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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
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↗
PubMed1979

Evaluation of an intraoperative test for the completeness of vagotomy.

An intraoperative test for the completeness of vagotomy has been evaluated in 103 consecutive operations, including proximal gastric, selective and truncal vagotomies, and truncal vagotomy with antrectomy. At the completion of the vagotomy a pH probe was used to test gastric mucosal response to an intravenous infusion of pentagastrin, aiming to detect undivided vagal fibres by localizing residual areas of acid secretion. Testing was performed in 86 out of 103 vagotomies, and in only 34% was the vagotomy judged complete at the first attempt. Residual areas of acid secretion (usually small) were detected in the remainder, and in early all of these it was possible to abolish these areas by dividing further vagal fibres. It is suggested that intraoperative pH testing improves the likelihood of a complete vagotomy. The test is also useful to plot precisely the antral-body junction when antrectomy is combined with vagotomy.

Gastric Acidity Determination↗
PubMed1978

Suppression of the immune response in C3H/HeJ mice by protein-free lipopolysaccharides.

The experiments described herein demonstrate the plaque-forming cell response of C3H/HeJ mice can be suppressed by a Boivin type lipopolysaccharide (LPS) and a deproteinized glycolipid. Suppression was observed both in vivo and in vitro, and could be transferred to normal cells in coculture experiments. This newly discovered effect of LPS in C3H/HeJ mice indicates that the adjuvant and inhibitory action of LPS may be distinct phenomena which are under different genetic regulation. Thus, the C3H/HeJ strain provides a convenient animal model for study of immunosuppression independent of the adjuvant effect.

Animals↗