Spontaneous staphylococcal peritonitis in an otherwise healthy young man.
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Adult↗
Biomedical subjects
A G Johnson
Publications and source records attributed to A G Johnson.
In vivo activation of macrophages by prolactin from young and aging mice.
Ovine prolactin (PRL), a pituitary hormone, which has been shown to modulate a variety of T-cell immune responses, was tested for its capacity to elevate the respiratory burst and phagocytosis of peritoneal macrophages from three strains of young and aging mice following i.p. injection. The results were as follows. (a) PRL was found to enhance superoxide anion (O2-) generation and hydrogen peroxide (H2O2) release from macrophages removed from 2-3 months old young male and young female mice of the C3H/HeN, BALB/c and Swiss Webster (SW) strains. (b) PRL also increased the respiratory burst of aging mice of C3H/HeN (14-15 months old) and BALB/c (20-22 months old), but not the aging (13-15 months old), outbred, SW strain. (c) PRL-induced total H2O2 release was greater in young than aging mice, C3H/HeN and BALB/c mice, although the fold increase was similar; however, O2- generation was similar between young and aging mice of these strains. In SW mice, both O2- generation and H2O2 release were higher in young than in aging mice. (d) A statistically significant gender related difference was observed only in the H2O2 assay where young male BALB/c mice responded more strongly than young females. (e) Finally, phagocytosis of Candida albicans by macrophages from C3H/HeN mice was enhanced by PRL, with no demonstrable differences among young male, young female and aging male mice.
Aging↗
Non-steroidal anti-inflammatory drugs and hypertension in the elderly: a community-based cross-sectional study.
1. Whether non-steroidal anti-inflammatory drug (NSAID) usage in the elderly elevates blood pressure or antagonises the blood pressure-lowering effect of antihypertensive medication is presently unknown. The primary aims of this study were to estimate the prevalence of NSAID usage, to evaluate the prescription of NSAIDs for arthritis and to determine whether NSAID usage was an independent predictor of hypertension in a large elderly community. 2. All non-institutionalised elderly (> 60 years) residents of Dubbo, NSW who attended for a baseline assessment were enrolled (1237 males, 1568 females). A questionnaire was administered and blood pressure was measured according to the Prineas protocol. The frequency of NSAID usage was determined, with stratification by age, sex, blood pressure group and history of arthritis. 3. NSAID usage was 26% overall (females 28%, males 23%), increased with age and was higher in females than males for every age group studied. Amongst patients with a past history of 'arthritis', 45% were using NSAIDs. Twelve percent were taking NSAIDs and antihypertensive medication concurrently, constituting the population at risk of an adverse drug-drug interaction. Employing a multiple logistic regression model which adjusted for several confounders in the cross-sectional analysis, NSAID usage significantly predicted the presence of hypertension (odds ratio: 1.4, 95% confidence interval: 1.1-1.7) with an attributable risk of 29%. 4. Amongst non-institutionalised elderly persons, NSAID usage may be an independent risk factor for hypertension. Considering the substantial consumption of NSAIDs by elderly patients, physicians should review their NSAID prescribing patterns for this community group.
Age Factors↗
Measurement of gastric emptying in infants with pyloric stenosis using applied potential tomography.
Gastric emptying in a group of 49 vomiting infants with infantile hypertrophic pyloric stenosis (IHPS) was investigated using applied potential tomography. Fourteen asymptomatic infants were also studied as a control group. A Dioralyte test feed (25 ml/kg/feed) was used for all the studies. The infants with IHPS were investigated before and at two, four, and seven days after an operation; the other infants were investigated once. The results show that the infants with IHPS have no or little gastric emptying before the operation and gradually return to normal emptying by the seventh day after the operation. A significant difference in gastric emptying was noted between the control infants and the infants with IHPS before and at two and four days after the operation. The applied potential tomography method is suitable for studying gastric emptying in infants, with no morbidity nor complications. It also allows multiple studies to be performed without upset or discomfort.
Electric Impedance↗
Acid, motility, and ulcers: a comparison of cisapride with placebo in the prevention of duodenal ulcer relapse.
In a single centre double blind study of 66 patients, the value of cisapride (10 mg twice daily) was compared with placebo in the prevention of duodenal ulcer relapse. Patients who remained ulcer free attended for clinical review every two months and had a mandatory endoscopy at 0, 4, 8, and 12 months or if symptoms suggestive of ulcer recurrence developed. The 12 month crude relapse rates (that underestimate the probability of ulcer recurrence) showed that cisapride was superior to placebo (34% (11/32) relapsed on cisapride v 68% (23/34) on placebo, p = 0.007). This finding was confirmed using lifetable analysis, with a 35% reduction (95% confidence intervals 10-59%, p < 0.05) in the proportion of ulcer relapses in patients who had received cisapride compared with those treated with placebo. These results are similar to those reported in maintenance trials of H2 receptor antagonists analysed by the same method. Drug related adverse clinical events were mainly trivial, but led to three patients on cisapride and one on placebo withdrawing from the trial.
Adolescent↗
Duodenogastric reflux after gastric surgery and in gastric ulcer disease: continuous measurement with a sodium ion selective electrode.
Duodenogastric reflux (DGR) was investigated with a sodium ion selective electrode in 10 normal controls, 10 patients with persistent pain after gastric surgery, and five patients with gastric ulcer. During an average study time of two and a half hours, normal controls had reflux for 12% of the study, whereas patients after gastric surgery had reflux for 91% of the study time (p < 0.0002). Patients with a gastric ulcer had reflux on average for 67% of the study (p < 0.001). The patients who had had gastric surgery had several symptoms, but there was no association between the number or nature of symptoms and the severity of DGR as determined by the sodium electrode. Patients with positive bile provocation tests did not show any significant difference in the duration of reflux compared with those with a negative provocation test (79% and 87%). There was also no relation between the results of the provocation test and the number and nature of symptoms. Continuous monitoring of intragastric sodium ions with a selective electrode is a practical means of assessing DGR. Results suggest that symptoms due to DGR may be related to the sensitivity of the gastric lining as well as the amounts of duodenal contents flowing back into the stomach.
Adult↗
Extracorporeal shock wave lithotripsy and gall bladder stones.
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Cholelithiasis↗
Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). Recognition, management and avoidance.
The prevalence and incidence of adverse drug interactions involving nonsteroidal anti-inflammatory drugs (NSAIDs) remains 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 those 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, and prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to the risk of haemorrhage, and for patients taking high-dose methotrexate due to the dangers of bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified as toxicity may be increased without any improvement in efficacy. Where lithium or anti-hypertensives are coprescribed with NSAIDs, close monitoring is mandatory for lithium toxicity and hypertension, respectively, and aspirin (acetylsalicylic acid) or sulindac are preferred. Phenytoin or oral hypoglycaemic agents may be administered with NSAIDs other than pyrazoles and salicylates provided that 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 triamterene should be avoided due to the risk of renal failure. High dose aspirin should be replaced by naproxen in patients on valproic acid (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. Adverse drug interactions involving NSAIDs may be limited by rational prescribing and by careful monitoring, particularly for high-risk patients, drugs and therapy periods.
Animals↗
Change in arginine vasopressin concentrations with age.
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Adult↗
Randomised controlled trial of cost-effectiveness of lithotripsy and open cholecystectomy as treatments for gallbladder stones.
Inpatient extracorporeal shockwave lithotripsy for treatment of gallbladder stones has not previously been compared with open cholecystectomy in terms of cost-effectiveness. In a randomised controlled trial, 163 patients, stratified by gallstone bulk (over 4 cm3 or not), were randomised to lithotripsy or cholecystectomy (38 large-bulk and 27 small-bulk cholecystectomy; 37 large-bulk and 61 small-bulk lithotripsy) and followed up for 1 year. Both treatments gave significant health gains in terms of a reduction in episodes of biliary pain, improved perceived health status, and symptom relief, but few differences between treatments were found. There was some evidence that biliary-pain episodes were less severe after cholecystectomy. Cholecystectomy patients also had greater improvements in mean health gain for three related symptoms: vomiting, feeling sick, and fatty-food upset. However, there were no differences between groups in perceived health status. Among lithotripsy patients, health gain was not related to stone clearance. Lithotripsy was more expensive than cholecystectomy, principally because of the costs of the inpatient stay and adjuvant bile-salt therapy. Conventional lithotripsy appears at least as cost-effective as cholecystectomy for patients with small-bulk stones but less cost-effective for those with large-bulk stones. To some extent treatment choice can be guided by patient preference.
Adult↗
Suppression of antibody forming cells by lipid A analogs.
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Animals↗
Immunosuppression induced by non-reducing acylated monosaccharide subunits of lipid A.
Synthetic acylated glucosamine monosaccharides, representative of the non-reducing subunit of lipid A, were compared for their ability to induce non-specific suppression of antibody forming cells. Five of nine analogs were found to be functional in this respect, indicating that these compounds, carrying a phosphate at C4 and acyl substituents at C2 and C3 are the smallest synthetic analogs of lipid A capable of eliciting non-specific immunosuppression. A comparison of the analogs inducing suppression with those testing negative revealed that (i) a single 3-hydroxymyristoyl group at C2 is common to 4/5 analogs inducing suppression; (ii) addition of an oxytetradecanoyl group to the 3-hyroxymyristoyl group at either C2 or C3 negated suppression; and (iii) extreme specificity was exhibited in suppression induction such that substitution of either lauric (C12) or palmitic (C16) for myristic acid (C14) at C2 voided transmission of the suppressive signal.
Animals↗
Polyadenylic: polyuridylic acid-induced determinants of host resistance to cytomegalovirus and their potentiation by hyperthermia.
The ability of spleen cells from poly A:poly U-treated mice to inhibit murine cytomegalovirus (MCMV) replication in confluent monolayer cells of secondary mouse embryo fibroblasts (MEFs) cultured at 37 and 40 degrees C was investigated. When spleen cells from BALB/c mice injected 48 h earlier with poly A:poly U were added to MEFs infected 2 h previously with MCMV, 37% less plaques were observed than in cultures containing control cells. Of interest, the poly A:poly U-induced antiviral activity at the elevated temperature (40 degrees C) resulted in a further drop to 61% in MCMV-induced plaques compared to those of the normothermic (37 degrees C) cultures. The antiviral function of spleen cells induced by poly A:poly U was evident in the supernatant fluid when cultured for 48 h at 37 degrees C. MCMV-induced plaques were reduced to 52 and 5% of controls in the plaque assays performed at 37 and 40 degrees C, respectively. Supernatant fluids generated at 40 degrees C, however, inhibited MCMV replication only when incubated at 40 degrees C. No direct inhibitory effect of the supernatant fluids on MCMV was evident; rather, inhibition was effected directly on the MEFs. The NK cell fraction of spleen cells from poly A:poly U-treated mice alone showed only a slight inhibitory effect at 40 degrees C. However, in the presence of the supernatant fluid from poly A:poly U-exposed spleen cells, the antiviral activity of NK cells was significantly increased both at 37 and 40 degrees C. The cellular source of the culture fluid showing poly A:poly U-induced antiviral activity appeared to be in the T-cell population. It was completely neutralized by monoclonal anti-IFN gamma antibody but not by anti-IFN beta, anti-IL4, anti-transforming growth factor, or anti-prostaglandin E2. In conclusion, these data document the ability of spleen cells from poly A:poly U-treated mice to inhibit MCMV replication and this activity is potentiated by hyperthermic conditions. The antiviral function of poly A:poly U-treated spleen cells appeared to be due mainly to the action of IFN gamma produced by T cells. The enhanced antiviral activity by hyperthermia appeared to be related to the action of IFN gamma rather than its production.
Animals↗
Improved high-performance liquid chromatographic method for the determination of indomethacin in plasma.
Indomethacin is an inhibitor of prostaglandin synthesis and has several uses, including the ability to encourage closure of a patent ductus in premature neonates. A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring plasma concentrations of indomethacin. An acidic buffer (citrate, pH 3.0) was employed to alter the pH of the aqueous phase prior to extraction to minimise interference interference from endogenous compounds. Extraction of indomethacin from plasma was optimally achieved with petroleum ether (boiling fraction of 40-60 degrees C):dichloromethane (50:50). However, separation of indomethacin from plasma proteins was attempted unsuccessfully using acetonitrile precipitation; severe band broadening occurred due to injected sample solvent problems. The absolute recoveries for indomethacin and internal standard (mefenamic acid) were over 90% (n = 3). Precision was expressed as the coefficient of variation (n = 4), which was less than or equal to 8% at each of six indomethacin concentrations in the range 50-2,000 ng/ml. The limit of quantitation of indomethacin in plasma was 50 ng/ml (0.5 ml of plasma injected). We report an HPLC method for the quantitation of indomethacin in plasma that may have widespread applicability for routine drug assay laboratories.
Chromatography, High Pressure Liquid↗
Polyadenylic:polyuridylic acid-induced protection of BALB/c mice against acute murine cytomegalovirus infection.
Treatment of BALB/c mice with poly(A):poly(U) 18 h prior to infection with a lethal dose of murine cytomegalovirus (MCMV) increased survival. In parallel with increased survival, a 10- to 100-fold reduction of plaque-forming MCMV was found in the liver and spleen of mice 4 days post-infection with a sublethal dose of MCMV. Poly(A):poly(U) did not significantly increase natural killer cell activity or prolong the duration of elevated cytotoxic activity in infected animals. The possible role of interferon in the poly(A):poly(U)-induced protection of BALB/c mice is discussed.
Animals↗
A prospective trial of endoscopic sclerotherapy v oesophageal transection and gastric devascularisation in the long term management of bleeding oesophageal varices.
In a prospective three centre study oesophageal transection and gastric devascularisation have been compared with endoscopic sclerotherapy in the long term management of bleeding oesophageal varices. Cirrhotic patients (Child's A or B grade) with documented bleeding oesophageal varices were treated initially with emergency sclerotherapy, and after five days stability, were allocated to one of the two treatment regimes. The endoscopic sclerotherapy group underwent regular sclerotherapy until variceal obliteration while those undergoing surgery were not endoscoped unless bleeding recurred, when they were treated by sclerotherapy if appropriate. Ninety two patients were eligible for analysis (68% alcoholic cirrhosis; mean age 50.1 years) and follow up was achieved for a mean of 52.5 months (range 17-83). Mortality in the first three months was greater in the oesophageal transection and gastric devascularisation group (20% v 1%) but by two years the survival curves were the same and thereafter there was no difference in mortality. Rebleeding occurred in 13/41 (31%) patients, undergoing oesophageal transection and gastric devascularisation. The costs incurred during the first year of oesophageal transection and gastric devascularisation treatment were significantly greater than with endoscopic sclerotherapy (4369 pounds v 1067 pounds, p < 0.0001) and the high rate of rebleeding in the surgical group meant that no cost savings occurred in subsequent years. It is concluded that oesophageal transection and gastric devascularisation confers no benefit over endoscopic sclerotherapy in terms of long term survival and that it is not cost effective as judged by the current health care costs in the United Kingdom.
Adult↗
Continuous monitoring of sodium ion concentration in the human stomach--a new technique for the detection of duodenogastric reflux.
Measurement of sodium ion concentration in gastric juice offers a simple means of detecting duodenogastric reflux (DGR). Using aspirated gastric juice, we measured sodium ion concentration, bile acid levels and phospholipase A2 activity and found that sodium ion levels increase along with these other standard markers during DGR. Following this, using a sodium ion selective electrode and a portable data logger, continuous recordings of sodium ion concentration were made in the human stomach. These studies demonstrated the ability of sodium ion monitoring to detect major DGR episodes in the body of the stomach.
Adult↗
Protodyne: an immunostimulatory protein component, prepared from gram-positive Bacillus subtilis.
A protein component derived from bacterial protoplasm, called Protodyne, increases the non-specific resistance to infections by bacteria and viruses. Here we show that Protodyne can be prepared not only from Gram-negative bacteria, but also from Gram-positive bacilli. Several preparations of Protodyne, prepared from Bacillus subtilis by phenol extraction or by ammonium sulfate precipitation, were evaluated for immunomodulatory activities in a variety of assays. Protodyne had a marked mitogenic activity on mouse spleen cells; it was a potent inducer of tumor necrosis factor (TNF) and stimulated production of interleukin-1 (IL-1) in human peripheral blood mononuclear cells; it increased the capacity of activated macrophages to undergo a respiratory burst, to produce intracellular killing of leishmanial parasite and extracellular lysis of mastocytoma cells; it also stimulated phagocytosis of latex particles, and prolonged survival of immunosuppressed mice infected with Pseudomonas aeruginosa. These activities were not inhibited by polymyxin B, indicating that the activity of Protodyne is not the result of contamination with exogenous lipopolysaccharide. It appears that Protodyne exerts its many immunomodulatory actions by inducing the release of soluble mediators, including TNF and IL-1.
Adjuvants, Immunologic↗