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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Quantitative analysis of sirolimus (Rapamycin) in blood by high-performance liquid chromatography-electrospray tandem mass spectrometry.

We report here a quantitative method for the analysis of sirolimus in blood using solid-phase sample preparation and HPLC-electrospray-tandem mass spectrometry detection. Blood samples (500 microl) were prepared by pre-treatment with acetonitrile: 15 mM zinc sulphate (70:30, v/v), containing 32-demethoxysirolimus (internal standard) and C18 solid-phase extraction. The electrospray conditions were chosen to enhance the [M+NH4]+ species at the expense of other species. Detection was by multiple reactant monitoring with the mass transitions m/z 931.8-->864.6 and m/z 901.8-->834.4 employed for sirolimus and the internal standard, respectively. The method was linear over the range 0.2 to 100.0 microg l(-1). The accuracy and inter-day precision, over this concentration range, was 94.4% to 104.4% and 1.4% to 5.0%, respectively. The accuracy and total precision at the limit of quantitation (0.2 microg l(-1)) was 103.0% and 10.8%, respectively. The mean absolute recovery of sirolimus and the internal standard were 80.5% and 81.3%, respectively. The sensitivity and analytical concentration range of the method make it suitable for therapeutic drug monitoring and pharmacokinetic studies. Further, the ability of the method to measure parent drug specifically will facilitate the evaluation of immunoassays for sirolimus.

Anti-Bacterial Agents↗
PubMed1998

High-performance liquid chromatography determination of mycophenolic acid and its glucuronide metabolite in human plasma.

Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid (MPA) and the other is a simultaneous assay for MPA and its metabolite mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500 microl) with added internal standard were acidified and extracted using C18 solid-phase extraction cartridges. Chromatographic separation was achieved on a C18 Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and 2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%. These methods are suitable for therapeutic drug monitoring and pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed1998

Microscale high-performance liquid chromatography-electrospray tandem mass spectrometry assay for cyclosporin A in blood.

To facilitate quantitative analysis of cyclosporin A in low volume blood samples we developed a sensitive and specific microscale reversed-phase HPLC-electrospray tandem mass spectrometry assay. Blood samples (100 microl) were prepared by acetonitrile precipitation and C18 solid-phase extraction. Detection was by multiple-reactant monitoring. The method was linear over the range 5-1000 microg/l (r> or =0.997) with accuracy between 95.4 and 102.0% over this range. Total imprecision was 11.1% at 10 microg/l and 2.8% at 800 microg/l. Absolute recovery of cyclosporin A and internal standard was 72.5 and 73.3%, respectively. When this method was evaluated against a conventional HPLC with UV detection, in patient samples, they were interchangeable (y=0.988x + 10.0, r=0.996). This HPLC-ESI-MS-MS method will be applicable to therapeutic monitoring in paediatric transplant patients and multiple point pharmacokinetic studies in animals and humans.

Chromatography, High Pressure Liquid↗
PubMed1998

Hirschsprung's disease: genetic and functional associations of Down's and Waardenburg syndromes.

Despite significant advances in understanding the genetic background in Hirschsprung's disease (HD), the majority of cases are believed to be multigenic and multifactorial. Conditions associated with an increased risk of HD suggest some common inherited factor and include Down's syndrome, Waardenburg syndrome (WS), dominant sensorineural deafness, neurofibromatosis, neuroblastoma, phaechromocytoma, the MEN type 2B syndrome, and other abnormalities. The reported incidence of Down's syndrome in HD is approximately 2%, but the range varies from 2% to 15%. WS, on the other hand, is one of a number of uncommon human conditions in which pigmentary disturbances are associated with sensorineural deafness. HD mutations have been mapped to a number of genes, i.e., RET proto-oncogene, at 10q11.2; the recessive EDNRB gene, located at 13q22; its ligand endothelin 3 (EDN3); and the glial cell line-derived neurotrophic factor (GDNF) in humans. Mutations of known genes appear to account for only a relatively small number of HD cases (20% in the case of RET). GDNF may modulate the disease phenotype by interacting with other susceptibility loci (e.g., RET). The genetic aspects of HD occurring in association with trisomy 21 and WS are reviewed. Clinical presentation, diagnosis, treatment and long-term outcome in this patient group are evaluated. Additional data are presented on 12 children with Down's syndrome out of 408 surgically treated HD patients. The role of associated anomalies is evaluated, and an increased susceptibility to severe enterocolitis associated with a high mortality rate is reported. Surgical correction can be achieved, but patients may require some form of ongoing help to facilitate acceptable bowel function. The decision as to the nature and timing of the surgical correction must be individualized.

Down Syndrome↗
PubMed1998

Current surgical practice in screening for colorectal cancer based on family history criteria.

BACKGROUND: As awareness about colorectal cancer increases there has been a steady rise in the number of referrals of relatives of patients with colorectal cancer to colorectal surgeons for screening investigations based on family history criteria. Surgeons are generally not trained in either risk assessment of inherited colorectal cancer or genetic counselling. As this is a relatively new area of service, there is likely to be variation in the management of these individuals. METHODS: This study investigated the family history criteria used and the colonic screening practices employed by a group of consultant colorectal surgeons by means of a postal questionnaire distributed and collected through their specialist association. RESULTS: The results show not only wide variation in the practice of colorectal screening based on family history criteria, but also a considerable waste of resources in the provision of illogical and inappropriate investigations. CONCLUSION: Given the lack of evidence on which to base this clinical practice and the current financial difficulties in the health service, the authors question whether it is appropriate for surgeons to continue to provide such a service.

Adult↗
PubMed1998

A randomized, prospective, blinded comparison of postoperative pain, metabolic response, and perceived health after laparoscopic and small incision cholecystectomy.

BACKGROUND: We have previously shown that in a randomized comparison of laparoscopic (LC) versus small incision (SC) cholecystectomy, postoperative hospital stay is comparable. This randomized prospective study compares the postoperative pain, analgesic and antiemetic consumption, perceived health, and metabolic and respiratory responses after these two procedures. METHODS: Two hundred patients were recruited; postoperative stay, pain scores, analgesic and antiemetic consumption were recorded. Nottingham Health Profile questionnaires were completed by a subgroup of 100 patients, and the metabolic and respiratory responses were also compared in a further subgroup of 20 patients. RESULTS: Pain scores in both groups were low. LC, however, was associated with lower postoperative pain scores and analgesic requirements compared with SC, but the antiemetic requirements were greater after LC. The duration of hospital stay and the perceived health after operation were the same in both groups, and both procedures were associated with a similar reduction of respiratory function. Twenty-four hours after operation the inflammatory (C-reactive protein, CRP) response to LC (22 +/- 20 mg/L) was significantly lower than after SC (68 +/- 30 mg/L), but the neuroendocrine (cortisol) response was similar (LC, 475 +/- 335 nmol/L, compared with SC, 710 +/- 410 nmol/L). Independent of the technique used, the duration of postoperative hospital stay correlated significantly with the magnitude of both the 24-hour postoperative cortisol and CRP responses (cortisol: rs = 0.678, p < 0.001; CRP: rs = 0.566, p = 0.011). CONCLUSIONS: LC appears to be associated with less tissue destruction and pain than SC, but this did not confer any advantage in the degree of postoperative respiratory impairment, length of hospital stay, or postoperative perceived health. The neuroendocrine component of the metabolic response evoked by each procedure was similar and had a significant correlation to patient's postoperative hospital stay. This finding may explain the similar postoperative recovery after LC and SC.

Adult↗
PubMed1998

Plasma indomethacin assay using high-performance liquid chromatography-electrospray-tandem mass spectrometry: application to therapeutic drug monitoring and pharmacokinetic studies.

The authors report the use of high-performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantification of indomethacin (IND) in plasma with microscale sample preparation. Plasma samples (100 microL) and mefanamic acid (internal standard [IS]), buffered to pH 3.5, were prepared using solid phase extraction and chromatographed using a C8 column. The mobile phase composition was 80% methanol to 20% ammonium acetate buffer (40 mM, pH 5.1). A flow rate of 300 microL per minute was used with a 1-to-12 postcolumn split into the mass spectrometer. Selected reaction monitoring with mass transitions m/z 357.9-->139.0 and m/z 242-->209.0 were used for IND and IS, respectively. The chromatographic analysis time was 4 minutes. The assay was linear from 5 microg/L to 2000 microg/L with interday imprecision (n=5) over the analytic range (5%). At four concentrations (10 microg/L, 25 microg/L, 250 microg/L, 1500 microg/L), assay imprecision was 9% (total coefficient of variation [CV]) and accuracy ranged between 96.5% and 102.8% (n=16). The absolute recovery of IND and IS was 74% (n=8) and 95% (n=24), respectively. This method was developed and validated in less than 10 working days, had a lower limit of quantification than reported HPLC-ultraviolet (UV) methods, and uses small sample volumes. These factors illustrate the power of HPLC-ESI-MS/MS for drug analysis. Furthermore, the ability of this method to measure IND over a wide concentration range makes it suitable for therapeutic drug monitoring and pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed1998

A requiem for the cholecystokinin provocation test?

BACKGROUND: The cholecystokinin provocation test (CCKPT) has been claimed to predict a better symptomatic result after cholecystectomy in patients with acalculous biliary pain. AIMS: To examine the predictive value of the CCKPT for symptom relief after cholecystectomy in both CCKPT positive and negative patients. PATIENTS AND METHODS: Fifty eight patients with acalculous biliary pain underwent CCKPT with serial ultrasound gall bladder volumetry. CCKPT positive patients were offered cholecystectomy; negative patients were reassessed and were offered a cholecystectomy if symptoms persisted. Six months after cholecystectomy, the CCKPT was repeated. RESULTS: Of 32 CCKPT positive patients, 27 underwent cholecystectomy and of these, 18 (67%) became symptom-free. Postoperatively, 20 of 25 patients converted to CCKPT negative but five remained CCKPT positive and were symptomatic. Of the 26 CCKPT negative patients, nine became symptom-free without cholecystectomy; six of 14 (42.8%) patients undergoing cholecystectomy became asymptomatic and remained CCKPT negative. Cholecystectomy seemed to reduce symptoms in both groups, but there was no significant difference in the symptomatic outcome between preoperative CCKPT positive and negative patients. CONCLUSIONS: In this study, cholecystokinin provocation testing did not predict symptomatic benefit from cholecystectomy and we suggest it should no longer be used in the evaluation of patients with acalculous biliary pain.

Adolescent↗
PubMed1998

The epidemiology of Parkinson's disease in an Australian population.

A prevalence study of Parkinson's disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53-775). We performed a separate case-control study involving 224 patients with PD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family hisotry. This demonstrates the need for improved understanding of the genetic nature of the disease.

Age of Onset↗
PubMed1998

Giant hydronephrosis--a diagnostic dilemma.

We report a complex case in which the left kidney had undergone giant hydronephrotic change after chronic obstruction at the vesicoureteric junction. Minor blunt abdominal trauma caused rupture of the parenchyma of this expanded and dilated kidney, with bleeding into its collecting system. The mixture of blood and urine remained contained within the kidney's structural layers, so producing a tense, cystic, fluid-filled mass arising from the left hypochondrium. Pathogenesis, differential diagnosis and investigation of giant hydronephrosis and its rupture are discussed. The observation is made that gross distortion of the renal parenchyma by rupture or hydronephrosis impairs arterial inflow to the kidney.

Abdominal Injuries↗
PubMed1998

NSAIDs and blood pressure. Clinical importance for older patients.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive medication increases with age to 26% and > 50%, respectively, among the elderly. Overall, 12 to 15% of elderly individuals take at least 1 NSAID and an antihypertensive medication concurrently. A large case-control study of older individuals demonstrated that recent users of NSAIDs had a 1.7-fold increase in risk of initiating antihypertensive therapy compared with non-users. A community-based epidemiological study revealed that NSAID use significantly predicted the presence of hypertension (odds ratio 1.4, 95% confidence interval 1.1 to 1.7) in the elderly. Furthermore, among those taking antihypertensive agents in the 65+ Rural Health Study, in Iowa, US, individuals also taking NSAIDs had a mean systolic blood pressure (BP) 4.9 mm Hg higher than non-users of NSAIDs. The hypertensive effect of NSAIDs varies depending on the specific NSAID used and the type of antihypertensive agent, if they are taken concurrently. While the results of randomised, controlled trials in the elderly have been conflicting, 2 meta-analyses involving younger adults have revealed that NSAID use produces a clinically significant increment in mean BP of 5.0 mm Hg, which is most marked in patients with controlled hypertension. Stratification by NSAID type has revealed that piroxicam and indomethacin had the greatest, and sulindac the least, pressor effect. While the mechanisms) of the pressor effect remain speculative, salt and water retention, caused by several factors operating in parallel, coupled with an increased total peripheral vascular resistance via increased renal endothelin-1 synthesis, are potentially important. A 5 to 6 mm Hg increase in diastolic BP maintained over a few years may be associated with a 67% increase in total stroke occurrence and a 15% increase in events associated with coronary heart disease. Clinicians should strive to avoid excessive use of NSAID treatment and consider alternative, well-tolerated therapeutic options, including simple analgesics and physical therapy. For patients who require concomitant NSAID and antihypertensive treatment, clinicians should be aware of the greater hypertensive effect of indomethacin and piroxicam compared with alternative NSAIDs, and the potential for relatively greater antagonism by NSAIDs of the BP-lowering effect of beta-blockers compared with other antihypertensives. Finally, the progress of each patient should be monitored by careful BP measurement particularly during the initiation of NSAID therapy.

Aged↗
PubMed1998

Is it necessary to catheterise the bladder before laparoscopy?

Fifty patients had residual urine measured by catheterisation immediately before laparoscopic cholecystectomy. The median amount of urine in the bladder was 100 ml (range 5-500 ml). This urine volume does not distend the bladder enough to risk inadvertant perforation during insertion of a subumbilical port. Urinary bladder catheterisation is unnecessary before laparoscopy especially if the bladder is impalpable.

Adult↗