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Biomedical subjects

N Tong

Publications and source records attributed to N Tong.

33 records · Page 2Linked to original sources
PubMed1995

Identification of the sites for suppressor mutations on the hemagglutinin molecule to temperature-sensitive phenotype of the influenza virus.

A temperature-sensitive (ts) mutant of the influenza virus A/WSN/33 strain, ts-134, possessed a defect in intracellular transport at the nonpermissive temperature and marked thermolability of hemagglutinin (HA) activity at 51 C. These were caused by a change at amino acid residue 157 from tyrosine to histidine in the HA protein. We isolated 37 spontaneous revertant clones from ts-134 at the nonpermissive temperature and determined their HA sequences. The deduced amino acid sequences demonstrated that one was a true revertant and the others were revertants with suppressor mutations, each of which had an additional amino acid change besides those of ts-134. The changed amino acids were located at 14 positions on the HA molecule, and eight of them were found in multiple revertants. These were located in five to six distinct regions on the three-dimensional structure of the HA molecule. However, the heat stability of HAs in the revertants was recovered differently depending on the sites of the changed amino acids. The kinetics of transport of the HA protein in the revertants were slightly delayed compared to the wild-type both at permissive and nonpermissive temperatures.

Animals↗
PubMed1992

Prospective audit of an aminoglycoside consultative service in a general hospital.

OBJECTIVE: To investigate the impact of the introduction of a consultative service on the use, efficiency of dosing and clinical toxicology of the aminoglycoside antibiotics, gentamicin and tobramycin, in a general hospital. METHODS: Two audits were conducted six months and 18 months after the introduction of the consultative service. The audits reviewed the use of drug assay services, the adequacy of drug administration (as measured by serum antibiotic concentrations), indications for prescription, adverse outcomes (by noting markers of nephrotoxicity) and the antibiotic sensitivity of Gram-negative pathogens. The results were compared with the results of an audit conducted before the consultative service was instituted. RESULTS: There was a significant (P < 0.001 by chi 2 test) increase in the use of assays, with drug assays performed in 67% (first audit) and 77% (second audit) of aminoglycoside courses compared with 48.2% in the pre-intervention audit. Sample timing was greatly improved, with more than 70% of the samples collected at the appropriate times. Assay wastage in terms of uninterpretable assay results decreased significantly (P < 0.001) from 42.9% of total assays to 6.3% at the first audit and 3.8% at the second audit. The percentage of assay results in the desirable range increased significantly (P < 0.001) from 39.1% to 71.9% (first audit) and 75.4% (second audit). Pharmacokinetic recommendations were made in 39.1% and 64% of all aminoglycoside courses during the first and second audits respectively, with clinician acceptance of dosage recommendations at 83.1% and 82.8% respectively. For aminoglycoside courses prescribed for therapeutic reasons, 97.9% (first audit, n = 325) and 98.6% (second audit, n = 280) of indications for use were judged as clinically appropriate. The incidence of suspected aminoglycoside-induced nephrotoxicity was reduced from 8.9% of patients to 1.6% (first audit, P < 0.001) and 2.4% (second audit). Bacterial sensitivity audits showed that the great majority of clinical isolates of target organisms (n = 3523, Year 1 and n = 3385, Year 2) were sensitive to gentamicin (92.2% and 91.5% respectively) and tobramycin (98.1% and 98.8% respectively); these aminoglycosides exceeded all alternative agents in effectiveness, including first and third generation cephalosporins. CONCLUSIONS: The overall results indicate that introduction of the consultative service had a positive impact on the effective use of aminoglycosides, with a marked decrease in clinical toxicity. These influences were shown to persist for at least 18 months. The availability of reliable predictive techniques to reduce toxicity allows active promotion of aminoglycosides as the agents of choice on grounds of efficacy and economy.

Blood Specimen Collection↗
PubMed1991

Dosage adjustment and clinical outcomes of long-term use of high-dose tobramycin in adult cystic fibrosis patients.

A two-phase study was undertaken designed to investigate the impact of computer-aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis. In phase one, a baseline (historical control) study of drug use patterns was performed. During the second phase, patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were randomly allocated to one of two schedules. Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocols using serum tobramycin assay data determined three times weekly. Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population-based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression. The agreed therapeutic target was a peak serum tobramycin concentration of 8-10 mg/L and a trough concentration of 1-2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges (group A-14%; group B-34.7%, chi 2 test, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[The effect of gemfibrozil on serum apo C II and C III in diabetic hyperlipidemia].

The effects of gemfibrozil on apolipoproteins C II and C III (apo C II, C III) were observed in 20 NIDDM hyperlipidemic patients. All of the patients continued their anti-diabetic treatment, gemfibrozil 900 mg/day for 4 weeks. The results revealed no significant change in fasting plasma glucose (FPG) and HbA1 before and after the study. But after the treatment with gemfibrozil, the following parameters changed significantly: total cholesterol (TC) decreased by 18.64% (P less than 0.01), total triglyceride (TG) decreased by 65.05% (P less than 0.001), VLDL-C decreased by 63.19% (P less than 0.001), HDL-C increased by 44.23% (P less than 0.001), apo C III decreased by 31.38% (P less than 0.02), and the ratio of apo C III/C II reduced by 35.49% (P less than 0.01). These findings suggest that gemfibrozil has excellent effect on decreasing apo C III and the ratio of apo C III/C II, thus facilitates the metabolism of chylomicron and decreases TG level in hyperlipidemic diabetic patients.

Aged↗
PubMed1989

Prospective audit of aminoglycoside usage in a general hospital with assessments of clinical processes and adverse clinical outcomes.

A comprehensive, multiphasic review of gentamicin and tobramycin utilization was undertaken with audits of the microbiological sensitivity of Gram-negative pathogens; indications for the prescription of aminoglycoside agents; the utilization of assay services; the adequacy of clinical drug delivery by measures of serum antibiotic levels; and the assessment of adverse outcomes by markers of nephrotoxicity. The great majority of clinical isolates of target organisms (n = 4208) was more sensitive to gentamicin (96%) and to tobramycin (99%) than to all alternative agents, including first- and third-generation cephalosporin agents. A review of the indications for the prescription of aminoglycoside agents by clinical criteria showed that in 85.6% of 278 documented cases, the choice of agent was appropriate by clinical and microbiological criteria. In a substantial (77.6%) proportion of the 511 patients who were receiving therapeutic courses of an aminoglycoside agent, serum drug assays had been performed. Assay data could not be interpreted adequately in 52.6% of 3079 assayed cases as a result of inadequate data on administration regimens (39.7%) or sampling regimens (12.9%). Where sampling was documented adequately, there was extreme variation (zero to five hours) in post-dose sampling. In only 33.2% of cases could it be concluded unambiguously that the patients were receiving safer, adequate therapy for clinically significant infections, 5.6% of patients were receiving potentially toxic doses, and 8.6% of patients showed suboptimal concentration profiles. The majority of potentially toxic levels were associated with adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗
PubMed1986

Polypharmacy in an Australian teaching hospital. Preliminary analysis of prevalence, types of drugs and associations.

A computer-based prescription retrieval system was used to study 21,521 prescriptions that had been provided to hospital patients who were receiving predominantly outpatient care. Over a three-month period 338 patients were found to be receiving 10 or more different drugs concomitantly. A further 338 patients were drawn at random from the same outpatient population for comparison. Age was linked significantly to polypharmacy (polypharmacy group: mean age, 63.7 years, SEM = 1.09; comparison group: mean age, 53.8 years, SEM = 1.00, P less than 0.05; chi 2 = 62.8, P less than 0.001). The relative risk of polypharmacy was related linearly to age. Admission to hospital was associated with increased prescribing rates in the polypharmacy sample (P less than 0.05), as was attendance at multiple clinics and multiple attendance at outpatient clinics (P less than 0.05 and P less than 0.05, respectively). Benzodiazepine agents were included in 63.7% of prescriptions in the polypharmacy group and in 37.3% of prescriptions in the comparison group. Non-prescription drugs were noted in 97.2% of prescriptions in the polypharmacy group and 58.0% of prescriptions in the comparison group, representing 34.7% and 27.3% of all items, respectively. In patients of less than 30 years of age agents for allergy/asthma/atopy contributed most to polypharmacy; agents that were associated with renal failure most in patients aged 31-50 years; and agents for cardiovascular disease contributed most in patients aged over 50 years. Our results suggest that a reduction in the use of non-prescription and psychotropic agents, heightened awareness of the dangers of polypharmacy and coordination and integration of over-all care and prescribing habits should reduce polypharmacy materially.

Australia↗
PubMed1985

Availability of drug assay results and dosage advice improves antiepileptic care in a specialist neurology outpatient clinic.

The incidence of grand mal seizures, distribution of drug levels relative to the therapeutic range and the incidence of side effects were monitored before and after the provision of same-day preconsultation assay results (phenytoin and carbamazepine) to an epilepsy clinic. A total of 300 patients completed the study. The proportion of patients fitting fell from 23.3% at entry to 10% at review (P less than 0.01) while the incidence of side effects fell from 30.7% to 17.3% (P less than 0.01) and the proportion of phenytoin levels in the therapeutic range rose from 41% to 58% (P less than 0.01). Similar patterns were observed in 111 patients who entered the study during a control observation period. The provision of appropriate support services (assay results and dosage advice) to specialist epilepsy clinics allows improvement in the management of epilepsy.

Adolescent↗
PubMed1984

Computer-based prescription audit as a research, educational and management tool.

An existing dedicated pharmacy computer system (MIDAS system, Alfred Hospital and Health Computing Services, Victoria) used primarily for pharmacy labelling and dispensing, has been rewritten for an in-house minicomputer, with enhancements that allow it to be used in budgetary predictions, drug use monitoring, therapeutic audit and as a research tool. An automatically updated hard copy record of individual patient prescription profiles is generated and represents a valuable addition to the patient medical record. Allied to automatic "sorting" and retrieval techniques, all patients on nominated drugs can be identified and their records examined for particular combination use. Current application to assessment of nifedipine- beta blocker use will be presented, as will an application to cimetidine audit. Prescriptions can be scanned and segregated in terms of numbers of prescriptions in addition to segregation in terms of a particular therapeutic agent. Initial application to audit has detected an unacceptable level of polypharmacy (more than 26% of all prescriptions involve greater than or equal to 5 items and more than 3% involved greater than or equal to 10 items). Statistical information on the volume and unit cost of outpatient prescribing allows a precise estimate of ongoing budgetary commitments, while trends in discharge medication profiles allow a basis for prediction of budgetary trends, particularly with respect to the use of recent additions to the formulary. The system allows for expansion at minimal cost with potentially revolutionary applications, for example, interactive prescriber education if and when "on-line" capabilities are developed. Cross-linking with relevant data-bases will allow a major expansion of applied research into therapeutic drug use and its consequences.

Australia↗
PubMed1983

Successful substitution of rectal metronidazole administration for intravenous use.

Wound infection and isolation of anaerobic organisms before and after intravenous and rectal administration of metronidazole were studied in 24 505 surgical patients. In the 6303 patients who underwent "risk" surgery (bowel, biliary, gynaecological, or otolaryngological surgery) introduction of intravenous metronidazole was associated with a striking fall in wound infection and wound anaerobe isolation rates; and the changes were maintained when the majority of metronidazole used was in suppository form. In the 18 202 patients who underwent "clean" surgery (e.g., orthopaedic, ophthalmic, and plastic surgery) metronidazole use was associated with a small formulation-independent change in infection rate without change in anaerobe isolation rates. Without compromising clinical care the use of intravenous metronidazole can be limited to a minority of patients with special needs.

Anaerobiosis↗
PubMed1983

Doxorubicin-associated delayed ventricular fibrillation in acute promyelocytic leukemia.

A 16-year-old schoolgirl presented with acute promyelocytic leukemia. 10 days after induction chemotherapy with doxorubicin and cytosine arabinoside together with heparinisation for the accompanying disseminated intravascular coagulopathy, she developed ventricular fibrillation. Following successful cardiac resuscitation a gated blood pool scan showed a left ventricular ejection fraction of 49%. Despite this event the patient was subsequently rechallenged with doxorubicin without any adverse cardiac effect. The exact mechanism for this delayed doxorubicin-associated cardiac arrhythmia is not clear, but electrolyte disturbance and heparin-doxorubicin interaction may have played a contributory role.

Adolescent↗