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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 109 records · Page 6Linked to original sources

Teaching evolution.

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Biological Evolution↗

Long-term results of highly selective vagotomy: a prospective study with implications for future laparoscopic surgery.

Between 1979 and 1984, 141 patients (110 men, 31 women) underwent highly selective vagotomy (HSV) by a standard open technique for duodenal ulcer. All patients had received preoperative treatment with full-dose H2-receptor antagonists. Some 107 of these patients underwent HSV for persistent relapse on withdrawal of H2-receptor antagonists (relapsing responders) and 30 because of non-response to such drugs. After 4 years of follow-up, non-responders were found to be more likely to have symptoms after operation (P < 0.001), but did not have a higher rate of recurrent ulceration. At a median of 11 (range 8-14) years after operation 126 patients were still alive; 115 (91 per cent) of these were followed up. Ten patients (9 per cent) were found to have had endoscopically proven recurrence and eight (7 per cent) still had symptoms without evidence of recurrence. The endoscopic recurrence rate and symptom rate at 11 years were no longer significantly different between relapsing responders and non-responders. The preoperative response to H2-receptor antagonist therapy does not help in predicting the likelihood of ulcer recurrence or long-term symptoms after HSV. Post-operative symptoms do not necessarily predict long-term ulcer recurrence. The long-term endoscopic recurrence rate after HSV is low and, if equally good results can be obtained laparoscopically, this will be an important and cost-effective option in the management of duodenal ulcer.

Adolescent↗

Arginine vasopressin and osmolality in the elderly.

OBJECTIVES: To evaluate the influence of age on plasma arginine vasopressin (AVP) concentrations and the relationship between plasma AVP and serum osmolality in younger and older subjects, and in the elderly, to assess the effect of gender on plasma AVP concentration and to determine the impact of prostaglandin blockade on renal responsiveness to AVP. DESIGN: Cross-sectional study; randomized, double-blind, crossover, placebo-controlled study. SETTING: The Renal Laboratory, Royal North Shore Hospital (younger adults) and Clinical Room, St Vincents Hospital (elderly subjects). PARTICIPANTS: 45 younger adults (35 +/- 9 years), and 41 elderly subjects (29 males, 12 females; 78 +/- 3 years). All subjects were healthy and non-institutionalized. The elderly subjects were screened to exclude significant pathology (clinical assessment, multiple investigations). INTERVENTION: Blood samples were drawn from all younger and elderly subjects. The elderly subjects were randomly allocated indomethacin or placebo for 1 month. Following a 1 to 2-week washout, the alternative was administered for a further 1 month. MAIN OUTCOME MEASURES: Plasma AVP and serum osmolality and plasma AVP, serum, and urine osmolality at baseline were measured on indomethacin and placebo. RESULTS: In the elderly subjects, baseline plasma AVP concentration was significantly higher than in the younger subjects studied (4.7 +/- 0.7 vs 2.1 +/- 0.2 pg/mL respectively; P = 0.0003). Plasma AVP was strongly correlated with serum osmolality in the younger subjects (r = 0.76, P = 0.0001) but not in the elderly cohort (r = -0.18, P = 0.26). No difference was found between the sexes in plasma AVP (P = 0.89), and indomethacin treatment did not alter the plasma AVP/urine osmolality ratio (P = 0.85) in the elderly subjects. In addition, changes in plasma AVP with indomethacin therapy did not correlate with changes in serum osmolality (r = 0.16, P = 0.09). CONCLUSIONS: Aging is accompanied by an increase in plasma AVP concentrations. In healthy, elderly subjects, plasma AVP is not dependent on serum osmolality and is not influenced by gender. Indomethacin has no effect on the renal responsiveness to plasma AVP.

Adult↗

Molecular adjuvants and immunomodulators: new approaches to immunization.

Epitopes on microbial antigens responsible for protective immunity have begun to be identified and isolated, and their chemical structures have been determined. Ensuing knowledge of their weak immunizing capacity per se has led to an appreciation of the need for adjuvants to increase the immunogenicity of these low-molecular-weight synthetic structures. As such, a recent surge in adjuvant research has emerged. Accordingly, this review will highlight a number of those adjuvant substances whose activity in animals indicates a potential use in human vaccines. In addition, the potential of several well-defined substances, termed immunomodulators, which nonspecifically stimulate resistance of animals to multiple 50% lethal doses of microbial challenge is described. Among the most extensively characterized adjuvants of microbial origin discussed in detail are (i) the lipopolysaccharides isolated from gram-negative bacteria and their nontoxic analogs, (ii) the synthetic muramyl dipeptides and their multiple analogs, and (iii) the synthetic polyribonucleotide complexes, mimicking the interferon-inducing capacity of viruses. Discussed also are the heat-labile enterotoxin of Escherichia coli, the nonionic block copolymers, the saponins, a quinolamine derivative, and the hormone dihydroepiandrosterone.

Acetylmuramyl-Alanyl-Isoglutamine↗

Cost effectiveness of adjuvant bile salt treatment in extracorporeal shock wave lithotripsy for the treatment of gall bladder stones.

The relative cost effectiveness of adjuvant urso and chenodeoxycholic acid treatment in extracorporeal shockwave lithotripsy (ESWL) has been assessed as part of a pragmatic randomised controlled trial of ESWL as a treatment of gall bladder stones. Of the first patients with gall stone volume < 4 cm3 randomised to ESWL in the main trial, 24 were randomised to have ESWL alone and 26 to have adjuvant bile acid treatment, one of whom died before the end of the 12 month follow up period. At 12 months after treatment, differences in gall stone clearance between ESWL alone (3/24 (13%) clear, 5 (21%) referred for surgery) and ESWL and bile acids (6/25 (24%) clear, 2 (8%) referred for surgery) were not significant (p = 0.36, log rank test). Patients in both groups had substantial and significant health gains (according to biliary pain frequency and severity, Nottingham Health Profile scores, visual analogue scale symptom scores, and complications) but there were no significant differences between the groups. Improvements in both groups usually occurred within a few weeks of treatment and were unrelated to gall stone clearance. Costs were greater in the bile salt group (95% confidence intervals for estimated cost difference: 90 pounds to 630 pounds). If the purpose of treatment is symptom relief rather than gall stone clearance then adjuvant bile salt treatment seems to be unnecessary.

Adult↗

NSAID-related adverse drug interactions with clinical relevance. An update.

The prevalence and incidence of adverse drug interactions involving NSAIDs remain unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and interactions affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context. However, prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Adverse drug interactions involving NSAIDs may be restricted by rational prescribing and by careful monitoring, particularly high-risk patients, drugs and therapy periods. Prescribing NSAIDs is relatively contra-indicative for patients on oral anticoagulants due to hemorrhage and for patients taking high dose methotrexate due to bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified since toxicity may be increased without any improvement in efficacy. Where lithium or antihypertensives are coprescribed with NSAIDs, aspirin or sulindac are preferred and close monitoring is mandatory for lithium toxicity and hypertension respectively. Phenytoin or oral hypoglycemic agents may be administered with NSAIDs other than pyrazoles and salicylates, provided, the patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterine should be avoided due to the risk of renal failure, high dose aspirin should be replaced by naproxen in patients on sodium valproate and care is required when corticosteroids are administered to patients taking salicylates long term in high dosage. Interactions between NSAIDs and antacids or cholestyramine are generally avoidable by administering these drugs at different times.

Anti-Inflammatory Agents, Non-Steroidal↗

Laparoscopic fundoplication for gastro-oesophageal reflux.

The initial teaching and learning experience of four surgeons performing a laparoscopic Nissen fundoplication is reported. A total of 33 patients underwent the laparoscopic approach for Nissen fundoplication. Two patients also underwent concomitant cholecystectomy. A loose 360 degrees fundoplication secured by three or four sutures was performed, with 29 patients also undergoing posterior crural repair. Three operations were converted to open procedures. Two patients required subsequent surgery, one when the fundoplication and proximal stomach slipped into the chest and one for oesophageal obstruction. No other complications occurred. All patients are well and free of reflux symptoms at follow-up ranging up to 10 months (median 5 months). Operating time ranged from 47 min to 154 min (median 81 min) for fundoplication alone. The laparoscopic fundoplications with cholecystectomy required 145 and 170 min. Postoperative stay ranged from 3 to 12 days (median 3 days). Laparoscopic Nissen fundoplication is feasible in the management of gastro-oesophageal reflux disease. These early results demonstrate that this new technique may reduce some of the morbidity associated with open antireflux surgery. A prospective randomised study has been started to assess efficacy and benefits more thoroughly.

Adult↗

Evaluation of the accuracy and reproducibility of ambulatory blood pressure monitoring in the very elderly using the Takeda TM-2420.

The accuracy and reproducibility of ambulatory blood pressure monitoring (ABPM) were evaluated in the healthy elderly (> or = 75 years) using the Takeda TM-2420 ambulatory BP monitor (A & D Mercury, Australia). Accuracy was assessed from 90 standardised sphygmomanometer and simultaneously recorded TM-2420 BP measurements in 28 subjects with a BP range of 60-210 mmHg. Reproducibility was determined in 19 subjects who underwent four separate days of ABPM by calculating the standard deviation of the mean differences between pairs of recording days (sdd) and the coefficient of reliability (R). Adaptation was also assessed using R. Of 3471 BP measurements in 19 subjects over 76 recording days, 76% were valid readings. The TM-2420 overestimated simultaneously recorded sphygmomanometer measurements with a bias (mean difference, d +/- sdd) of 13.9 +/- 13.9 mmHg for SBP and 7.5 +/- 6.4 mmHg for DBP. The mean sdd between pairs of recording days was greater for SBP (20.0) than for DBP (9.4) but R was very high for both SBP (0.914) and DBP (0.904). Adaptation effects were not detected. ABPM with the TM-2420 is highly reproducible in the elderly. The TM-2420 performs acceptably in 'field' testing and as it overestimates cuff measurements consistently, appropriate adjustment of recorded TM-2420 BP should be possible in elderly individuals.

Aged↗

Future directions for conservative treatment of gallbladder calculi.

Recent conservative gallstone treatments provide rapid relief from symptoms, but all have a potential for stone recurrence. They are indicated in patients who are unfit or unwilling to undergo cholecystectomy. Wider application will depend on selection of patients who are at least risk of recurrence, or on development of effective prophylactic strategies.

Cholelithiasis↗