Search PubMed⌕ Search

Biomedical subjects

A C Harrison

Publications and source records attributed to A C Harrison.

At least 19 recordsLinked to original sources
PubMed2002

Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis.

BACKGROUND: Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. METHODS: In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. RESULTS: Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p<0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p<0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. CONCLUSIONS: In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed.

Adolescent↗
PubMed2000

Studies of L-arginine transport in bovine aortic endothelial cells.

We have previously demonstrated that p(1),p(4)-diadenosine 5'-tetraphosphate induces the release of NO and modulates the uptake of L-arginine by bovine aortic endothelial cells (BAEC) [Hilderman, R. H., and Christensen, E. F. (1998) FEBS Lett. 407, 320-324; Hilderman, R. H., Casey, T. E., and Pojoga, L. H. (2000) Arch. Biochem. Biophys. 375, 124-130]. In this communication we characterize the uptake of L-Arg by BAEC. L-Arg is transported into BAEC by at least two different transporter systems. One transporter system is protein synthesis dependent, and L-Arg transported by this system is incorporated into proteins. The second transporter system involved in L-Arg uptake is protein synthesis independent, and uptake occurs by facilitated diffusion. The L-Arg transported by facilitated diffusion is metabolized into L-argininosuccinate. Homologous and heterologous competition uptake studies were performed using a fixed concentration of radiolabeled L-Arg, L-lysine, and L-leucine with varying concentrations of competing nonradiolabeled amino acids. The results of these competition uptake studies are consistent with the protein-synthesis-dependent uptake of L-Arg taking place through a transporter system that is highly specific for L-Arg and with the facilitated diffusion uptake taking place through a transporter that is specific for L-Arg and L-Leu.

Adenosine Triphosphate↗
PubMed1999

Mycobacterial cervical adenitis in Auckland: diagnosis by fine needle aspirate.

AIMS: To evaluate the role of fine needle aspiration (FNA) in the diagnosis of tuberculous and non-tuberculous mycobacterial cervical adenitis in Auckland, and to examine the demography of these conditions. METHOD: We reviewed the medical records of cases of mycobacterial adenitis in the Auckland region between 1991-1994. Cases were identified by cross-checking the reference mycobacteriology laboratory records, all hospital cytology reports from cases who had an FNA taken from the neck region and hospital discharge diagnosis databases. RESULTS: Twenty-two cases of M tuberculosis adenitis, and 13 of M avium adenitis were identified. No FNAs were smear positive for mycobacteria. The FNA from 6/18 (33%) cases of M tuberculosis adenitis and from 4/6 (66%) M avium adenitis cases were culture positive. Bacteriological confirmation was obtained (by various methods) in 72% of tuberculous and in 100% of M avium adenitis cases. The clinical picture was different for the two organisms: tuberculous adenitis occurred mainly in caucasian adults, while M avium adenitis cases were predominantly caucasian children. None of the confirmed cases of tuberculous adenitis demonstrated drug resistance to standard anti-tuberculous agents. CONCLUSIONS: (1) Clinicians should more consistently include mycobacterial tests when investigating neck lumps. (2) FNA is not a reliable diagnostic test for mycobacterial cervical adenitis in New Zealand. Here, FNA should only be regarded as a screening test for mycobacterial adenitis. If anti-tuberculous treatment is required before it is known whether FNA has provided a positive culture, excision biopsy should first be performed to identify the mycobacterium and its susceptibility pattern.

Adult↗
PubMed1999

Evaluation of the tuberculin gamma interferon assay: potential to replace the Mantoux skin test.

We evaluated an in vitro test of cell-mediated immunity, the tuberculin gamma interferon assay, QuantiFERON-TB (QIFN), in 455 individuals from three groups: group I, 237 immigrants from high-risk countries; group II, 127 health care workers undergoing Mantoux testing; group III, 91 patients being investigated for possible active tuberculosis (79 patients) or Mycobacterium avium-Mycobacterium intracellulare complex infection (12 patients). The QIFN results were compared either to those of the Mantoux test or to microbiological and clinical diagnosis, as appropriate. In each group the correlation between the diameter of induration for the skin test and the magnitude of QIFN response was significant and of moderate strength (Spearman's rank correlation coefficient; rho = 0.59 to 0.61; P < 0.001). For group I, the agreement between QIFN and Mantoux results was 89% for Mantoux-negative and 64% for Mantoux-positive individuals. For group II, when >/=10-mm-diameter induration was taken as positive, the agreement was 81% for Mantoux-negative and 67% for Mantoux-positive individuals. For group III, agreement was 81% for Mantoux-negative and 86% for Mantoux-positive patients. For patients being evaluated for active tuberculosis, the performance of the Mantoux test was not statistically different from that of the QIFN assay. In patients with active tuberculosis, the assay had a sensitivity of 77%, not significantly higher for extrapulmonary than pulmonary cases (83% versus 74%). QIFN sensitivity was not significantly different for smear-negative or smear-positive cases (80% versus 71%). The QIFN assay is a potential replacement for the Mantoux test. The acceptability of these performance values and those of similar evaluations will determine the place this test will have in detecting evidence of mycobacterial infection.

Adolescent↗
PubMed1998

Ocular toxicity from ethambutol: a review of four cases and recommended precautions.

AIMS: To document the clinical and demographic features of cases of ethambutol ocular toxicity, to review the literature on this subject and to critically review current guidelines for ethambutol administration. METHODS: Cases of ocular toxicity from ethambutol were sought retrospectively at Green Lane and Wellington Hospitals between 1992 and 1995. The records of cases identified were examined. RESULTS: Four subjects with tuberculosis developed ocular toxicity 2 1/2, 7 1/2, 8 and 12 months after starting ethambutol. Normal visual acuity returned in three cases; one patient has severe, permanent visual impairment. Language difficulties were present in three subjects. CONCLUSIONS: Impaired communication was potentially very important in this series. Special care is needed in educating patients about ethambutol. We propose additional recommendations: 1. the usual daily dose of ethambutol should be 15 mg/kg/day, not 25 mg/kg/day; using 25 mg/kg/day (or lesser doses in the presence of renal impairment) should prompt regular formal ophthalmological evaluation (e.g. monthly) in cases with comprehension or communication difficulties; 3. both ethambutol and isoniazid should be stopped immediately if severe optic neuritis occurs. Isoniazid should be stopped if less severe optic neuritis does not improve within six weeks after stopping ethambutol.

Adult↗
PubMed1998

Automated 96-well solid phase extraction for the determination of doramectin in cattle plasma.

Automated standard and sample preparation have been coupled with 96-well solid phase extraction (SPE) technology to produce a cost effective, high throughput system for the analysis of drugs in biological media. The system was originally designed using the Packard Multiprobe 104DT robotic sample processor (RSP) to improve throughput for the assay of doramectin in cattle plasma, and the assay has since been validated (0.5-100 ng ml[-1]) using the Tecan Genesis RSP 150/8. The robotic processor conducts all liquid handling procedures involved in sample extraction. These comprise preparation of calibration standards in plasma, dispensing and diluting of plasma samples and addition of internal standard. In addition, the robot primes the 96-well SPE block, applies calibration standards and samples, draws the mixtures through the 96-well SPE block, and finally washes the block ready for manual elution. The doramectin assay involves high-performance liquid chromatography (HPLC) with fluorescence detection, and requires the sample extracts to be derivatised prior to analysis. The derivatisation procedure is performed manually in situ in the polypropylene deep 96-well block into which the samples have been eluted from the SPE-block. The derivatised samples are taken directly from the deep well block and injected into the HPLC for analysis. This type of batch processing keeps sample transfer to a minimum. Automated sample preparation, in combination with the use of 96-well technology, has reduced both cost and effort required in the analysis of doramectin in cattle plasma samples, and has resulted in improved sample throughput.

Animals↗
PubMed1997

Multidrug resistant tuberculosis in Auckland 1988-95.

AIMS: To review all cases of multidrug resistant tuberculosis (MDRTb) in Auckland between 1988-95; and to look for ways in which the diagnosis and management may be improved. METHODS: Cases of multidrug resistant tuberculosis were identified from Green Lane Hospital tuberculosis laboratory records. Clinical details were obtained from hospital case records, and radiographs were reviewed. RESULTS: Nine of the 838 (1.1%) confirmed cases of tuberculosis had multidrug resistant tuberculosis. Eight were foreign-born and four had previously been treated for tuberculosis. Three patients underwent thoracic surgery. Two patients died and one was not treated, No relapses have occurred. Potential to improve on the treatment given was evident in retrospect in three patients. CONCLUSIONS: Assessment of risk factors for multidrug resistant tuberculosis and early transfer of specimens to a tuberculosis reference laboratory are required to enable multidrug resistance to be identified early. Extensive disease, drug side effects and coexistent medical problems make MDRTb very difficult to cure. Directly observed therapy is recommended for multidrug resistant tuberculosis cases and is underutilised in Auckland.

Adult↗
PubMed1995

Role of hepatic metabolism in the bioactivation and detoxication of amodiaquine.

1. The hepatic metabolism of the antimalarial drug amodiaquine was investigated in order to gain further insight into the postulated metabolic causation of the hepatotoxicity, which restricts the use of the drug. After intraportal (i.p.) administration (54 mumol/kg) to the anaesthetized rat, the drug was excreted in bile (23 +/- 3% dose over 5 h; mean +/- SD, n = 6) primarily as thioether conjugates. 2. After i.p. administration, 20% of the dose was excreted into urine over 24 h as parent compound and products of N-dealkylation and oxidative deamination. Desethylamodiaquine accumulated in liver, but was not a substrate for bioactivation as measured by biliary elimination of a glutathione adduct. 3. Prior administration of ketoconazole, an inhibitor of P450, reduced biliary excretion by 50% and effected a corresponding decrease in the amount of drug irreversibly bound to liver proteins. This indicated a role for P450 in the bioactivation of amodiaquine to a reactive metabolite that conjugates with glutathione and protein. 4. De-ethylation and irreversible binding were observed in vitro using male rat liver microsomes, and were again inhibited by ketoconazole. However, no such binding was observed with human (six individuals) hepatic microsomes despite extensive turnover of amodiaquine to desethylamodiaquine. 5. Amodiaquine quinoneimine underwent rapid reduction in the presence of either human or rat liver microsomes. Therefore in vitro studies may underestimate the bioactivation of amodiaquine in vivo. These data indicate that the extent of protein adduct formation in the liver will depend on the relative rates of oxidation of amodiaquine and reduction of its quinoneimine. This in turn may be a predisposing factor in the idiosyncratic hepatotoxicity associated with amodiaquine. 6. Substitution of a fluorine for the phenolic hydroxyl group in amodiaquine blocked bioactivation of the drug in vivo. Insertion of an N-hydroxyethyl function enabled partial clearance of amodiaquine and its deshydroxyfluoro analogue via O-glucuronidation and altered the balance between phase I oxidation and direct phase II conjugation of amodiaquine.

Amodiaquine↗
PubMed1994

The effect of fluorine substitution on the metabolism and antimalarial activity of amodiaquine.

Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial which causes adverse side effects such as agranulocytosis and liver damage. The observed drug toxicity is believed to be related to the formation of an electrophilic metabolite, amodiaquine quinone imine (AQQI), which can bind to cellular macro-molecules and initiate hypersensitivity reactions. 5'-Fluoroamodiaquine (5'-FAQ, 3), 5',6'-difluoroamodiaquine (5',6'-DIFAQ,4), 2',6'-difluoroamodiaquine (2',6'-DIFAQ,5), 2',5',6'-trifluoroamodiaquine (2',5',6'-TRIFAQ, 6) and 4'-dehydroxy-4'-fluoroamodiaquine (4'-deOH-4'-FAQ,7) have been synthesized to assess the effect of fluorine substitution on the oxidation potential, metabolism, and in vitro antimalarial activity of amodiaquine. The oxidation potentials were measured by cyclic voltammetry, and it was observed that substitution at the 2',6'- and the 4'-positions (2',6'-DIFAQ and 4'-deOH-4'-FAQ) produced analogues with significantly higher oxidation potentials than the parent drug. Fluorine substitution at the 2',6'-positions and the 4'-position also produced analogues that were more resistant to bioactivation. Thus 2',6'-DIFAQ and 4'-deOH-4'-FAQ produced thioether conjugates corresponding to 2.17% (SD: +/- 0.27%) and 0% of the dose compared with 11.87% (SD: +/- 1.31%) of the dose for amodiaquine. In general the fluorinated analogues had similar in vitro antimalarial activity to amodiaquine against the chloroquine resistant K1 strain of Plasmodium falciparum and the chloroquine sensitive T9-96 strain of P. falciparum with the notable exception of 2',5',6'-TRIFAQ (6). The data presented indicate that fluorine substitution at the 2',6'-positions and replacement of the 4'-hydroxyl of amodiaquine with fluorine produces analogues (5 and 7) that maintain antimalarial efficacy in vitro and are more resistant to oxidation and hence less likely to form toxic quinone imine metabolites in vivo.

Amodiaquine↗
PubMed1992

Intermittent supervised treatment of tuberculosis at Green Lane Hospital, 1987-8.

AIMS: to assess the results of the first two years experience with intermittent supervised treatment of tuberculosis (IST) in Auckland, looking especially at practical problems. METHOD: the hospital records of the 16 patients who received IST during 1987-8 were reviewed retrospectively, and public health nurses who administered the medications were questioned about problems that were encountered. RESULTS: two-thirds of those who were given IST were Polynesian. In retrospect, the need for IST could have been anticipated in eight of the 12 patients (67%) who failed to comply with daily treatment. Five of the 16 IST patients presented major problems to the nurses supervising the twice weekly treatment. Poor motivation, itinerancy and alcohol abuse were the most common factors causing difficulty. IST was successfully completed in 13/16 patients (81%) and was abandoned in only one patient. Only two patients completed IST with a drug regimen for resistant organisms. Health nurse supervision resulted in improvements in understanding and attitude to tuberculosis, eventually enabling two patients to self medicate without supervision. CONCLUSIONS: IST is a practical treatment method in New Zealand, permitting curative therapy in a group of tuberculosis patients who would otherwise create risks of drug resistance, disease reactivation and spreading the disease.

Adult↗
PubMed1992

The mechanism of bioactivation and antigen formation of amodiaquine in the rat.

A glutathione conjugate of amodiaquine has been isolated and characterized from rat bile after administration of [14C]amodiaquine (50 mumol/kg, 5.0 muCi/rat) to anaesthetized male Wistar rats. Thioether conjugates of amodiaquine in rat bile accounted for a total of 12% of the dose, 5 hr after administration of the drug. In addition, 1% of the dose remained in the liver covalently bound to tissue proteins after 5 hr. These findings provide direct evidence that a chemically reactive metabolite, amodiaquine quinoneimine, has been formed from the drug in vivo. A second major metabolite, desethylamodiaquine, accounting for 14% of the given dose, was present in the liver after 5 hr. Enzyme inhibition studies with ketoconazole-pretreated rats showed that both amodiaquine quinoneimine and desethylamodiaquine formation can be catalysed by cytochrome P450. The demonstration that amodiaquine readily and extensively forms a metabolite in vivo, with strong reactivity towards protein and non-protein thiol groups, may help to explain the idiosyncratic toxicity observed in man.

Amodiaquine↗
PubMed1991

Pneumocystis carinii pneumonia as a complication of methotrexate treatment of asthma.

A 32 year old man with chronic severe asthma, requiring maintenance oral corticosteroids, was started on a weekly dose of methotrexate. Eleven weeks later he developed Pneumocystis carinii pneumonia. In the two years following treatment there has been no recurrence while oral corticosteroid treatment has been continued. Pneumocystis pneumonia should be considered in asthmatic patients taking methotrexate who present with fever, pulmonary infiltrates, and hypoxia.

Adult↗
PubMed1991

Effects of water immersion on cardiac output of lean and fat male subjects at rest and during exercise.

To investigate the combined effect of water immersion (WI) and lean body mass on cardiac output (Q), 12 healthy young men, 6 lean (fat less than 9%) and 6 fat (fat greater than 18%), were studied at rest and during steady state exercise approximating 30-40% Vo2 max under three experimental conditions. There were on land at 24 degrees C (LND), and immersed in water at 33-34 degrees C to hip level (HIP), and to the xiphoid (XIP). Metabolic measures were determined during 30-s periods from the average breath measurements. Mixed venous PCO2 (PVCO2) was estimated using rebreathing equilibration technique. Cardiac output was calculated by the indirect Fick's principle. In the lean individuals the average Q rose from a resting value of 5.43 +/- 0.43 (LND) to an exercise value of 7.25 +/- 0.40 L/min (XIP), and from resting value of 5.62 +/- 0.40 to an exercise 6.47 +/- 0.5 L/min in the fat individuals. During exercise, the associated increase in Q with increasing WI was significantly (p less than 0.05) higher compared with the land experiments. Inspection of the mean profile corresponding to this increase indicated that an increase in the level of immersion results in a significant (p less than 0.05) increase in the average Q for the lean group. For the fat group, the average Q was significantly (p less than 0.05) larger only at XIP level. At rest, heart rate dropped from 67 +/- 3.36 (LND) to 60 +/- 4.13 (XIP), and from 79 +/- 3.73 to 73 +/- 4.10 BPM for the lean and fat group, respectively. MANOVA analysis showed a significant (p less than 0.05) interaction between WI and group membership, indicating that the effect of WI is significantly different between the two groups. These data indicate that the change in central blood volume with WI depends, in part, on the lean mass of the body.

Adult↗
PubMed1990

The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms.

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.

Asthma↗