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Biomedical subjects

R M Wilson

Publications and source records attributed to R M Wilson.

At least 37 records · Page 2Linked to original sources

Evaluation of cisatracurium, a new neuromuscular blocking agent, for tracheal intubation.

PURPOSE: The primary objective of this study was a blinded, randomized comparison of the recommended intubating dose of atracurium (0.5 mg. kg-1) with an approximately equipotent dose of cisatracurium (0.1 mg. kg-1) during N2O/O2/propofol/fentanyl anaesthesia. METHODS: Eighty ASA physical status 1 or 2 patients, 18-70 yr of age, within 30% of ideal body weight, scheduled for elective low to moderate risk surgical procedures were studied. Adductor pollicis evoked twitch responses were measured with a Grass FT 10 force displacement transducer (Grass Instruments, Quincy, MA) and continuously recorded on a Gould multichannel polygraph (Gould Instrument Systems, Cleveland, OH) after induction of anaesthesia. RESULTS: Increasing the initial dose of cisatracurium (from 0.1 to 0.15 and 0.2 mg. k-1, decreased mean time of onset (from 4.6 to 3.4 and 2.8 min, respectively), and increased mean time of clinically effective duration (45 to 55 and 61 min, respectively). Recovery to a T4:T1 ratio of 0.7 occurred approximately seven minutes following administration of the reversal agent neostigmine for all treatment groups. Intubation conditions were good or excellent in over 90% of patients in all treatment groups (two minutes after approximately 2 x ED95 doses of cisatracurium or atracurium and 1.5 minutes after 3 x and 4 x ED95 doses of cisatracurium). CONCLUSION: The intubation results reported in this study together with the combination of predictable recovery from neuromuscular block and apparent haemodynamic stability make cisatracurium a potentially useful muscle relaxant in clinical practice.

Adolescent↗

Insulin treatment of corticosteroid-associated hyperglycemia and its effect on outcome after forebrain ischemia in rats.

BACKGROUND: Recent studies have reported that dexamethasone worsens neuronal injury after brain ischemia. This effect is assumed to be secondary to drug-induced hyperglycemia. The current study used a rat model to test the hypotheses that insulin treatment of dexamethasone-induced hyperglycemia would result in a postischemic neurologic outcome that is: (1) better than that of hyperglycemic, dexamethasone-treated subjects; and (2) better than, or equal to, that of saline-treated control subjects. METHODS: Twenty-four halothane-anesthetized (1.0% inspired) rats were randomly assigned to one of three treatment groups (N = 8 in each group): (1) normoglycemic, placebo-treated rats (group P) received an intravenous saline infusion; (2) hyperglycemic, dexamethasone-treated rats (group D) received 2 mg/kg intraperitoneal dexamethasone at days, 1 day, and h before ischemia plus an intravenous saline infusion; and (3) normoglycemic, dexamethasone- and insulin-treated rats (group DI) received the same treatment as group D, plus an intravenous insulin infusion shortly before ischemia. Blood gases and acid-base status were maintained within normal physiologic ranges. Pericranial and rectal temperatures were maintained at normothermia. Forebrain ischemia of 10 min duration was produced using an established model. Neurologic function was assessed by a blinded observer at 24 and 48 h postischemia. Brain histopathology was assessed at the time of ischemia-related death or after the examination at 48 h. All 24 rats were included in the analysis of neurologic function; however, only 21 rats that survived for > or = 24h post-ischemia were included in the histologic analysis. RESULTS: Rats were well matched for systemic physiologic variables, with the exception of glucose concentrations. Plasma glucose concentration immediately before ischemia was as follows: group P = 129 +/- 8 mg/dl (mean +/- SD), group D= 344 +/- 29 mg/dl, and group DI = 123 +/- 17 mg/dl. At 48h postischemia, groups P and DI were minimally injured and had similar functional scores. In contrast, all group D rats died of cerebral ischemia. Histologic injury was significantly worse in group D than in either group P or DI, but did not differ significantly between groups P and DI. When all groups were combined, there was a significant correlation between neurologic function and total histopathology score ranks. CONCLUSIONS: In the current study, dexamethasone administration before brain ischemia resulted in a worsening of postischemic outcome that was relate to drug-induced hyperglycemia. Restoration of normoglycemia, using insulin, resulted in a functional outcome similar to that in group P, and an attenuation of dexamethasone-associated histologic injury.

Animals↗

The Quality in Australian Health Care Study.

A review of the medical records of over 14,000 admissions to 28 hospitals in New South Wales and South Australia revealed that 16.6% of these admissions were associated with an "adverse event", which resulted in disability or a longer hospital stay for the patient and was caused by health care management; 51% of the adverse events were considered preventable. In 77.1% the disability had resolved within 12 months, but in 13.7% the disability was permanent and in 4.9% the patient died.

Adolescent↗

Second derivative infrared spectroscopy as a non-destructive tool to assess the purity and structural integrity of proteins.

Second derivative infrared (IR) spectroscopy can be used as a quick, easy, reproducible, cost-effective, non-destructive tool by which to evaluate the purity and structural integrity of samples of water-soluble proteins from a variety of sources. For this study, second derivative IR spectra were collected at ambient conditions for aqueous (D2O) solutions of seven different commercial samples of the same enzyme, porcine pancreatic elastase (2.0 to 3.8 mg protein/100 microL D2O, pD = 5.4 to 9.1). As with other globular proteins possessing a large fraction of beta-structure, the amide I' region [1700-1620 cm-1] of the second derivative IR spectra for each of the seven elastase samples exhibits a characteristic pair of bands: one of weak intensity appears near 1684 cm-1; the other close to 1633 cm-1 is moderate-to-strong. However, one of the seven samples shows a striking decrease in the observed intensities of the amide I' bands relative to the 1516 cm-1 absorption, along with the appearance of a strong, new band at 1614 cm-1. These intensity disparities strongly suggest that this sample is of much lower quality than the others and clearly has an appreciable proportion of the protein present in a non-native state. In addition, minor differences evident in the position and relative intensity of some individual amide I' bands among the seven spectra imply that subtle variations exist in the conformation of the peptide backbone of the seven samples. For two of the samples, these small, but reproducible, changes seem to be correlated with marked losses of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of monovalent cations on the self-association of cytidylyl-(3-5')-guanosine and guanylyl-(3'5')-cytidine in aqueous solution.

The hydrogen-bonding, base stacking, and formation of extended aggregates has been investigated for salts of guanylyl-3'-5')-cytidine, GpC, and cytidylyl-(3'-5')- guanosine, CpG, in which the cation was Na+, K+, or tetramethylammonium (TMA+). Variable temperature studies were done at 2-70 degrees C on aqueous solutions at pD4 and 8 using 1H NMR and FTIR. At low temperatures it has been found that at pD 8 both GpC and CpG form Watson-Crick dimers which stack upon each other to form larger species. A slight cation effect is observed below 35 degrees C which has the order: TMA+ > Na+ > K+. This order suggests that the cations are interacting with the phosphate and interactions with the bases are unlikely. The 1H NMR spectrum for TMACpG at pD 4 has been assigned and exhibits chemical shift differences from those at pD 8 which are consistent with protonation of the N3 of the cytidine residue. Based on NMR line broadening, CpG at pD 4 has a greater degree of self-association at low temperature than it or GpC have at pD 8. A different type of hydrogen bonding and self-association occur in CpG at pD 4 compared to pD 8, but the structures are uncertain. Due to hemi-protonation of the cytidine N3, parallel G-G/C-C+ base paired dimers or G-tetrads may be forming.

Cations, Monovalent↗

Transmission of thyrotoxicosis of autoimmune type by sibling allogeneic bone marrow transplant.

This case report is on a 25-year-old male with acute myeloblastic leukaemia who achieved a remission after cytoxic therapy and whole-body irradiation. He received a bone marrow transplant from his human leucocyte antigen (HLA)-identical sister who had unsuspected autoimmune thyroid disease. Nine months later the bone marrow recipient developed thyrotoxicosis of autoimmune type at a time when his circulating lymphocytes were of 46XX karyotype. It is suspected that the thyrotoxicosis resulted from the transplantation of a clone of lymphocytes predisposed to the production of thyroid-stimulating autoantibodies.

Adult↗

Comparative analysis of the genetic associations of HLA-DR3 and tumour necrosis factor alpha with human IDDM.

Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ alleles, but a pathogenic role for TNF-alpha in the class III region of the MHC has also been implied. We therefore tested whether there was any independent association between a biallelic TNF polymorphism and IDDM. The TNF2 allele was present in 61 of 114 (54%) IDDM patients compared to 101 of 253 (40%) control subjects (odds ratio 1.73; p < 0.02). Stratification analysis in individuals matched for HLA-DR3 revealed, however, that this association was not independent of HLA-DR3 and is most likely to be a result of linkage disequilibrium between these alleles.

Adult↗

Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography.

New techniques of sural nerve photography and fluorescein angiography which are able to provide an index of nerve blood flow have been developed. Under local anaesthetic, 3 cm of sural nerve was exposed at the ankle using an operating microscope. Without disturbing the epineurium, vessels were identified and photographed at a standard magnification (x 30). These were independently graded by an ophthalmologist not otherwise involved with the study. Fluorescein angiography was then carried out on the exposed nerve. The fluorescein appearance time and intensity of fluorescence were quantified, using computer analysis of digitised images. Thirteen subjects with chronic sensory motor neuropathy, five non-neuropathic diabetic and nine normal control subjects were studied. The mean epineurial vessel pathology score of the neuropathic group was significantly higher than the combined normal control and non-neuropathic diabetic groups (p < 0.01). Direct epineurial arteriovenous shunting was observed in six neuropathic and one non-neuropathic diabetic patients and not in any of the normal control subjects. The nerve fluorescein appearance time was significantly delayed in subjects with chronic sensory motor neuropathy (51.5 +/- 12 s) compared to both normal (34.7 +/- 9 s, p < 0.01) and non-neuropathic diabetic subjects (33.4 +/- 11 s, p < 0.025). The mean intensity of fluorescence at 96, 252 and 576 s, was significantly lower in subjects with chronic sensory motor neuropathy compared with both of the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

A case of ocular ischaemic syndrome in a young insulin dependent diabetic male.

It is well known that diabetic patients are at an increased risk of the earlier development of significant atherosclerotic disease. We wish to report the case of a young insulin-dependent diabetic with an 18 months history of rapidly progressing 'diabetic' retinopathy who presented with right-sided weakness and was found to have severe carotid artery disease. We suggest that the sudden proliferation in his retinopathy was due to retinal ischaemia secondary to the carotid artery stenosis and we wish to present this as a case of ocular ischaemic syndrome in a young diabetic patient.

Adult↗

Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy.

Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80% age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p less than 0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p less than 0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcutaneous temperature rose significantly in normal subjects (p less than 0.01, mean increase 2.07 degrees C) and non-neuropathic diabetic subjects (p less than 0.001, mean increase 2.52 degrees C) but not in neuropathic subjects (mean increase 0.15 degree C). However, sural sensory conduction velocity increased by 1.2 m.s-1.degree C-1 following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m.s-1. degree C-1). The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.

Adult↗

The influence of aldose reductase on the oxidative burst in diabetic neutrophils.

Lucigenin-enhanced chemiluminescence was examined as an index of neutrophil superoxide production in four groups of 20 subjects: controls with/without infection and type 1 diabetics with/without infection. At 5 mM glucose there was no significant difference in chemiluminescence output between neutrophils from the four groups (P greater than 0.01). Increasing the in vitro glucose concentration from 5 to 20 mM produced an 8.75% reduction in superoxide in the combined control groups, compared with a 21.45% reduction in the diabetic subjects (P less than 0.01). With the addition of an aldose reductase inhibitor (Statil, ICI) to neutrophils from diabetic subjects, the suppression caused by an increase in glucose concentration to 20 mM was reduced to 4.5%. This value was similar to the controls (P greater than 0.01). Neutrophil aldose reductase activity, measured in 28 diabetic subjects was 0.024 +/- 0.003 U/10(8) cells (mean +/- SE). There was a significant correlation between aldose reductase activity and superoxide suppression (P less than 0.01, r = 0.64). These results suggest that aldose reductase is responsible for reduced superoxide production in diabetic patients and the addition of an aldose reductase inhibitor to the diabetic neutrophil restores superoxide output to control values.

Aldehyde Reductase↗

Cation-dependence of the self-association behavior of guanylyl-(3'-5')-guanosine.

The aggregation behavior of guanylyl-(3'-5')-guanosine, GpG, in the form of the tetramethylammonium (TMA), Li, Na, and K salts in aqueous solution has been investigated by NMR and FTIR techniques. The salts were prepared by a cation-exchange method. The ability of the cations to induce aggregate formation is TMA+ < Li+ < Na+ < K+, where TMA+ has only a weakly promoting action and K+ has a very strong effect. Three types of aggregates have been observed: (a) small aggregates which are in rapid exchange with respect to the NMR time scale; (b) intermediate-sized aggregates which are slow to exchange; (c) very large aggregates which can only be observed by FTIR. In all cases the aggregated species are held together by base stacking and guanine-guanine hydrogen bonding. A stoichiometry of 2 GpG per K+ has been determined by a 1H NMR titration of TMAGpG with KCl. Models have been proposed for the various-sized species. These include stacked dimers, stacked tetramers (similar to G-tetrads), and species in which K+ ion bridges between phosphates in separate tetramers.

Cations, Monovalent↗

Men's disclosure of HIV test results to male primary sex partners.

We evaluated disclosure of human immunodeficiency virus (HIV) antibody status to a main sex partner and the impact on the relationship in men who have sex with men and who are enrolled in the Acquired Immunodeficiency Syndrome (AIDS) Community Demonstration Projects cohorts. Eighty-nine percent of both seronegative and seropositive men disclosed the results to their main sex partner. Seventy percent of the seronegative men and 82% of the seropositive men who did so reported that the relationship remained "as strong as ever" after 6 months. Most men who did not disclose their test results to their main partner reported being "single" after 6 months.

Adult↗

Pea chloroplast genes encoding a 4 kDa polypeptide of photosystem I and a putative enzyme of C1 metabolism.

The nucleotide sequence of 3.2 kbp of pea chloroplast DNA located upstream from the petA gene for cytochrome f, and previously reported to contain the gene for a photosystem I polypeptide, has been determined. Three open reading frames of 587, 40 and 157 codons have been identified. Orf40 encodes a highly conserved, hydrophobic, membrane-spanning polypeptide, and is identified as the gene psaI for the 4 kDa subunit of photosystem I. Orf587 is an extended version of the gene zfpA previously identified as encoding a conserved putative zinc-finger protein. The product of orf587 shows extensive homology to an unidentified open reading frame cotranscribed with a gene for folate metabolism in Escherichia coli and local homology to a region of the beta subunit of rat mitochondrial propionyl-CoA carboxylase. It is suggested that the product of orf587 is an enzyme of C1 metabolism and is unlikely to be a regulatory DNA-binding protein. Orf157 potentially encodes an unidentified basic protein, but the protein sequence is not conserved in other plants.

Amino Acid Sequence↗

Diabetic ketoacidosis precipitated by genital herpes infection.

Diabetic ketoacidosis is frequently precipitated by infections. We report three cases in which ketoacidosis was induced by genital herpes infection. There is good evidence that early treatment with systemic Acyclovir is effective in patients with a first attack of genital herpes. Therefore genital examination should be considered in patients with diabetic ketoacidosis particularly when there are symptoms of genital herpes. During episodes of recurrence, diabetic patients need to monitor their blood sugars more frequently and adjust insulin requirements accordingly. We believe that this is the first description of ketoacidosis being associated with this increasingly common and recurrent infection.

Acyclovir↗

Neutrophil aldose reductase activity as a potential marker for neuropathy and cataract in diabetes.

Aldose reductase activity can be measured in the neutrophil and it has been proposed that this may be a marker for risk of complications in diabetes. We have studied aldose reductase activity in neutrophil, nerve, and lens in diabetic patients undergoing sural nerve biopsy or cataract extraction. A correlation was demonstrated between lens and neutrophil aldose reductase activity (r = 0.53, p = 0.01) but no correlations were demonstrated between nerve aldose reductase activities and nerve morphometry, nerve function or neutrophil aldose reductase activity. No significant difference was found between neutrophil aldose reductase activities in groups of patients with severe neuropathy, or cataract, or no complications (24 (interquartile range 16-32) vs 24 (16-40) vs 24 (16-40) nmol NADPH min-1 10(8)-cells-1). In a group of 56 Type 1 diabetic patients screened within 6 years of diagnosis, multiple regression analysis failed to show any relationship between neutrophil aldose reductase activity and abnormalities of neurophysiological function. These results suggest that neutrophil aldose reductase activity cannot be used as a marker for the development of cataract or neuropathy in diabetes.

Action Potentials↗

Neutrophil aldose reductase activity and its association with established diabetic microvascular complications.

Direct investigation of the polyol pathway is rarely possible in studies of human diabetes. A spectrophotometric assay has been developed for the measurement of aldose reductase and sorbitol dehydrogenase activity in the neutrophil. Neutrophil aldose reductase activity was increased in patients with Type 1 diabetes with complications (median 40 (interquartile range 28-48) u, where 1 unit of enzyme activity = nmol NADPH min-1 10(8)-cells-1) compared with those without complications (20 (16-36) u, p less than 0.01) and normal control subjects (20 (8-36) u, p less than 0.01). In Type 2 diabetes, patients with complications also had higher aldose reductase activity (40 (28-52) u) than those without complications (24 (16-36) u, p less than 0.01). There were no differences between patients without complications and normal control subjects. Sorbitol dehydrogenase activity was decreased in diabetic patients (p less than 0.02) but not significantly different between diabetic patients with and without complications.

Aldehyde Reductase↗