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Biomedical subjects

C Chaloner

Publications and source records attributed to C Chaloner.

18 recordsLinked to original sources
PubMed2003

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use.

OBJECTIVE: To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines. METHODS: All patients under follow-up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow-up, were used to identify which patients should be receiving HAART according to the guidelines. RESULTS: One thousand two hundred and sixty-four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/ micro L and over 80% had previously had a viral load above 4 log10 HIV-1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty-five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it. CONCLUSION: Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

Adult↗
PubMed2001

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Antiretroviral Therapy, Highly Active↗
PubMed1995

Evidence of toxic metabolite stress in black South Africans with chronic pancreatitis.

We report the results of a further study to test our hypothesis that toxic metabolite stress is germane to heightened free radical activity and hence to the genesis of chronic pancreatitis. Consecutive black South African patients with clinically quiescent chronic pancreatitis were studied, provided that the diagnosis had been made within the previous 2 years and that they did not have overt liver disease. All of them had been advised to stop drinking alcohol. Analysis of an early morning sample of urine showed a lower ratio of inorganic to ester sulphate (P < 0.001) and a higher ratio of D-glucaric acid to creatinine (P < 0.02) in the group of 14 patients than in 15 local controls, while plasma analysis showed a lower concentration of glutathione (GSH) in the patients (P < 0.001). This evidence of increased utilisation of phase II conjugative pathways of xenobiotic disposal was in keeping with on-going toxic metabolite stress from heightened phase I oxidative metabolism in the group of patients. Parallel studies of theophylline pharmacokinetics showed heightened drug clearance compatible with induced cytochrome P-4501A2 in two patients, whereas increased activity of gamma-glutamyl transferase in serum suggested persisting induction of P-4502E1, as by ethanol, in several others. The contemporaneous increases in free radical activity and utilisation of xenobiotic disposal pathways in Sowetan Africans with chronic pancreatitis is in line with the toxic metabolite concept of disease pathogenesis.

Adolescent↗
PubMed1995

A preliminary report on urinary BT-PABA/PAS excretion index, serum pancreatic isoamylase and faecal chymotrypsin tests of pancreatic dysfunction in Sowetan Africans.

The steady increase in chronic pancreatitis among black Africans at Soweto, RSA, in the past 40 years necessitates an objective and non-invasive test to detect the disease at an early stage. Given the biphasic nature of the disease--secretory hyperfunction with periodic active inflammatory episodes followed by steady exocrine impairment--we assessed three potential aids. Urinary BT-PABA/PAS excretion index (PEI), serum pancreatic isoamylase (PIA) and faecal chymotrypsin activity (FCA) were measured in the following groups: 16 outwardly healthy hospital workers, 16 consecutive patients with calcifying chronic pancreatitis and 19 with abdominal pain ascribed to other conditions (disease controls). (1) Healthy controls had lower PEI than those at Manchester, UK, or Madras, India, from subclinical acinar loss--as shown by lower PABA recovery whereas intestinal absorptive capacity was maintained, as shown by recovery of PAS. (2) Using the popular cut-off for PEI (0.75) only 9 of 14 patients with chronic pancreatitis were identified (sensitivity 64%, 2 tests unsatisfactory), while a value of less than 0.54, the mean -2 S.D. in local controls, yielded sensitivity of 50%. (3) If PEI of less than 0.75 or PIA outside the reference range was taken to indicate the disease, 5 of 9 disease controls would have been classed as chronic pancreatitis (among those with both tests satisfactory): retrospective ultrasound scans did not identify these. (4) Although FCA was less than the preselected cut-off, 5 units/g, in every patient with chronic pancreatitis (100% sensitivity) its poor predictive value was indicated by low specificity: subnormal levels in 4 of 14 and 6 of 16 healthy controls or disease controls, respectively, most of whom had near-normal values of PEI, PIA or both. (5) Collectively, these results suggest a high frequency of subclinical chronic pancreatitis at Soweto, but also that the combination of tests required to identify it may prove impractical--whether in field surveys or hospital practice.

4-Aminobenzoic Acid↗
PubMed1995

Evidence for early oxidative stress in acute pancreatitis. Clues for correction.

Pancreatic oxidative stress with depletion of pancreatic glutathione is an early feature in all tested models of acute pancreatitis, and sooner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisystem organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it from high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acute abdominal crises where the proportion of patients with admission Apache II scores < or > 8 was similar). These changes were accompanied by subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001), beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar ratio to cholesterol). Paradoxically, the plasma concentration of S-adenosylmethionine was elevated (p = 0.02), suggesting that this proximate bioactive metabolite of the essential amino acid had backtracked because its intracellular metabolism down the methionine trans-sulfuration pathway toward glutathione synthesis was disrupted. The aberrations transcended putative etiological factor, duration of symptoms, or disease severity. We conclude: (1) that oxidative stress has pervaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient antioxidant profiles at this stage are consistent not only with compromised intracellular capacity to synthesize/refurbish glutathione, but also vulnerability of intra- and extracellular lipid targets.

Acetylcysteine↗
PubMed1995

Attitude to treatment and direction of interest of forensic mental health nurses: a comparison with nurses working in other specialties.

The attitudes of nurses working within forensic psychiatry are often perceived as being custodially oriented. Working on this commonly held assumption the authors hypothesized that nurses working within a physically controlled environment such as a Regional Secure Unit would hold more conservative/biological attitudes toward treatment, and would be more 'object'-oriented (as opposed to 'psychologically' oriented) than those working in less physically controlled clinical areas. [For the purpose of this paper the term 'Regional Secure Unit' is used to describe the medium secure facilities that were included in this study, although one of the units did not serve a wholly regional function.] This paper outlines a study that attempted to examine this hypothesis. A total of 84 nurses from three clinical specialties (Regional Secure Units, Acute Admission Wards and Drug Dependence Units) completed the Attitude to Treatment Questionnaire (ATQ) and the Direction of Interest Questionnaire (DIQ) (Caine et al. 1981). Each nurse also completed a demographic information questionnaire, supplying details of age, professional experience and educational attainment. The results indicate no significant differences on measures used between specialty groups. Significant positive correlations were found between age and conservatism on the ATQ, and between ATQ conservatism and DIQ object centredness. Implications of these results are discussed and suggestions for future research are made.

Attitude of Health Personnel↗
PubMed1992

The BT-PABA/PAS test in tropical diabetes.

A 'screening' test is needed to identify patients with chronic pancreatitis among diabetics in tropical field surveys. We have examined the potential diagnostic yield of the BT-PABA/PAS test of exocrine pancreatic function in this setting. The recoveries of both PABA and PAS in eight healthy controls from Madras, south India, were lower than in controls from Manchester, north west England (mean +/- S.D., 51 +/- 11 vs. 79 +/- 7%, P < 0.001 for PABA; 52 +/- 11% vs. 81 +/- 7%, P < 0.001 for PAS) but the % PABA/PAS excretion index (PEI) was similar (0.96 +/- 0.14 vs. 0.96 +/- 0.06). Using a cut-off value of 0.75 for the PEI in a study group including eight patients with chronic pancreatitis and 26 with primary forms of diabetes, test sensitivity was 75%, specificity 92%, positive predictive value 75%, negative predictive value 92% and efficiency 88%.

4-Aminobenzoic Acid↗
PubMed1991

Spectrofluorimetric determination of urinary p-aminobenzoic and p-aminosalicylic acids in the BT-PABA/PAS test of pancreatic function.

Spectrofluorimetry was investigated as an alternative to HPLC for determining p-aminobenzoic acid and p-aminosalicylic acid in the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid test of pancreatic exocrine function. Urine specimens were hydrolysed for 30 min in 4 M NaOH at 100 degrees C. The fluorescence of p-aminobenzoic acid was measured in dimethyl sulphoxide solution (lambda ex = 300 nm, lambda em = 340 nm) and that of p-aminosalicylic acid in sodium acetate buffer, pH 4.0 (lambda ex = 297 nm, lambda em = 394 nm). The linear range was 0.038-8 mM for p-aminobenzoic acid and 0.051-12 mM for p-aminosalicylic acid, within-batch precision was 2.2% and 5.5%, respectively, and the entire analysis could be completed within 40 min. Although not eliminated, drug interference was greatly reduced in comparison with colorimetry. In 23 consecutive pancreatic function tests there was an excellent correlation between the p-aminobenzoic acid/p-aminosalicylic acid excretion index obtained by fluorimetry and the results from HPLC analysis (y = 0.914x + 0.070, r = 0.987, p less than 0.001). The method is simple, cost-effective and may be particularly valuable in developing countries having a high incidence of chronic pancreatitis.

4-Aminobenzoic Acid↗
PubMed1990

Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis.

Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median 69 (range 39-114) vs 45 (33-56) ml h-1 kg-1, p = 0.003]. In keeping with this finding, detailed social histories identified a higher exposure level in the patients to xenobiotics that are inducers of cytochrome P-450I and/or yield reactive metabolites upon processing thereby (score 7, 4-11 vs 3, 2-9, p = 0.002). However, the concentration of D-glucaric acid in urine, as a marker of phase II conjugating pathways of drug metabolism, was similar in patients and controls. This pattern of drug metabolism could predispose to oxidant stress: hence micronutrient antioxidant supplements may have therapeutic (or even prophylactic) value in tropical chronic pancreatitis.

Adolescent↗
PubMedDate not supplied

The developing role of the forensic community nurse.

Mental health professionals are increasingly concerned with the consequences of clinical judgement errors. Such concern has led to an increase in requests for specialist advice from forensic mental health care teams. Consequently, the demand for forensic community mental health nurses (FCMHNs) to provide specialist advice and reports has increased. Such advice can be significant in planning and delivering care.

Community Health Nursing↗
PubMedDate not supplied

The final frontier.

Explore the source record for details and available documents.

Brain Death↗