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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evaluation of the tacrolimus II microparticle enzyme immunoassay (MEIA II) in liver and renal transplant recipients.

We evaluated the MEIA II with blood samples with added tacrolimus (3.0, 5.0, 11.0, and 22.0 microg/L). The assay had acceptable recoveries (99-103%) and intraday imprecision (<16.0%) across the range of concentrations studied, except for the recoveries at 3.0 microg/L (86.3%) and 5.0 microg/L (80.7%). Comparison of liver (n = 116) and renal (n = 113) patient samples measured by MEIA II against HPLC-tandem mass spectrometry (HPLC-MS/MS) found a mean overestimation of 15.6%. From these comparison data it can be calculated that at values of 5 and 20 microLg/L in liver or renal transplant patient samples, measured by HPLC-MS/MS, MEIA II will have the corresponding range estimates of 3.6-7.9 microg/L and 20.9-25.4 microg/L, respectively. No clinically significant difference in results, in terms of overestimation or correlation, was observed between the two transplant groups studied. The MEIA II is an improvement on the previous MEIA I and is suitable for the therapeutic drug monitoring of tacrolimus where HPLC-MS/MS is unavailable.

Chromatography, High Pressure Liquid↗
PubMed1997

A reference method for the analysis of aldosterone in blood by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

A high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS/MS) reference method for the quantitation of aldosterone in serum and plasma has been developed. Samples were extracted with dichloromethane/diethyl ether, containing flumethasone as internal standard (IS). Chromatography was performed on a phenyl column using 50 mm ammonium formate (pH 7.1)/methanol (50/50, v/v) as mobile phase. Analysis was in negative-ionization mode by selected reaction monitoring (aldosterone m/z 359.2 --> 331.2; IS m/z 455.0 --> 379.0). The assay was linear over the range 15-500 pg/mL, with limits of detection and quantitation of 10 and 15 pg/mL, respectively. Imprecisions of the assay at 15, 20, 150, and 450 pg/mL were 18.5, 8. 8, 10.6, and 9.5%, respectively. The accuracy of the method ranged from 93.1 to 98.9% with absolute recoveries between 84.0 and 91.3% (aldosterone) and 88.0 and 92.3% (IS). We present a case study of a patient admitted, with suspected primary hyperaldosteronism, on the basis of a high radioimmunoassay (RIA) aldosterone concentration. The results suggest that RIA was unreliable, causing unnecessary patient discomfort and a costly 6-day hospital stay. The specific HPLC-API-MS/MS assay described offers the sensitivity and accuracy required to assess abnormal aldosterone production in hypertensive patients.

Aldosterone↗
PubMed1997

Chemical ablation of the gallbladder.

BACKGROUND: Chemical ablation of the gallbladder might avoid the need for surgery in elderly, unfit patients. This study examined the efficacy of various chemicals in destroying gallbladder mucosa. METHODS: Ninety-five per cent ethanol, 3 per cent sodium tetradecyl sulphate (STD), trifluoroacetic acid (TFA) 2 mol/l, tetracycline 50 mg/ml, 30 and 50 per cent phenol, and a mucosal exfoliant solution (compound ethylene diamine tetra-acetic acid) were tested for gallbladder ablation in rabbits. Histology was obtained 8 weeks after exposure to these chemicals. RESULTS: Thirty per cent phenol, tetracycline, TFA and ethanol when used as single agents were moderately effective in causing complete gallbladder mucosal obliteration, 50 per cent phenol caused a macroscopic burn of the entire gallbladder. The mucosal exfoliant solution and STD on their own did not cause mucosal destruction but had significantly enhanced efficacy when combined with 95 per cent ethanol, allowing reliable mucosal destruction with a 5-min contact duration. CONCLUSION: Ninety-five per cent ethanol and STD after pretreatment with a mucosal exfoliant solution may be the combination of choice for in situ gallbladder mucosal ablation.

Animals↗
PubMed1997

NSAIDs and increased blood pressure. What is the clinical significance?

Several randomised studies have demonstrated that various nonsteroidal anti-inflammatory drugs (NSAIDs) elevate blood pressure in normotensive and hypertensive individuals; however, these data have been contradicted by numerous negative studies. Two meta-analyses have demonstrated that, after pooling data drawn from published reports of randomised trials of younger adults, NSAID use produces a clinically significant increment in mean blood pressure of 5 mm Hg, most marked in patients with controlled hypertension. Stratification by NSAID type revealed that piroxicam, naproxen and indomethacin had the greatest, and sulindac the smallest, pressor effect. These data were supported by 2 large community studies involving elderly patients. Recent NSAID users had a 1.7-fold higher risk of requiring the initiation of antihypertensive therapy compared with nonusers; NSAID users also had a 40% increased risk of receiving a diagnosis of hypertension compared with nonusers. It is vital to determine the nature of the association in the elderly, 12 to 15% of whom are concurrently receiving an NSAID and an antihypertensive agent. Importantly, a 5 to 6 mm Hg increase in diastolic blood pressure maintained over a few years may be associated with a 67% increase in total stroke risk and a 15% increase in coronary heart disease events. While the mechanism(s) remain speculative, salt and water retention through several factors operating in parallel, coupled with increased total peripheral vascular resistance, via increased renal endothelin-1 synthesis, are potentially important. Clinicians should strive to avoid excessive use of NSAID treatment and consider well-tolerated therapeutic alternatives, including simple analgesics and physical therapy. For patients who require concomitant NSAID and antihypertensive treatment, physicians should be aware that indomethacin, naproxen and piroxicam may be associated with a greater pressor effect than many other NSAIDs, and that antagonism of beta-blockers may be greater than that of vasodilators (including ACE inhibitors and calcium antagonists) and diuretics. Finally, the progress of each patient should be monitored by careful blood pressure measurement, particularly during the period of initiation of NSAID therapy.

Adult↗
PubMed1997

Gallstone removal with a modified cholecystoscope: an alternative to cholecystectomy in the high-risk patient.

BACKGROUND: Symptomatic gallstones in patients who are at high risk from or who wish to avoid anesthesia may be difficult to treat, especially if the gallstones are unsuitable for oral dissolution or lithotripsy. We describe our experience with a minimally invasive surgical method of gallstone extraction under thoracic epidural or intercostal anesthesia. STUDY DESIGN: Eight-one patients who were either at high risk from or did not wish to undergo general anesthesia or those who wished to conserve their gallbladder underwent percutaneous cholecystolithotomy with a modified cholecystoscope. Of these patients, 63 (78 percent) were in American Society of Anesthesiology grades III and IV and 28 (35 percent) had thick-walled, diseased gallbladders. RESULTS: Gallstones were completely cleared in 66 (81 percent) patients and complete symptom relief was obtained in more than 95 percent of these patients. There were no deaths or serious complications. CONCLUSIONS: Percutaneous cholecystolithotomy under regional anesthesia is an effective means of gallstone treatment in selected high-risk patients.

Adult↗
PubMed1997

Effect of cisapride on oesophageal motility and duodenogastro-oesophageal reflux in patients with Barrett's oesophagus.

OBJECTIVE: Both gastric acid and duodenal juice have been implicated in Barrett's oesophagus. The aim of this study was to look at duodenal reflux in the oesophagus together with motility characteristics in a group of patients with Barrett's oesophagus and compare them with a mild oesophagitis group and to assess the effect of cisapride on any abnormalities. DESIGN: A prospective study comparing the two groups of patients was carried out. METHODS: Twenty patients with histologically proven Barrett's oesophagus and 20 patients with Savary-Miller grade 2 oesophagitis were studied. Standard oesophageal manometric measurements were carried out and on a separate occasion duodenogastro-oesophageal reflux (DGOR) was measured over a 4-h period using a sodium ion selective electrode. Patients with more than 5% DGOR were given cisapride (10 mg four times daily) and the studies repeated after 7 days of treatment. RESULTS: Barrett's patients showed more DGOR, 12.2% of the study time compared to 5.1% in the mild oesophagitis group, P = 0.012, but manometric findings were not significantly different. Sixteen patients were treated with cisapride. DGOR was reduced in 8 out of 12 Barrett's patients and 2 out of 4 oesophagitis patients, and proximal amplitude and distal oesophageal pressures were significantly elevated (P = 0.05 and P = 0.03, respectively). CONCLUSION: Monitoring of sodium ions in the oesophagus shows that patients with Barrett's oesophagus have significantly more DGOR than patients with uncomplicated oesophagitis and cisapride may be effective in removal of this reflux.

Adult↗
PubMed1996

Randomised, prospective, single-blind comparison of laparoscopic versus small-incision cholecystectomy.

BACKGROUND: We report a prospective randomised comparison between laparoscopic and small-incision cholecystectomy in 200 patients which was designed to eliminate bias for or against either technique. METHODS: Patients were randomised in the operating theatre and anaesthetic technique and pain-control methods were standardised. Four experienced surgeons did both types of procedure. Identical wound dressings were applied in both groups so that carers could be kept blind to the type of operation. FINDINGS: There was no significant difference between the groups for age, sex, body mass index, and American Society of Anaesthesiologists grade. Laparoscopic cholecystectomy took significantly longer than small-incision cholecystectomy (median 65 [range 27-140] min vs 40 [18-142] min, p<0.001). The operating time included operative cholangiography which was attempted in all patients. We found no significant difference between the groups for hospital stay (postoperative nights in hospital, median 3-0 [1-17] nights for laparoscopic vs 3-0 [1-14] nights for small-incision, p=0.74), time back to work for employed persons (median 5-0 weeks vs 4.0 weeks; p=0.39), and time to full activity (median 3-0 weeks vs 3.0 weeks; p=0.15). INTERPRETATION: Laparoscopic cholecystectomy takes longer to do than small-incision cholecystectomy and does not have any significant advantages in terms of hospital stay or postoperative recovery.

Analgesia, Patient-Controlled↗
PubMed1996

Histamine-2 receptor antagonists and gastric cancer.

We conducted a case-control study at Group Health Cooperative of Puget Sound to evaluate the relation between longterm histamine-2 (H2) receptor antagonist use and gastric cancer. We identified 113 cases and 452 controls and estimated a relative risk (RR) of 2.0 [95% confidence interval (C1) = 1.0-3.9]. When we evaluated the effect of time-since-first-use, the RR estimates were 6.5, 1.2, and 1.0 for 2-4 years of use, 5-9 years, and > or = 10 years, respectively. The data provide substantial evidence that long-term H2 antagonist use is not associated with gastric cancer.

Aged↗
PubMed1996

M235-->T polymorphism of the angiotensinogen gene predicts hypertension in the elderly.

OBJECTIVE: To determine whether the M235-->T polymorphism (exon 2) of the angiotensinogen gene is associated with hypertension in elderly patients with isolated systolic hypertension [ISH: systolic blood pressure (SBP) > or = 160 mmHg, diastolic blood pressure (DBP) < 90 mmHg) or systolic-diastolic hypertension (SDH: DBP > or = 90 mmHg, SBP > or = 160 mmHg) compared with normotensive controls (SBP < 160 mmHg, DBP < 90 mmHg). DESIGN: A case-control study in 769 non-institutionalized, elderly (aged > or = 60 years; female:male ratio 0.85) residents of Dubbo, New South Wales. METHODS: Individuals were classified as having ISH (n = 171), having SDH (n = 218) and being normotensive controls (n = 366) with age and sex matching. MM, TT and MT genotypes were determined by a nested polymerase chain reaction strategy using DNA extracted from serum. The prediction of ISH or SDH by genotype or allele was examined in a multiple-logistic regression model that controlled for various confounders. RESULTS: SBP (mean +/- SD, mmHg)/DBP (mean +/- SD, mmHg) was 176 +/- 16/79 +/- 8 in the ISH group, 167 +/- 23/97 +/- 7 in the SDH group and 134 +/- 14/74 +/- 9 in the normotensive control group. The frequencies of M and T alleles in the normal population (0.69 and 0.31, respectively) were altered significantly in the ISH group (0.61 and 0.39, respectively; chi 2 = 6.0, P < 0.02) and the SDH group (0.62 and 0.38, respectively; chi 2 = 6.0, P < 0.02). The presence of the TT genotype predicted both ISH (odds ratio 1.9, 95% confidence interval 1.1-3.3) and SDH (1.7, 1.0-3.0) as did that of the T allele (ISH: 1.3, 1.0-1.7; SDH: 1.3, 1.0-1.7). CONCLUSIONS: The M235-->T polymorphism may be a marker for both forms of hypertension in the elderly. Whether the TT genotype represents a genetic risk factor for the development of hypertension in later life requires confirmation.

Aged↗
PubMed1996

Uncoupled defense gene expression and antimicrobial alkaloid accumulation in elicited opium poppy cell cultures.

Treatment of opium poppy (Papaver somniferum L.) cell cultures with autoclaved mycelial homogenates of Botrytis sp. resulted in the accumulation of sanguinarine. Elicitor treatment also caused a rapid and transient induction in the activity of tyrosine/dopa decarboxylase (TYDC, EC 4.1.1.25), which catalyzes the conversion of L-tyrosine and L-dopa to tyramine and dopamine, respectively, the first steps in sanguinarine biosynthesis. TYDC genes were differentially expressed in response to elicitor treatment. TYDC1-like mRNA levels were induced rapidly but declined to near baseline levels within 5 h. In contrast, TYDC2-like transcript levels increased more slowly but were sustained for an extended period. Induction of TYDC mRNAs preceded that of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) mRNAs. An elicitor preparation from Pythium aphanidermatum was less effective in the induction of TYDC mRNA levels and alkaloid accumulation; however, both elicitors equally induced accumulation of PAL transcripts. In contrast, treatment with methyl jasmonate resulted in an induction of TYDC but not PAL mRNAs. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and the protein kinase inhibitor staurosporine partially blocked the fungal elicitor-induced accumulation of sanguinarine. However, only staurosporine and okadaic acid, an inhibitor of protein phosphatases 1 and 2A, blocked the induction of TYDC1-like transcript levels, but they did not block the induction of TYDC2-like or PAL transcript levels. These data suggest that activation mechanisms for PAL, TYDC, and some later sanguinarine biosynthetic enzymes are uncoupled.

Acetates↗
PubMed1996

Molecular characterization of berberine bridge enzyme genes from opium poppy.

In Papaver somniferum (opium poppy) and related species, (S)-reticuline serves as a branch-point intermediate in the biosynthesis of numerous isoquinoline alkaloids. The berberine bridge enzyme (BBE) ([S]-reticuline:oxygen oxidoreductase [methylene bridge forming], EC 1.5.3.9) catalyzes the stereospecific conversion of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon of (S)-scoulerine and represents the first committed step in the pathway leading to the antimicrobial alkaloid sanguinarine. Three unique genomic clones (bbe1, bbe2, and bbe3) similar to a BBE cDNA from Eschscholtzia californica (California poppy) were isolated from opium poppy. Two clones (bbe2 and bbe3) contained frame-shift mutations of which bbe2 was identified as a putative, nonexpressed pseudogene by RNA blot hybridization using a gene-specific probe and by the lack of transient expression of a chimeric gene fusion between the bbe2 5' flanking region and a beta-glucuronidase reporter gene. Similarly, bbe1 was shown to be expressed in opium poppy plants and cultured cells. Genomic DNA blot-hybridization data were consistent with a limited number of bbe homologs. RNA blot hybridization showed that bbe genes are expressed in roots and stems of mature plants and in seedlings within 3 d after germination. Rapid and transient BBE mRNA accumulation also occurred after treatment with a fungal elicitor or with methyl jasmonate. However, sanguinarine was found only in roots, seedlings, and fungal elicitor-treated cell cultures.

Amino Acid Sequence↗
PubMed1996

In vitro contractility of stimulated and non-stimulated human gallbladder muscle.

In an attempt to define, more clearly, the nature of gallbladder contraction we obtained muscle strips from human gallbladder wall, removed at cholecystectomy. Samples were taken from various areas of the gallbladder to seek evidence of a dominant axis of contraction. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8) and carbachol, and, to determine maximal contractile force, 0.25 M potassium chloride. No differences were seen between samples taken from the long-itudinal, circular and oblique axes. In a second series of experiments, samples were taken from the body and neck regions of the gallbladder. In these, it was seen that the samples from the body contracted more forcefully than those of the neck tissue and that they were more sensitive to carbachol stimulation. The difference in response to CCK-8 measured in the strips from the body and cystic duct/neck of the gallbladder cannot be explained by a difference in sensitivity to CCK-8, but is mainly due to the difference in the amount of muscle tissue present. Strips from the body are more sensitive to muscarinic stimulation that those from the neck. Overall, there is a functional difference in sensitivity between the body and neck which would serve to facilitate bile flow into the common bile duct during gallbladder contraction.

Carbachol↗
PubMed1996

Detection of duodenal fluid in the oesophagus with a sodium ion selective electrode.

The assessment of duodeno-oesophageal reflux is difficult as, until recently, no technique has been readily available for continuous ambulatory monitoring. A sodium ion selective electrode placed in the stomach has been previously shown to detect duodenogastric reflux by using sodium as a marker. This relies on the difference in sodium concentration between gastric (5-60 mmol/L) and duodenal, biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the efficacy of the electrode in the distal oesophagus, eight subjects without symptomatic gastro-oesophageal reflux and eight subjects with known duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of the electrode to sodium ions. In both groups, this revealed a constant and reproducible rise in response with increasing concentration (P < 0.0001). The stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric tube to obtain 12 different samples of gastric fluid. This was assayed for sodium and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent to 40-72 mmol/L Na+ was recorded by the electrode in response to samples that contained 58-81 mmol/L Na+ and 0.4-16 mmol/L bile acids, recorded by quantitative analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005-0.6 mmol/L. The response was appropriate to the assayed bile acid concentration in all but one sample. The sodium ion selective electrode responds to bile containing fluids introduced into the oesophagus. Further investigation is warranted to determine its ability to measure duodeno-oesophageal reflux continuously.

Bile Acids and Salts↗