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Biomedical subjects

R Middleton

Publications and source records attributed to R Middleton.

At least 19 recordsLinked to original sources
PubMed2006

Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study.

BACKGROUND: Osteoarthritis (OA) of the knee is the most prevalent joint disorder. Previous studies suggest that bromelain, a pineapple extract, may be a safer alternative/adjunctive treatment for knee OA than current conventional treatment. AIM: To assess the efficacy of bromelain in treating OA of the knee. DESIGN: Randomized, double-blind placebo-controlled trial. METHODS: Subjects (n = 47) with a confirmed diagnosis of moderate to severe knee OA were randomized to 12 weeks of bromelain 800 mg/day or placebo, with a 4-week follow-up. Knee (pain, stiffness and function) and quality-of-life symptoms were reported monthly in the WOMAC and SF36 questionnaires, respectively. Adverse events were also recorded. The primary outcome measure was the change in total WOMAC score from baseline to the end of treatment at week 12. Longitudinal models were used to evaluate outcome. RESULTS: Thirty-one patients completed the trial (14 bromelain, 17 placebo). No statistically significant differences were observed between groups for the primary outcome (coefficient 11.16, p = 0.27, 95%CI -8.86 to 31.18), nor the WOMAC subscales or SF36. Both treatment groups showed clinically relevant improvement in the WOMAC disability subscale only. Adverse events were generally mild in nature. DISCUSSION: This study suggests that bromelain is not efficacious as an adjunctive treatment of moderate to severe OA, but its limitations support the need for a follow-up study.

Aged↗
PubMed2003

Improving the comparative map of porcine chromosome 9 with respect to human chromosomes 1, 7 and 11.

Conserved segments have been identified by ZOO-FISH between pig chromosome 9 (SSC9) and human chromosomes 1, 7 and 11. To assist in the identification of positional candidate genes for QTL on SSC9, the comparative map was further developed. Primers were designed from porcine EST sequence homologous to genes in regions of human chromosomes 1, 7 and 11. Porcine ESTs were then physically assigned using the INRA somatic cell hybrid panel (INRASCHP) and the high-resolution radiation hybrid panel (IMpRH). Seventeen genes (PEPP3, RAB7L1, FNBP2, MAPKAPK2, GNAI1, ABCB1, STEAP, AKAP9, CYP51A1, SGCE, ROBO4, SIAT4C, GLUL, CACNA1E, PTGS2, C1orf16 and ETS1) were mapped to SSC9, while GUSB, CPSF4 and THG-1 were assigned to SSC3.

Animals↗
PubMed2002

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study.

In a historical cohort study of all singleton live births in Northern Ireland from 1971-86 (n=434,933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age. High birth weight (> or =3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous miscarriage or increased gestation (> or =40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95% CI=0.48--0.94). Children born into more crowded households (> or =1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91 and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.

Abortion, Spontaneous↗
PubMed2000

GC-MS identification of sympathomimetic amine drugs in urine: rapid methodology applicable for emergency clinical toxicology.

A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, pseudoephedrine, and selegiline. In addition, two alpha-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary or secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10% fluoroanhydride in hexane, whereas the other sympathomimetic amines, including mazindol, were analyzed underivatized. Three different fluoroanhydrides, trifluoroacetic (TFAA), pentafluoropropionic (PFPA), and heptafluorobutyric (HFBA), and three different injection-port temperatures (160, 200, and 260 degrees C) were investigated. Both TFAA and PFPA gave sympathomimetic amine derivatives with essentially identical retention times, whereas HFBA gave longer retention times and better separation of individual compounds. The base fragmentation ion was noted to increase 50 amu (CF2) for each derivatized sympathomimetic amine as the length of the carbon-fluorine chain increased. Fragmentation ion abundance was maximized at an injection-port temperature of 260 degrees C, and this enhanced sensitivity coupled with the better chromatographic resolution of the individual sympathomimetic amines prompted the selection of HFBA as the derivatizing agent of choice. Assignments were made for the fragmentation ions produced by each derivatized drug. The developed method was adapted to analyze urine specimens that might be encountered in emergency toxicology testing. For identification of sympathomimetic amines requiring derivatization, 0.1 mL of the patient specimen had amphetamine-d5 and methamphetamine-d5 added as internal standard followed by adjustment of pH to 9.3 with borate buffer, extraction with 9:1 chloroform/isopropanol, centrifugation and separation of the organic phase, addition of 10% methanolic HCI and evaporation under nitrogen, reconstitution with HFBA reagent, and on-column derivatization during gas chromatographic-mass spectrometric (GC-MS) analysis. For those sympathomimetic amines not requiring derivatization, 1.0 mL of urine specimen had diazepam-d5 added as internal standard followed by the same extraction procedure and reconstitution accomplished with ethyl acetate. Because precolumn derivatization was eliminated and only 8 min was required for GC-MS analysis, complete analysis time was approximately 30 min, making the method suitable for clinical emergency toxicology purposes.

Emergency Service, Hospital↗
PubMed2000

Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group.

PURPOSE: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. MATERIALS AND METHODS: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least 1 course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. RESULTS: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. CONCLUSIONS: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.

Adjuvants, Immunologic↗
PubMed1999

Asbestos related mortality in Northern Ireland: 1985-1994.

BACKGROUND: The association between Belfast and research into the hazardous effects of asbestos exposure goes back many years. This paper aims to update previous papers and review the burden of asbestos related disease in Northern Ireland today. METHODS: A study was carried out of all deaths in Northern Ireland between 1985 and 1994 inclusive, in which an asbestos related disease was mentioned anywhere on the death certificate. RESULTS: During this 10 year period, 527 asbestos related deaths were recorded; 88 per cent of these were in men. A total of 410 (77.8 per cent) were registered as the primary cause of death but only 405 (76.9 per cent) of cases were the subject of an autopsy. Standardized rates of pleural cancer in males have been increasing at 3.2 per cent per year though the trend was not significant. Lower rates in the last two years may herald the commencement of a decline. Deaths were clustered around the Belfast estuary, the site of Northern Ireland's shipbuilding industry. High proportional mortality ratios were demonstrated for occupations associated with the shipbuilding and construction industries. Evidence is presented that casts doubt on the attribution of peritoneal cancers in females to asbestos exposure. If lung cancers are included, there may be an average of 81 asbestos related deaths in Northern Ireland every year. CONCLUSION: Asbestos related diseases continue to extract a heavy burden of ill health in Northern Ireland today. There are some indications that the upward trend may be on the wane but confirmation of this will have to await further data. Measures to reduce exposure in the workplace to both asbestos and to tobacco smoke are the only means of reducing this burden.

Aged↗
PubMed1997

Reliability of a comorbidity measure: the Index of Co-Existent Disease (ICED).

The reliability of an established comorbidity index (the Index of Co-Existent Disease) was tested using retrospective data from the case notes of elderly patients who had undergone total hip replacement. Inter-rater reliability was examined twice, first with two raters (n = 39) and then with three (n = 49). Intra-rater reliability was assessed using one rater (n = 45). Reasons for any lack of reliability were explored. The inter-rater reliability of the ICED was moderate (kappa 0.5-0.6). While the Functional Severity index performed well (kappa 0.6-1.0), the Index of Disease Severity subindex was less reliable (kappa 0.4-0.5). Differences between raters had an impact on the observed association between comorbidity and serious post-operative complications. Intra-rater reliability was excellent (kappa 0.9). Several reasons why inter-rater reliability was only moderate were identified, mostly related to uncertainties in applying the ICED. The reliability of the ICED needs to be improved before it is used more widely with retrospective data. This might be achieved by further clarification of the instructions for its use.

Activities of Daily Living↗
PubMed1997

Active compliance in robotic surgery--the use of force control as a dynamic constraint.

Robotic surgery can be carried out automatically by using a robot to move the cutting tool under position control. However, although the surgeon can observe the procedure on a visual display and has the ability to stop the operation in an emergency, he has little direct contact with the task. An alternative approach is to involve the surgeon more directly, by his moving a robot using active force control. The robot is then used to allow motion in preprogrammed regions, by the surgeon back-driving the robot motors, while preventing motion in prohibited areas. This active constraint robot (or ACROBOT) is described in this paper applied to knee surgery, in which the knee bones are accurately machined to allow the fitting of prosthetic knee implants. The ACROBOT is, however, ideally suited to a range of surgical procedure, because it allows the surgeon to feel the forces exerted during cutting and take appropriate action. This ability to be in direct control, while being constrained to cut within a permitted region, enhances safety and makes the system more acceptable to the medical community. The system of programmable constraint also allows the ACROBOT to provide the traditional benefits of robot surgery, namely the ability to machine complex geometrical surfaces very accurately and to make repetitive motions tirelessly. The system also has a potential for minimally invasive procedures. In knee surgery, for example, the robot could operate through a small incision in the skin and excise a volume into which a small, specially designed, unicompartmental prosthesis could fit.

Arthroplasty, Replacement, Knee↗
PubMed1996

Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens.

An automated high-performance liquid chromatographic method, benzodiazepines by REMEDi HS, was used to analyze benzodiazepines and their metabolites after beta-glucuronidase hydrolysis of 1-mL urine specimens from the following: 924 clinic and hospital patients whose specimens had previously been found to be presumptively positive using either EMIT or Triage immunoassay methodologies and 128 individuals whose specimens had screened negative by EMIT d.a.u.TM. REMEDi analyses did not correlate with the immunoassay results in 136 of the positive and three of the negative urine specimens. Gas chromatographic-mass spectrometric (GC-MS) confirmatory analyses were performed on these discordant specimens using 3 mL beta-glucuronidase-hydrolyzed urine followed by extraction with chloroform-isopropanol (9:1) and derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide. Two benzodiazepines, flunitrazepam and clonazepam, and their 7-amino metabolites were analyzed without prior derivatization. The analyses established 87% concordance between REMEDi and GC-MS versus 13% concordance with immunoassay for the subset. GC-MS analysis of these 142 specimens demonstrated two reasons for the nonconcurrence between REMEDi and EMIT: EMIT had given either false-negative or false-positive results and EMIT had given a positive result even though the determined metabolites were below the 200-ng/mL cutoff for the immunoassay and the 80-ng/mL cutoff for REMEDi. A total of 23 specimens were found to contain only lorazepam by REMEDi and GC-MS, 15 of which had been screened by Triage. A reevaluation of these 23 specimens by EMIT d.a.u. demonstrated that 11 were positive. This finding was in contrast to previous reports that EMIT will not detect lorazepam glucuronide in urine. An unexpected finding was the REMEDi identification and subsequent GC-MS confirmation of 7-aminoflunitrazepam, a urinary metabolite of flunitrazepam that is not available in the United States and that represented illicit use by four patients. A distinct advantage of REMEDi proved to be its capability in identifying demoxepam, a major metabolite of chlordiazepoxide; GC-MS analysis could not detect this metabolite because of its thermal decomposition to nordiazepam. To further evaluate the specificity of REMEDi, we conducted GC-MS analyses in a random fashion on 55 additional nondiscordant urine specimens that were identified as either positive or negative, as well as 22 specimens identified as containing 7-aminoclonazepam by REMEDi. Concurrence was observed between the two methods for all specimens, with the exception of one apparent false positive for alpha-hydroxyalprazolam by REMEDi. The reproducibility of the REMEDi method was found to be excellent; it was assessed by comparing results of 266 specimens that were reprocessed in different batches and for known calibrators and controls also processed with each batch. Study results demonstrated that the automated REMEDi assay for urinary benzodiazepines and their metabolites was comparable with GC-MS but had distinct advantages over GC-MS because of the following reasons: simplicity of the assay, less time required for analyses, and provision of additional information concerning the parent benzodiazepine.

1-Propanol↗
PubMed1996

The influence of osteoarthritis on the pattern of proximal femoral fractures.

The relationship between subcapital and trochanteric fractures and osteoarthritis was investigated to test the hypothesis that the presence of osteoarthritis would predetermine the site of the fracture. The authors reviewed 429 pelvic radiographs of patients with proximal femoral fractures. Osteoarthritis was found in 18 patients (4.2%). Sixteen patients followed the predicted fracture pattern of subcapital fracture and osteoarthritis of the other hip, or trochanteric fracture and osteoarthritis of the same hip. These results were statistically significant, supporting the hypothesis that patients with osteoarthritis of the hip who fall are likely to sustain a contralateral subcapital fracture or an ipsilateral trochanteric fracture.

Hip Fractures↗
PubMed1996

Ambulatory patient groups and redefining the roles of health care providers' delivery services in the USA.

Provides a review and analysis of the ambulatory patient groups classification system. Discusses a review of the history, development and implementation process. Concludes that in the ongoing efforts to move towards full-managed care in the not-so-distant future, ambulatory patients groups are another potential cost-cutting remedy for current health care providers and that future research into this issue is a must for public policy makers.

Ambulatory Care↗
PubMed1995

Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature.

GH secretion is primarily regulated by the hypothalamic-releasing hormones GHRH and somatostatin. Additionally, several neurotransmitters act at the hypothalamus and pituitary to modulate GH release. The agents commonly used in clinical practice to diagnose GH deficiency, such as arginine, insulin and L-dopa, act through the neural GH network. Many children with a poor GH response to conventional agents have a significant serum GH response to iv GHRH. GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. GHRP-2, an investigational drug, is one of the most potent members of the GHRP family. It has been shown to be effective in adults via the oral and intranasal as well as the iv route of administration. In this study, GH responses to GHRP-2 were compared with GH responses to other provocative agents in children of short stature. GHRP-2 was administered iv or intranasally to children with short stature. In the same subjects, GHRP-2 was administered iv in combination with GHRH. Twenty-four children undergoing evaluation for GH deficiency received at least one conventional agent (arginine, L-dopa/exercise, insulin) in addition to iv GHRH and GHRP-2. The GH responses to GHRH or GHRP-2 were similar in each child, and both were equally reliable predictors of pituitary reserve. The conventional agents used in GH testing were less likely to predict the capacity of the pituitary to release GH than were either GHRH or GHRP-2. There was no correlation between maximal GH response to standard tests with GH responses to GHRH or GHRP-2. A subset of the group of 21 children who had a robust response to iv GHRP-2 were later administered GHRH+GHRP-2 simultaneously. The GH response to GHRH+GHRP-2 was synergistic in this group of 12 children, similar to previously reported observations in adults of normal stature. Fifteen of the 21 children who had a robust response to the iv GH-releasing factors also received intranasal GHRP-2. All 15 of these children had a significant GH response to intranasal GHRP-2 over a dose range of 5-20 micrograms/kg per dose. The mean peak GH response to 15 micrograms/kg was 31.3 micrograms/L. The intranasal preparation was well tolerated.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1994

Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry.

A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study.

Aluminum↗
PubMed1992

Comparison of four methods for assessing airway bacteriology in intubated, mechanically ventilated patients.

A prospective evaluation of lower airway bacteriology from intubated, mechanically ventilated patients was performed by comparing the qualitative and quantitative recovery of bacteria using four different techniques. Twelve intubated, mechanically ventilated patients who satisfied accepted clinical criteria for the suspicion of ventilator-associated pneumonia were studied. Airway secretions were obtained from each patient by: (1) blind endotracheal aspiration (ET); (2) Accu-cath pulmonary culture catheter (Accu); (3) bronchoscopic protected specimen brush (BPSB); and (4) bronchoalveolar lavage (BAL). ET specimens were cultured semi-quantitatively (1+ to 4+) aerobically, and all other specimens were cultured quantitatively both aerobically and anaerobically. The BPSB recovered 9 organisms in > or = 10(3) colony forming units/ml, a standard number often used to indicate significant growth. Of these 9 organisms, 7 were recovered at > or = 10(3) cfu/ml by Accu, and 6 were recovered at > or = 10(4) cfu/ml by BAL. All 8 aerobic isolates recovered in > or = 10(3) cfu/ml by BPSB also were recovered by ET aspirate. Five of these were recovered in > or = 3+ semi-quantitative growth by ET aspirate. Of 30 organisms recovered in < 3+ semi-quantitative growth by ET aspirate, 28 were recovered in < 10(3) cfu/ml by BPSB, indicating a negative predictive value of 93%. Thus, it appears that these four methods provide reasonably similar qualitative and quantitative recovery of bacteria from the lower airways of intubated, mechanically ventilated patients. In addition, routine Gram's stain and semi-quantitative aerobic culture of endotracheal aspirate may provide useful information in patients with suspected ventilator-associated pneumonia.

Bacteria↗
PubMed1992

[Beta-ketothiolase deficiency: a case of ketoacidosis with hyperglycinemia].

Regarding a case of beta-ketothiolase deficiency revealed by ketoacidosis with hyperglycinemia, the authors show the way to diagnose and to treat this disease. Ketoacidosis without hyperglycemia or lactacidemia suggested this diagnosis. Gas chromatography-mass-spectrography revealed unusual urinary excretion of metabolic products of isoleucine. The enzymological study of fibroblasts confirmed the diagnosis. The treatment of acute episodes consisted of acidosis control and exclusive glucides intake before diagnosis. Afterwards, a controlled proditic diet and L-carnitine must be given and fasting must be avoided.

Acetyl-CoA C-Acyltransferase↗