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Biomedical subjects

J Rawlings

Publications and source records attributed to J Rawlings.

At least 19 recordsLinked to original sources

Metal ion catalyzed hydrolysis of ethyl p-nitrophenyl phosphate.

15N isotope effects in the nitro group and 18O isotope effects in the phenolic oxygen have been measured for the hydrolysis of ethyl p-nitrophenyl phosphate catalyzed by several metal ions. Co(III)-cyclen at pH 7, 50 degrees C, gave an 15N isotope effect of 0.12% and an 18O one of 2.23%, showing that P-O cleavage is rate limiting and the bond is approximately 50% broken in the transition state. The active catalyst is a dimer and the substrate is presumably coordinated to the open site of one Co(III), and is attacked by hydroxide coordinated to the other Co(III). Co(III)-tacn under the same conditions shows a similar 15N isotope effect (0.13%), but a smaller 18O one (0.8%). Zn(II)-cyclen at pH 8.5, 80 degrees C, gave an 15N isotope effect of 0.05% and an 18O one of 0.95%, suggesting an earlier transition state. The catalyst in this case is monomeric, and thus the substrate is coordinated to one position and attacked by a cis-coordinated hydroxide. Eu(III) at pH 6.5, 50 degrees C, shows a very large 15N isotope effect of 0.34% and a 1.6% 18O isotope effect. The large 15N isotope effect argues for a late transition state or Eu(III) interaction with the nitro group, and was also seen in Eu(III)-catalyzed hydrolysis of p-nitrophenyl phosphate.

Catalysis↗

Nutrition in the elderly hospital patient Nottingham studies.

Forty percent of elderly hospital admissions in the UK are undernourished, half severely so. Most continue to lose weight in hospital. not only because of disease, but also because of failure to identify and treat malnutrition and due to shortcomings in hospital food provision, upon which most patients depend for their nutritional care. Our studies have shown that more than 40% of food set before patients is left, and therefore wasted. This means that elderly patients are taking less than 70% of their energy (30-35 kcal/kg/day), and protein (1 dram/kg/day) requirements. Catering strategies, such as provision of smaller volume, high energy and protein density meals with snacks and, if necessary, proprietary oral supplements, have been shown not only to improve nutritional status of patients, but to result in improved clinical outcome. Our work has shown a relationship between malnutrition and loss of thermoregulation, which is reversed by appropriate feeding. We have also described the beneficial effects of overnight nasogastric tube feeding in undernourished patients with fractured femur. Like others, we have used a percutaneous endoscopic gastrostomy in the management of elderly patients with cerebrovascular and motor neurone disease, and have published audits of outcome in this field.

Aged↗

Urea kinetics of a carnivore, Felis silvestris catus.

The effect of two levels of dietary protein energy, moderate (20%; MP) and high (70%; HP), on urea kinetics in eleven domestic cats was studied. After a 3-week prefeed, a single dose of [(15)N(15)N]urea was administered, and urine and faeces collected over the subsequent 5 d. For each 24 h period, total urea and enrichment of [(15)N(15)N]- and [(15)N(14)N]urea in urine were determined, and a model applied to calculate urea production, entry into the gastrointestinal tract, recycling to urine or faeces and, by difference, retention by the body and potentially available for anabolism. Urea production and excretion increased with dietary protein level Most of the urea produced was excreted, with only a small proportion entering the gut, and with the pattern of urea disposal not significantly different between the HP and MP diets. Thus, the percentages of urea production available to the gut were 15% (MP) and 12% (HP), of which 57% (MP) and 59% (HP) was recycled in the ornithine cycle, 40% (MP and HP) was potentially available for anabolism and the rest lost as faecal N. As a percentage of urea produced the amount potentially available for anabolism was very low at 6.41% (MP diet) and 4.79% (HP diet). In absolute terms urea entering the gut, being recycled in the ornithine cycle and potentially available for anabolism was significantly higher on the HP diet These results show that cats operate urea turnover, but at a lower rate, and with less nutritional sensitivity than has been reported for other species.

Animals↗

Sumatriptan treatment for migraine in a health maintenance organization: economic, humanistic, and clinical outcomes.

This study was undertaken to assess the impact of 12 months of sumatriptan therapy (6 mg subcutaneously) for migraine on health care use, health-related quality of life, productivity, patient satisfaction with the medication, and clinical efficacy in a health maintenance organization (HMO). One hundred forty-eight patients received open-label sumatriptan for 12 months for the treatment of migraine. Medical records were reviewed to obtain information on the frequency of migraine-related health care use during the 12 months before and during sumatriptan treatment. Patients completed questionnaires on their productivity at work, health-related quality of life, and satisfaction with medication at baseline and after 3, 6, and 12 months of sumatriptan treatment. For each migraine, patients recorded pain severity scores before and after taking sumatriptan and the time between dosing and onset of meaningful relief. Sumatriptan was associated with significant reductions in migraine-related use of general outpatient services, telephone calls, urgent care services, and emergency department visits (P < 0.05); a significant increase in the use of pharmacy services (P < 0.05); and significant and sustained improvements in health-related quality-of-life scores compared with baseline (P < 0.001). Patients lost significantly less time from work and were significantly more satisfied with sumatriptan compared with their usual therapy (P < 0.05). Two hours after dosing, 81% of patients experienced reduction of moderate or severe pain to mild or no pain, and 90% of all patients experienced meaningful relief of pain. The use of sumatriptan for 12 months in an HMO was associated with reductions in health care use and improved health-related quality of life, productivity, and patient satisfaction with medication.

Adult↗

New reference reagent for the quality assurance of anti-D antibody detection.

A UK BTS-NIBSC freeze-dried anti-D preparation has been prepared and used to monitor the performance of routine antibody detection tests and of the test operators. With the day-to-day use of this preparation, adverse changes in test performance and in test operator may be detected and appropriate action taken before the effect becomes significant. Two dilutions of this preparation have been defined, one which should be detected unequivocally in every test; the other, more dilute, may not be detected in every test but is used to monitor changes in performance. Experience with the use of this preparation is reported from three test centres undertaking routine antibody detection tests. By monitoring results over a series of working days, significant differences were noted in operator performance within one test centre, as was a reduced sensitivity of a given test system within one test centre compared with the same system in the other test centres. These differences were detected only by monitoring the results obtained with this preparation.

Coombs Test↗

Long-term outcome and cost-effectiveness of parenteral nutrition for acute gastrointestinal failure.

Although there are several published audits of long-term home parenteral nutrition for chronic gastrointestinal failure, there is little data concerning the long-term outcome following prolonged in-patient parenteral nutrition for an episode of acute gastrointestinal failure. Between 1983 and 1 July 1993, 162 patients received total parenteral nutrition (TPN) in our unit for acute gastrointestinal failure for a total of 4997 patient days and using 192 central venous catheters. Over the 10 years there were 11 mechanical complications resulting in one death. Although the overall catheter infection rate was 5.7%, in the last 4 years it was 0%, associated with a reduction in the frequency of site dressing and change of giving set from three times to once weekly. All patients had lost more than 10% of their body weight before TPN. In the non-malignant group, fed for more than 21 days (mean 50 days), the 10-year survival was 74% at a cost of 4723 pounds sterling per year of life saved. In the malignant group, the 5-year survival was 27% at a cost of 8351 pounds sterling per year of life saved. These costs compare favourably with other technologies, such as dialysis for acute renal failure. Better patient selection, fewer complications and lower costs are obtained when this treatment is carried out by an expert team.

Journal Article↗

Characterization of isomers of monoamminechromium-ATP and their use in mapping enzyme active sites.

Twelve isomers formed by the reaction of monoamminechromium(III) with ATP have been synthesized. Isomerism in this system results from chirality around the beta-phosphorus of the ATP, the position of the ammonia ligand, the relative orientation of the ammonia and the AMP, and the presence of ring-puckering conformers. By using chromatography on cross-linked cycloheptaamylose, reverse-phase C-18 HPLC, and cation-exchange FPLC, these isomers have been separated and purified. Their structures have been identified by (1) cleavage by periodate, followed by elimination in the presence of diethylenetriamine and subsequent phosphate insertion to give lambda, delta, or meso facial monoamminechromium tripolyphosphate with molar ellipticities of +240, -240, or 0 deg cm2 dmol-1 at 550 nm, respectively, (2) cleavage by nucleotide pyrophosphatase to give meridional or facial monoamminechromium pyrophosphate, (3) spectral data, and (4) rates of interconversion of isomers. All possible isomers are seen except those with ammonia syn to AMP. Since the substitution of ammonia for water in the inner coordination sphere appears to diminish affinity for enzymes when the ammonia is in contact with the protein but not when it faces the solvent, these isomers are useful for mapping of enzyme active sites. Their use as probes of enzyme structure is illustrated by their behavior with yeast hexokinase.

Adenosine Triphosphate↗

Audit of outcome of long-term enteral nutrition by percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is the preferred method for administration of long-term enteral tube feeding. However, most published studies describe only short-term follow-up in any detail. We report the long-term outcome and complication rate after PEG insertion in 49 patients (mean [SE] age 64 [2] years) whose mean length of PEG feeding was 175 days (range 30-560). Data were collected prospectively. PEG insertion was technically successful in all cases, with a procedure-related mortality of 2%. Early (< 30 days) mortality and morbidity were 8% and 22%, respectively. Of 45 patients surviving for more than 30 days, 76% were able to return home and 6 patients were eventually able to revert to oral feeding. There were 27 late complications: 2 site infections, 17 mechanical problems, and 8 episodes of gastrointestinal dysfunction. 51% of patients had no problems at all and 22% had 2 or more complications. 47% of complications required a hospital visit for resolution. Long-term enteral feeding by PEG was safe, effective, and had a low complication rate. Our patients were managed by a specialist nutrition team, a policy that may reduce the complication rate and hospital visits for patients being fed at home, and allow early discharge of dysphagic patients, thereby reducing costs.

Aged↗

Lyme borreliosis in Texas.

Lyme borreliosis is a protean infection caused by B burgdorferi, a recently recognized arthropod-borne spirochete. The disease is generally acquired during warm weather, and its onset is characterized by a skin lesion, EM, and flulike symptoms. Neurologic, cardiac, and/or rheumatologic abnormalities may emerge weeks, months, or years later. In the absence of the pathognomonic skin lesion, determination of antibody response is currently the most practical laboratory aid in diagnosis. However, clinical judgement is necessary for the correct interpretation of laboratory results because false-positive and false-negative results are common. Antibiotics remain the mainstay of therapy. Longer courses of antibiotic therapy than those previously recommended may be needed to obtain a cure, particularly in later stages of the illness.

Anti-Bacterial Agents↗

Structures of the monohydrate and dihydrate of (bidentate pyrophosphato) trans-diammine cis-diaqua chromium (III).

(OC-6-32)-Diamminediaqua [pyrophosphato(3-)]chromium(III) monohydrate, [Cr(NH3)2-(H2O)2(HP2O7)]. H2O, Mr = 315.1, triclinic, P1, a = 7.127 (2), b = 8.390 (2), c = 9.619 (2) A, alpha = 72.14 (2), beta = 98.86 (2), gamma = 76.98 (3) degrees, V = 517.7 (3) A3, Z = 2, Dx = 2.02 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 129 cm-1, F(000) = 322, T = 293 K. (OC-6-32)-Diamminediaqua[pyrophosphato(3-)]-chromium(III) dihydrate, 0.5( [Cr(NH3)2(H2O)2-(HP2O7)].2H2O), Mr = 0.5(333.1), monoclinic, C2/m, a = 13.118 (3), b = 12.101 (3), c = 7.436 (2) A, beta = 105.09 (2) degrees, V = 1139.7 (3) A3, Z = 8, Dx = 1.94 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 118 cm-1, F(000) = 684, T = 293 K. The structures were solved by the multi-solution technique and refined by the method of least squares to yield a final R index of 0.057 for 986 reflections in the monohydrate and a final R index of 0.043 for 1030 reflections in the dihydrate. The six-membered chromium pyrophosphate chelate ring is in a boat conformation for the monohydrate with an intramolecular hydrogen bond between an ammonia proton and a pyrophosphate O atom. In the dihydrate, the chelate ring is bisected by the mirror plane resulting in an unusual planar chelate ring conformation which does not permit intramolecular hydrogen bonding.

Chromium↗

Low anthropometric indices in elderly females with fractured neck of femur.

Anthropometric measurements were made in 3 groups of elderly females (1) with fractured neck of femur, (2) those admitted to acute medical and geriatric wards, and (3) healthy women in the community. Mid-arm circumference was different in the three groups with mean values of 22.8 +/- 0.21 cm, 25.9 +/- 0.41 cm and 28.6 +/- 0.27 cm respectively; (p < 0.001 for all comparisons). Triceps skinfold thickness was 24.7 +/- 0.70 mm in the healthy elderly but only 13.0 +/- 0.59 mm in the fracture group (p < 0.001). Fractured femur patients are therefore thinner than both healthy controls and unselected elderly female medical in-patients. These differences are most apparent in anthropometric indices dependent on body fat and this may be significant in terms of the aetiology of fractured femur.

Journal Article↗

Triamminemonoaquocobalt(III) complexes of pyrophosphate and adenosine diphosphate (ADP).

Cobalt(III)H2O(NH3)3 pyrophosphate has been shown by proton and 31P nuclear magnetic resonance (NMR) to be a facial bidentate complex. Cobalt(III)H2O(NH3)3 adenosine diphosphate has been resolved into lambda and delta isomers by chromatography on cycloheptaamylose. Both the lambda and delta forms are a pair of isomers that are not separated by cycloheptaamylose, reverse phase high-pressure liquid chromatography (HPLC), or cation exchange chromatography. These isomers presumably represent syn- and anti-arrangement of coordinated water and adenosine.

Adenosine Diphosphate↗

Cross-reaction of immune sera from patients with rickettsial diseases.

Rickettsia rickettsii and Rickettsia conorii are the causative agents of two common and serious diseases, Rocky Mountain spotted fever and Mediterranean spotted fever, respectively. In patients naturally infected with either of these organisms, antibodies are produced which cross-react with antigens of the other so extensively that diagnostic tests usually cannot identify the causative agents. The results of this study indicate that serodiagnostic tests with antigen from one of these two organisms could be used to detect antibodies in patients with either of the two rickettsial diseases.

Antibodies, Bacterial↗

Overnight nasogastric tube feeding.

Overnight nasogastric tube feeding allows the patient freedom for normal daytime activities and exercise, essential components of rehabilitation. In order to avoid disturbed nights through frequent micturition we have kept the volume of feed to a minimum. Two types of feed have been used: 1. A supplementary isosmolar feed containing 1000 kCals in 1 litre. 2. A concentrated low volume (404 mosm/kg) feed supplying 1800 kCals including 60 g of nitrogen in 1 litre. Both were delivered via a fine bore tube (internal diameter 1 mm) by continuous infusion from a 1-1.5 litre reservoir using a rotary pump. Feed 1 was given to 64 undernourished elderly female patients (group 1) with fractured neck of femur, the tube being tolerated by 78%; 47 patients in this group were fed for more than 5 days. Feed 2 was given to 10 patients in hospital (group 2) and 8 patients at home (group 3). Few side effects were encountered, the hyperosmolar feed causing no diarrhoea, nausea or hyperglycaemia, emphasising the importance of osmoles per unit time rather than per unit volume. Voluntary oral intake was neither impaired nor increased during the period of tube feeding in group 1, in whom anorexia and thinness were longstanding. In group 2, with recent onset of anorexia and weight loss, tube feeding disinhibited appetite, resulting in a doubling of voluntary oral intake. Improvement in anthropometric and biochemical nutritional parameters was seen in all patients. Clinical improvements e.g. closure of fistulae were also observed. This paper describes the results of our trial of both these options in patients treated in hospital or at home.

Journal Article↗