillin-resistant Staphylococcus aureus infection in vascular surgical patients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is emerging as a major problem in vascular surgical practice. The aim of this study was to review the management of patients with MRSA infection complicating vascular surgical operations. METHODS: Data were obtained from the vascular audit, case notes, intensive therapy unit (ITU) notes, high dependency unit (HDU) notes and microbiological records of patients who underwent either arterial reconstruction (n = 464) or limb amputation (n = 110) between April 1994 and October 1998. RESULTS: Forty-nine vascular surgical patients developed clinical MRSA infection (9%). Clinical MRSA infection in patients who had undergone aorto-iliac reconstruction (n = 18) was associated with a 56% mortality (n = 10) and the most common infections were bacteraemia (55%) and pneumonia (50%). MRSA infection occurred in 17 patients who had undergone infra-inguinal bypass and was associated with a 29% mortality (n = 5). The most common site of MRSA infection was the groin wound (76%) leading to anastomotic dehiscence and death in one patient (11%) and necessitating wound debridement in 4 patients (22%). MRSA infection of the groin wound in the presence of a prosthetic graft (n = 3) led to anastomotic dehiscence in 2 patients, and graft excision in 2 patients. Similar complications were not observed in the presence of an underlying autogeneous long saphenous vein graft (n = 16). MRSA infection following major lower limb amputation (n = 14) was associated with death in 5 patients (36%). Wound infection in 10 amputees (71%) led to revision of the amputation to a higher level in 2 (14%) and wound debridement in 2 (14%). CONCLUSIONS: MRSA infection has a high mortality in vascular surgical patients in general, and following aorto-iliac reconstruction in particular. Autogeneous vein may confer some protection against local complications following groin wound infection. Strategies aimed at reducing the incidence of infection, including strict adherence to infection control procedures, may reduce the severity of this problem.

Adolescent↗

Causal status as a determinant of feature centrality.

One of the major problems in categorization research is the lack of systematic ways of constraining feature weights. We propose one method of operationalizing feature centrality, a causal status hypothesis which states that a cause feature is judged to be more central than its effect feature in categorization. In Experiment 1, participants learned a novel category with three characteristic features that were causally related into a single causal chain and judged the likelihood that new objects belong to the category. Likelihood ratings for items missing the most fundamental cause were lower than those for items missing the intermediate cause, which in turn were lower than those for items missing the terminal effect. The causal status effect was also obtained in goodness-of-exemplar judgments (Experiment 2) and in free-sorting tasks (Experiment 3), but it was weaker in similarity judgments than in categorization judgments (Experiment 4). Experiment 5 shows that the size of the causal status effect is moderated by plausibility of causal relations, and Experiment 6 shows that effect features can be useful in retrieving information about unknown causes. We discuss the scope of the causal status effect and its implications for categorization research.

Cognition↗

Plethysmography: the new wave in haemodynamic monitoring--a review of clinical applications.

The plethysmograph, a useful, non-invasive circulatory assessment capability featured on most modern pulse oximeters, provides a waveform representation of pulsatile peripheral blood flow, from which can be drawn assessments of both the peripheral and central circulation. Implementation and maintenance of plethysmography monitoring is straightforward and uncomplicated by virtue of its non-invasiveness. Yet despite its capabilities, ease of use and widespread availability it remains an underutilised data source. Diagnostic and monitoring capabilities of the device include heart rate and rhythm monitoring, detection of myocardial and valvular dysfunction, assessment of intra-aortic balloon pump performance when pressure waveforms are unobtainable, detection and measurement of pulsus paradoxus, improved performance of the Allen's test and detection of peripheral vascular diseases, peripheral vasoconstriction and developing shock. This paper describes the range of established applications of plethysmography, reviews pertinent literature and describes the directions in which, in the absence of supportive literature, clinical practice is finding applications.

Cardiography, Impedance↗

Developmental toxicity and toxicokinetics of two endothelin receptor antagonists in rats and rabbits.

Embryo-fetal development studies with toxicokinetic evaluations were conducted in rats and rabbits after oral or intravenous administration of two endothelin receptor antagonists. In the rat studies, females were administered SB-217242 (0.01-300 mg/kg/day) orally or SB-209670 (0.01-50 mg/kg/day) intravenously from days 6-17 postcoitus (pc). External and visceral fetal examinations were performed at necropsy on day 21 pc. Maternal body weight and food consumption were decreased only at 300 mg/kg/day SB-217242. Embryolethality was seen at 300 mg/kg/day SB-217242. Decreased fetal body weight occurred at 300 mg/kg/day SB-217242 and 50 mg/kg/day SB-209670. Dose-dependent increases in the mean percentage of fetuses per litter with malformations were seen at > or = 50 mg/kg/day SB-217242 and > or = 10 mg/kg/day SB-209670. Craniofacial, great vessel, heart, and thyroid were the predominant malformations. In the rabbit studies, females were administered SB-217242 (0.01-50 mg/kg/day) orally or SB-209670 (0.01-25 mg/kg/day) intravenously from days 6-20 pc. There was no drug-related effect on maternal body weight or food consumption. Embryolethality was observed at 50 mg/kg/day of SB-217242. Dose-related increases in the mean percentage of fetuses per litter with malformations were seen at > or = 10 mg/kg/day SB-217242 and > or = 10 mg/kg/day SB-209670. The malformations were similar to those observed in the rat studies, except that craniofacial development was not altered by SB-209670. The malformations observed are consistent with the pattern of endothelin-1 gene expression described in mouse embryonic pharyngeal arches and heart, and with the craniofacial and cardiovascular malformations observed in endothelin-1-deficient mice. Given the known role for endothelins in development, and concordant malformations in rats and rabbits observed in this study, teratogenicity is likely to be a class effect of endothelin receptor antagonists.

Abnormalities, Drug-Induced↗

Determination of the oxygen-18/oxygen-16 isotope ratios of sugar, citric acid and water from single strength orange juice.

The ratio of the stable isotopes of oxygen (18O/16O) has been measured in the sugar, citric acid and water from authentic single strength orange juices, originating from a number of different countries. The sugars and citric acid were recovered from the juices and their 18O/16O ratios were determined by pyrolysis/continuous flow-isotope ratio mass spectrometry (Py/CF-IRMS). The 18O/16O ratio of the fruit juice water was determined by the carbon dioxide/water equilibration method. The delta 18O/1000 values of 45 different sugars ranged from +29.1 to +38.8/1000 and 15 citric acids ranged from +18.9 to +25.4/1000. The delta 18O/1000 value of the water present in the same samples ranged from -2.1 to +7.8/1000. A correlation was evident between the delta 18O/1000 values of the sugar, citric acid and water from the juices. This information can be used to improve the assessment of the authenticity of commercial 'freshly squeezed' orange juices. The detection of the presence of reconstituted orange juice concentrate in 'freshly squeezed' orange juices was improved by 37% using regression analysis of the combined water and sugar delta 18O/1000 ratios when compared to the use of delta 18O/1000 ratios of fruit juice water alone.

Beverages↗

The role of screening blood tests in patients with arterial disease attending vascular outpatients.

OBJECTIVE: To evaluate the benefits of a policy of performing screening blood tests in new patients with arterial disease referred to the vascular outpatients department. METHODS: Clinical audit over a 12-month period of all new referrals with arterial disease to the vascular outpatients department at the Leicester General Hospital. RESULTS: Two hundred and seventy-two patients had at least one blood test performed at their outpatient visit. All of these patients had a full blood count performed, of which 21 results (21%) were abnormal. Further investigation of patients with abnormal results revealed one case of bladder cancer, one case of leukaemia and one patient with polycythaemia. Urea and electrolytes were measured in 269 patients (99%). Of these, 26 (10%) were expectedly abnormal in patients with known renal impairment. A further 27 patients (10%) were identified to have some degree of unrecognised renal impairment. Serum non-fasting glucose was measured in 252 patients (93%). There were 11 unexpectedly raised results, but further investigation of these patients only diagnosed one of these patients as diabetic. Serum cholesterol was measured in 201 patients (74%). One hundred and thirty-two patients (66%) had an abnormally raised serum cholesterol level. Of these, only 12 patients (6%) were known to have hyperlipidaemia. CONCLUSIONS: Screening new patients with arterial disease in vascular outpatients does identify significant abnormalities, in particular renal impairment and hyperlipidaemia. Correction of these abnormalities may reduce the morbidity associated with contrast induced nephrotoxic acute renal failure, and also contribute to secondary prevention of vascular events associated with raised lipids.

Adult↗

In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose.

Infection of macaques with attenuated simian immunodeficiency virus (SIV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists concerning the conditions necessary for the induction of this vaccine effect. We report that only a high dose of attenuated SIVmac protected macaques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000-20000 TCID50 of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deletion in the nef gene, essentially resisted superinfection with uncloned SIVmac. In two animals challenge virus was never detected by PCR and in one animal challenge virus was detected on one occasion only. Although animals given 2-200 TCID50 of attenuated virus were superinfected they were spared from the loss of CD4 cells seen in infected naive controls. Protection from superinfection did not correlate with immune responses, including the levels of virus-specific antibodies or virus-neutralizing activity measured on the day of challenge; although, after superinfection challenge, Nef-specific CTL responses were detected only in animals infected with high doses of attenuated SIV. Unexpectedly, cell-associated virus loads 2 weeks after inoculation were significantly lower in animals infected with a high dose of attenuated SIV compared to those in animals infected with a low dose. Our results suggest that the early dynamics of infection with attenuated virus influence superinfection resistance.

Animals↗

Arterial thrombosis: a complication of loop ileostomy.

Restorative proctocolectomy has become the surgical treatment of choice in ulcerative colitis. Most commonly, this is performed as a staged procedure which includes formation of a defunctioning loop ileostomy. High output loop ileostomies are associated with both local and systemic complications. We describe two patients with loop ileostomies who developed acute arterial thrombosis, a complication not previously described, thus further emphasizing the importance of careful management and early reversal of high output ileostomies.

Aged↗

Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa.

Good protection against systemic challenge in the SIVmac model of AIDS has been provided by prior infection with attenuated virus. To determine if such protection extends to intrarectal mucosal challenge two molecular clones, SIVmacC8 and SIVmacJ5, were used in this study. SIVmacC8 has an attenuated phenotype in vivo, due to a 12-bp deletion in the nef/ 3'-LTR, whereas SIVmacJ5 has a full size nef open reading frame and induces AIDS in infected macaques. The J5 molecular clone was shown to infect rhesus macaques following atraumatic intrarectal inoculation. The dynamics were similar to those following intravenous inoculation resulting in early, high, cell-associated viremia and seroconversion. Four macaques previously infected with the attenuated SIVmacC8 resisted superinfection with SIVmacJ5, following intrarectal inoculation. These animals also resisted intrarectal infection with an HIV/SIV chimeric virus (SHIV) composed of SIVmac239 expressing the HXBc2 env, tat, and rev genes, suggesting that immunity to the envelope proteins was unlikely to be involved in the superinfection resistance. Infection with the attenuated SIVmac generated cytotoxic T lymphocytes (CTL) detectable in the peripheral circulation, serum neutralizing antibodies, and SIV-binding antibodies in rectal fluids. SIVmacC8 proviral DNA was found in lymph nodes removed at necropsy but there was no evidence for local sequestration of challenge virus. SIV-specific CTL, were detected in gut-associated lymph nodes and may have a role in limiting superinfection following mucosal exposure.

Animals↗

The pharmacokinetics of topotecan and its carboxylate form following separate intravenous administration to the dog.

PURPOSE: To determine the relationship between topotecan and its ring opened hydrolysis product (SK&F 105,992) following intravenous administration of the two agents separately, and to determine the bio-availability of topotecan in female beagle dogs. METHODS: The pharmacokinetics of topotecan and SK&F 105,992 were determined following separate administration as 30 minute intravenous infusions in a cross-over design. Topotecan was also administered orally to the same dogs. RESULTS: When administered intravenously to dogs, SK&F 105,992 underwent interconversion to topotecan. Plasma concentrations of both topotecan and SK&F 105,992 appeared to decline multi-exponentially following i.v. infusion of either compound. A 2-compartment model was found to adequately characterize the data. CONCLUSIONS: The clearance of topotecan by other routes proceeded at a faster rate than its interconversion to SK&F 105,992, whereas the clearance of SK&F 105,992 by other routes was slower than the rate of its interconversion to topotecan. Any SK&F 105,992 formed in the GI tract did not appear to be well absorbed following oral administration of topotecan to dogs. The steady-state volume of distribution for topotecan was approximately 8- to 9-fold greater than that for SK&F 105,992 in the dog. After intravenous administration of topotecan, the amount of topotecan in the dog was much greater than that of the carboxylate, even though their respective plasma concentrations were similar. The bioavailability of topotecan, calculated from oral topotecan data or from SK&F 105,992 data, was approximately 50%.

Administration, Oral↗

Evening dosing is associated with higher plasma concentrations of pranlukast, a leukotriene receptor antagonist, in healthy male volunteers.

AIMS: To study the magnitude of differences in the pharmacokinetics of pranlukast, after morning and evening administration. METHODS: Pranlukast (300 mg) was administered to 12 healthy male volunteers on two separate occasions, either in the morning or evening. Both doses were given 30 min after a standard high fat content meal. Blood samples were collected up to 18 h postdose. Plasma was assayed by high performance liquid chromatography. Standard pharmacokinetic and statistical analyses were performed. RESULTS: Statistically significant (P < 0.05) increases were noted in AUC(o,t) (56%) and tmax (2.5 h) after evening administration. Cmax was 14% higher after evening dosing (95% C.I. 0.71-1.84). CONCLUSIONS: Pranlukast bioavailability is apparently increased after evening dosing as compared with morning administration. Higher night-time and early morning plasma concentrations may confer additional therapeutic benefit at a time when asthmatics are at greatest risk of developing bronchospasm.

Adult↗

The effect of azodicarbonamide concentrations on ethyl carbamate concentrations in bread and toast.

A series of baking experiments have been undertaken in order to test the proposition that the use of the flour improver azodicarbonamide influences ethyl carbamate concentrations in baked bread. Samples were prepared in a laboratory and contained 0, 20 and 45 mg azodicarbonamide/kg; 20 mg/kg reflecting normal commercial usage and 45 mg/kg the UK statutory limit. Samples incorporating 0 and 20 mg/kg of the additive were also prepared in a commercial bakery. Toast made from these breads was examined since it is known that toasting can lead to increased ethyl carbamate concentrations. Statistical analysis of the data indicated that, at 45 mg/kg, azodicarbonamide led to significant increases in ethyl carbamate concentrations in both bread and the toasts made from it. At 20 mg/kg some small increases in ethyl carbamate were seen for bread and this approached statistical significance for those samples made in the commercial plant. When these breads were toasted an increase in ethyl carbamate was observed but this was not attributable to the use of azodicarbonamide.

Azo Compounds↗