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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1992

Primary carcinoma of the gallbladder: a 10-year experience.

New developments in the management of gallstone disease, and particularly percutaneous and extracorporeal treatments that leave the mucosa intact, have renewed interest in the relationship between cholelithiasis and carcinoma. These treatments are both available in our hospital and to examine this question we studied the patients presenting between 1980 and 1990 with gallbladder cancer. The study comprised 21 patients with histologically proven carcinoma. The M:F ratio was 1:4 with a mean age of 76 years. Gallstones were present in 18 patients (85.7%). Ten patients remain alive today and in the 11 who died the median survival was 4 months. A preoperative diagnosis was made by ultrasound in only two patients. The lack of a preoperative diagnosis in the majority of patients is clearly a cause for concern and while our figures, like other series, do not establish a causal relationship with gallbladder carcinoma, it is vital to be diligent in the follow-up of high-risk patients (stones greater than 3 cm) with intact gallbladder mucosa after the treatment of stone disease.

Aged↗
PubMed1992

Simulated laparoscopic cholecystectomy.

A new simulator specifically designed for practising techniques in laparoscopic cholecystectomy is described. The simulator is inexpensive and utilises pig gallbladders. It allows a surgeon to practice without the need for assistance.

Animals↗
PubMed1991

Activation of macrophages from aging mice by detoxified lipid A.

A detoxified derivative of endotoxic lipopolysaccharides (LPS), monophosphoryl lipid A (MPL), which is capable of inducing nonspecific resistance against several infectious organisms, was tested for its capacity to activate peritoneal macrophages (M phi) from young and immunodeficient aging BALB/c and C3H/HeN mice. Superoxide generation and hydrogen peroxide release by M phi from aging mice were elevated following intraperitoneal injection with 25 micrograms of LPS or MPL, although they did not reach the peak levels achieved in LPS or MPL-treated young mice. Nitroblue tetrazolium reduction (NBT) by peritoneal M phi from aging C3H/HeN mice treated with MPL was higher than that in control aging mice, equalling that from MPL-treated young mice. LPS, its toxic counterpart, however, failed to increase NBT reduction in either group. MPL enhanced lysozyme activity in M phi from both aging and young C3H/HeN mice above initial control levels. On the other hand, LPS suppressed lysozyme activity in M phi from young, but not aging mice. Phagocytosis of Candida albicans by M phi from BALB/c mice was increased in both groups when stimulated by MPL, but not LPS. Similarly, MPL enhanced the ability to kill Candida in both aging and young BALB/c mice. This effect was not seen with LPS. Thus, a detoxified derivative of LPS was found capable of activating the respiratory burst, NBT reduction, elevating lysozyme activity, as well as phagocytosis and killing of Candida in murine peritoneal M phi from both young and aging mice.

Aging↗
PubMed1991

Applied potential tomography. Noninvasive method for measuring gastric emptying of a solid test meal.

Applied potential tomography (APT) is a new noninvasive, nonradioactive method of measuring gastric emptying, which generates profiles of emptying of liquids that are similar to those obtained simultaneously by scintigraphy and dye dilution. This study validates the ability of APT to measure emptying of a solid beefburger test meal from the stomach by comparing the results obtained with those obtained simultaneously by scintigraphy. When acid secretion was inhibited, there was a significant correlation between the two methods for the time taken for half the meal to empty from the stomach and the amount of meal emptied at different time intervals. Furthermore, the profiles of gastric emptying obtained by APT resembled those obtained by scintigraphy in most studies. If acid secretion was not inhibited, there was no correlation between values obtained by the two methods.

Adult↗
PubMed1991

Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration.

Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH.

Adult↗
PubMed1991

Characterization of immune suppression induced by polyribonucleotides.

Synthetic polyribonucleotide complexes, which have been shown to be potent adjuvants to the immune response of animals and humans were tested for their capacity to activate cells involved in suppressing antibody synthesis. Poly A:poly U and poly I:poly C inhibited murine antibody forming spleen cells when given 1-6 days before antigenic stimulus. To determine the cellular and molecular mediators of this suppression, individual cell populations were isolated or deleted and the resulting cell populations tested for induction of suppression. When the natural killer (NK) cell population was rendered non-functional with anti-asialo GM1 antiserum no diminution in suppressive activity was observed. Further experiments implicated adherent cells as the population responsible for mediating suppression. Supernatants from poly A:poly U-treated adherent cells were found both to contain increased levels of prostaglandin E (PGE) and to induce a significant decrease in antibody production when added to in vitro spleen cell cultures. In addition, indomethacin, an inhibitor of the cyclo-oxygenase pathway of the arachidonic acid cascade was found to reverse the suppression of antibody induced by poly A:poly U. Thus, the polyribonucleotide complexes appear to suppress antibody synthesis by inducing macrophages to secrete PGE, a known immune suppressant.

Animals↗
PubMed1991

A comparison of the immunomodulating properties of two forms of monophosphoryl lipid A analogues.

This investigation compared the immunomodulating activities of two forms monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD50 assays when compared to native lipopolysaccharides (LPS). The LD50 for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.

Adjuvants, Immunologic↗
PubMed1991

Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.

The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.

Adolescent↗
PubMed1991

Extracorporeal shock wave lithotripsy of gall stones: an in vitro comparison between an electrohydraulic and a piezoceramic device.

A comparative study of the effectiveness of two types of lithotripter in fragmenting gall bladder stones is reported. The machines used were a Piezolith 2300, which generates shock waves by the piezoceramic principle, and a Dornier MPL 9000, which produces the shock waves by underwater spark discharge. With each machine, corresponding stones of 45 pairs of weight and volume matched calculi (median volume 0.5 cm3, median diameter 10.5 mm) obtained at cholecystectomy were treated. All stones were successfully disintegrated (fragments smaller than 2 mm) with up to 5400 (median 628) shocks with the Piezolith and 3450 (median 428) shocks with the MPL 9000 lithotripters. With the Piezolith, operating at the highest power setting, a 1.65 fold median higher number of shocks was required for stone fragmentation than with the MPL 9000 at a medium power setting. Stone volume seemed to be the only determinant which affected ease of fragmentation; composition and density of the stones as assessed by computed tomography did not seem to be governing factors.

Cholelithiasis↗
PubMed1991

Primary carcinoma of the gallbladder.

Carcinoma of the gallbladder is a relatively rare malignancy which is difficult to diagnose. The advent of improved imaging methods and the expansion of interventional radiology however, combined with advances in surgical technique, has produced a change in attitude towards this tumour. The available world literature since 1960 has been reviewed and is presented in this article. However, whilst the outlook for diagnosis and treatment is improving, clearly the association with cholelithiasis (between 45% and 100%), is a cause for concern particularly with the advent of treatments (lithotripsy, percutaneous gallstone extraction) which leave gall bladder mucosa and residual fragments of stone in situ.

Aged↗
PubMed1991

The problems and pitfalls of NSAID therapy in the elderly (Part I).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide when grouped by generic categories and account for 3 to 9% of total prescription numbers in various countries. While NSAIDs are responsible for approximately 25% of all reported adverse drug reactions, aging may substantially increase the risk of NSAID-induced reactions. Several factors may contribute to NSAID-related toxicity in the elderly. The increase in morbidity associated with aging may result in consumption of a wide range of potent drugs, while inappropriate drug therapy and aberrant compliance are also capable of contributing to adverse drug reactions in geriatric patients. Age-related alterations in pharmacokinetics may influence the handling of NSAIDs in the elderly; in particular, dosage reduction is appropriate for azapropazone (apazone), naproxen, ketoprofen and salicylates administered to healthy aged patients, whereas the presence of renal disease may also necessitate dosage reduction of diflunisal, indomethacin, sulindac and mefenamic acid. Changes in NSAID pharmacodynamics with aging, such as increased CNS sensitivity to NSAIDs and impaired homeostasis, also predispose the elderly to NSAID-related adverse effects. It is undisputed that gastrointestinal toxicity due to NSAID therapy is a class effect. A significant association has been found between aspirin and uncomplicated gastric, but not uncomplicated duodenal ulcer, while nonaspirin NSAIDs are significantly associated with both uncomplicated gastric and duodenal ulceration. The use of NSAIDs is accompanied by a 2- to 5-fold risk of serious complications of peptic ulcer disease, i.e. haemorrhage or perforation, which increases in the elderly, particularly women. A broad range of renal side effects has been ascribed to NSAIDs, of which acute renal impairment is the most common in the elderly. Although most NSAIDs have been reported to cause hepatotoxicity, serious abnormalities of liver function are rare and are largely unpredictable. Other adverse effects due to NSAIDs have also been described, some of which (e.g. cardiovascular, CNS and haematological effects) may be more common in the elderly.

Aged↗
PubMed1991

The problems and pitfalls of NSAID therapy in the elderly (Part II).

The elderly are most susceptible to pharmacokinetic drug interactions between various NSAIDs and anticoagulants, sulphonylurea hypoglycaemic agents, certain anticonvulsants, methotrexate, digoxin, aminoglycosides and lithium. Pharmacodynamic interactions between some NSAIDs and antihypertensive drugs, anticoagulants, sulphonylurea agents and other NSAIDs are also potentially significant in the elderly. Despite the finding that mean therapeutic responses of large groups of patients have been generally equivalent for the wide range of NSAIDs studied thus far, it is also apparent that marked variability exists in the response of individual patients to different NSAIDs. Subsequent dosage increments may predispose 'nonresponders' and some less sensitive 'responders' to toxicity from NSAIDs. This interindividual variability in response to NSAIDs may be contributed to by the differing physicochemical properties of NSAIDs, physician prescribing habits and patient expectations, variations in NSAID pharmacokinetics, and the differing effects of NSAIDs other than their common ability to inhibit prostaglandin synthesis. The principles for drug prescribing in the elderly are no different from those that should be applied to the prescribing of medication in any patient. The clinician should strive to make a diagnosis and should avoid treating symptoms in isolation. Critical assessment of the indication for prescribing NSAID therapy must include consideration of the available effective and safe alternatives. If an NSAID is commenced the lowest effective dose should be the desired goal, but after an appropriate trial it is acceptable clinical practice to employ an alternative NSAID. There is no justification for combination NSAID therapy. The progress of each patient must be carefully monitored, particularly during the first few months of treatment, while periodic review of the ongoing need for the NSAID is essential.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Prophylactic sclerotherapy for esophageal varices: long-term results of a single-center trial.

Survival after prophylactic sclerotherapy was assessed in a single-center study involving 99 cirrhotic (41 alcoholic) patients enrolled over 8-yr. The wedged hepatic vein pressure gradient was measured; those with pressure greater than or equal to 12 mm Hg were randomized to receive sclerotherapy or no treatment. The rest were not randomized. Patients in all three groups who bled were treated with emergency endoscopy and sclerotherapy. Stratification according to presence of ascites was also undertaken. Median follow-up was 61 mo (range = 14 to 107 mo). Survival among unrandomized patients was significantly longer than among randomized patients (p less than 0.006), but there was no significant difference between those treated by sclerotherapy and the controls (p = 0.27). Alcoholic cirrhotic patients undergoing sclerotherapy had better 2-yr survival than did the controls (80% vs. 43%; p = 0.09), but this benefit was not sustained at 5 yr. Survival in the nonalcoholic patient groups was identical. Only 10 of 50 deaths were caused by variceal bleeding. Forty-eight percent of patients with large varices bled, compared with 20% of patients with small varices. Wedged hepatic vein pressure less than 12 mm Hg accurately identified alcoholic patients at low risk of variceal bleeding but not nonalcoholic patients. Only four episodes of variceal bleeding were attributable to elective sclerotherapy. We conclude that in our population, prophylactic sclerotherapy alone does not improve survival. The discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients suggests that factors other than variceal hemorrhage may be responsible for the difference.

Adolescent↗
PubMed1990

A functional psychosis precipitated by quinidine.

A 62-year-old man with a syndrome of gradually progressive cognitive deterioration accompanied by paranoid features is described. He had been taking quinidine since 1974 for a recurring supraventricular tachyarrhythmia. Examination revealed a suspicious man with widespread patchy cognitive deficits but no focal neurological signs. An exhaustive range of investigations gave unremarkable results. Within 24 hours of cessation of quinidine there was a dramatic improvement in his mental state and, after a further four days, he had returned essentially to normal with no demonstrable cognitive deficits. Several months later he suffered a recrudescence with prominent paranoid and depressive features which gradually settled after commencement of pimozide and dothiepin. It is likely that these events reflect a recurring functional psychosis which was precipitated or exacerbated in the first instance by quinidine. This represents a significant complication of quinidine therapy which has been largely unrecognized. Therapy with quinidine should be considered as a potential contributing factor in any patient with dementia or a functional psychosis who is also taking this drug.

Cognition Disorders↗