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Biomedical subjects

C G Gemmell

Publications and source records attributed to C G Gemmell.

At least 19 recordsLinked to original sources

Diagnostic tests for Helicobacter pylori: comparison and influence of non-steroidal anti-inflammatory drugs.

AIMS: To evaluate the efficacy of culture, histology, CLO-test, Helico-G and Pyloriset tests in diagnosing Helicobacter pylori in the presence or absence of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Of 134 patients studied, 75 had taken NSAIDs. At endoscopy, biopsy specimens were taken for culture, histology, and CLO-test. Blood was also taken for enzyme linked immunosorbent assay (ELISA) (Helico-G) and latex agglutination (Pyloriset) tests. RESULTS: The sensitivity, specificity, and predictive values of histology and CLO-test, compared with culture, ranged from 90% to 97%, regardless of NSAID intake. In the 59 patients not taking NSAIDs Helico-G had a sensitivity of 75% (p < 0.05) and a specificity of 61%; Pyloriset's sensitivity and specificity were, respectively, 63% (p < 0.05) and 67%. In the 75 patients taking NSAIDs the sensitivity of Helico-G was 81% and its specificity 45% (p < 0.05); Pyloriset had a sensitivity of 61% (p < 0.05) and a specificity of 50% (p < 0.05). CONCLUSION: These findings suggest that H pylori is more reliably diagnosed by culture, histology, and CLO-test than by the serological tests used in this study, especially in patients treated with NSAIDs.

Adult

The value of oral antibiotic prophylaxis in biliary tract surgery.

In this study the relationship between the presence or absence of organisms in bile or on closing wound swabs and the subsequent development of wound sepsis was confirmed. There was no significant difference in the incidence of septic complications among three treatment groups in which cefuroxime (iv) and ciprofloxacin (iv or oral) were administered. Consideration of costs attributable to the choice of antibiotic prophylaxis suggests that oral ciprofloxacin in biliary tract surgery may offer significant advantages.

Anti-Bacterial Agents

Macrolides and host defences to respiratory tract pathogens.

An ever-expanding list of macrolides is being developed for therapeutic use. In addition to their direct antimicrobial action, it is being increasingly recognized that these drugs exhibit some degree of immunomodulatory capacity. Some are able to affect polymorphonuclear (PMN) leukocytes, chemotaxis (josamycin, roxithromycin) or respiratory burst (roxithromycin), accumulate within the phagocytic cell (all drugs to a greater or lesser extent) and exhibit intracellular bioactivity (erythromycin, josamycin, roxithromycin). Some of the newer macrolides (rokitamycin and clarithromycin) have not yet been tested in this respect. Nor have the in-vitro effects of the drugs been demonstrated in vivo although indirectly it is well recognized that many of the macrolides are clinically efficacious in the treatment of respiratory tract infections.

Anti-Bacterial Agents

Inhibition of human gastric cyclic AMP production by Helicobacter pylori protein--possible involvement of mucosal prostaglandin E2.

The effect of Helicobacter pylori protein on cAMP and prostaglandin (PGE2) production was studied in incubates of human gastric fundic mucosa. At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg (P less than 0.05) when incubated in H. pylori protein, 155 pmol/kg (P less than 0.006) in histamine, and 23 pmol/kg (P less than 0.05) in histamine plus H. pylori protein. A similar trend was observed at 48 hours. Although H. pylori protein had no direct effect on mucosal PGE2, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE2 and cAMP production. Given the role of cAMP in various physiological responses, these results suggest that H. pylori protein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second messenger. Assuming that PGE2 is involved in mediating such effect, its role would appear to be either partial or indirect.

Bacterial Proteins

Alveolar macrophage chemotaxis in fire victims with smoke inhalation and burns injury.

In vitro migration of alveolar macrophages was studied in 24 fire victims and 19 controls; all subjects were cigarette smokers. Unstimulated (P = 0.01) and stimulated migration towards casein-(P = 0.01) and zymosan-activated serum (P = 0.002) of macrophages from smoke inhalation patients (SI) (n = 19) was increased when compared to control subjects (CS). Migration of alveolar macrophages from patients with burns without smoke inhalation (burns only, BO) was not increased. Patients with smoke inhalation and no burns (smoke only, SO) (n = 9) had increased migration when compared to controls but this was not statistically significant. Patients with smoke inhalation and burns (SB) (n = 10) had increased unstimulated migration (P = 0.01) and increased migration towards casein (P less than 0.005), ZAS (P less than 0.002) and F-met-leu-phe (P less than 0.05) when compared to controls (CS). Lavage fluid from the fire victims displayed chemotactic activity towards normal human neutrophils and its analysis for the components of the complement cascade proved positive (Clq, Clr, Factor B and C3). These data suggest that activation of alveolar macrophages may contribute to the development of pathophysiological changes in patients with smoke inhalation (SI) and particularly those with smoke inhalation and burns (SB).

Burns

New techniques for assessing pathogenicity of quinolone-resistant bacteria.

Ciprofloxacin and ofloxacin-resistant variants of Staphylococcus aureus and Pseudomonas aeruginosa have been compared with their original drug-sensitive progenitor strains with respect to their susceptibility to opsonophagocytosis by human polymorphonuclear leucocytes. For strains exhibiting low level resistance to each quinolone some depression of chemiluminescence (respiratory burst) was recognized whereas for strains exhibiting high level resistance some potentiation of chemiluminescence occurred. There was no difference in terms of the phagocytic ingestion of each of the strains. This study provides only limited evidence to suggest that changes in bacterial virulence are associated with the development of resistance to the quinolone antimicrobials.

Bacteriological Techniques

The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro.

Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications.

Adult

Helicobacter pylori: bridging the credibility gap.

In summary, therefore, there are interesting associations between H pylori, duodenal ulcer, and non-ulcer dyspepsia. In type B gastritis there may be enough evidence to suggest a causal role. The relation between gastritis and upper gastrointestinal symptomatology, however, remains contentious. The relation between H pylori and acid secretion may be more intimate than was previously thought. 'Pylorites' must temper their enthusiasm and provide hard data; 'Schwartzians' must broaden their horizons.

Campylobacter Infections

Changes in alveolar macrophage, monocyte, and neutrophil cell profiles after smoke inhalation injury.

Thirty two fire victims with smoke inhalation, with or without burns, and 26 control subjects had bronchoalveolar lavage performed. Cell yields and differential cell counts were assessed. All patients and controls were cigarette smokers. Patients with smoke inhalation (SI) injury generally showed higher total bronchoalveolar lavage (BAL) cell yields, and this was significant on repeat lavage from 12 patients. The increase was almost entirely due to an increase in the proportion of neutrophils in patients with smoke inhalation alone (S) and those with cutaneous burns as well as smoke inhalation (S + B). On sequential lavage of 12 patients with smoke inhalation (SI) the proportion of neutrophils had increased; this was significantly higher than on initial lavage. Using various macrophage markers, the proportions of macrophage subgroups were determined. There was an increase in UCHM1 and RFD9 positive cells in each subgroup: the increase in UCHM1 positive cells was significant in patients with burns as well as smoke inhalation, and the increase in RFD9 positive cells was significant in patients with smoke inhalation alone. Assessment of the role of such cells in the development of acute lung injury (such as adult respiratory distress syndrome) may be important in our understanding of the mechanisms entailed.

Bronchoalveolar Lavage Fluid

Pathogenicity of Staphylococcus lugdunensis, Staphylococcus schleiferi, and three other coagulase-negative staphylococci in a mouse model and possible virulence factors.

Staphylococcus lugdunesis and Staphylococcus schleiferi, two newly described species, have been isolated from numerous types of human infections. We compared the pathogenicity of 30 strains of S. lugdunensis, S. schleiferi, Staphylococcus epidermidis, Staphylococcus warneri, and Staphylococcus hominis, using a mouse model in which a foreign body preadhered with the test strain was implanted subcutaneously, followed by injection of the test strain. All five species of staphylococci produced abscesses. Staphylococcus epidermidis, S. schleiferi, and S. lugdunensis yielded species means of 76-91% abscess formation; 80-100% of the infected foreign bodies and tissues were culture positive. These three species were more virulent than S. warneri or S. hominis, which produced abscesses in 54 and 65% of mice, respectively; only 10-48% of the infected samples were culture positive. Transmission electron microscopy of pure cultures of selected strains showed that all species possessed glycocalyx. All species produced a variety of possible virulence factors, such as alpha and delta hemolysins, as well as the aggressins lipase and esterase. The production of exoenzymes did not always correlate with virulence as demonstrated by abscess formation in mice.

Abscess

Changes in phagocytic function with glycaemic control in diabetic patients.

Phagocytic function was assessed by serial whole blood chemiluminescence in poorly controlled type 2 (non-insulin dependent) diabetic patients during efforts to improve glycaemic control and compared with a group of well controlled type 1 (insulin dependent) diabetic patients. Chemiluminescence (corrected to a standard polymorphonuclear count) remained below normal (0.15-0.30 photons/second/cell) for most of the type 2 patients until 12 weeks when the value was significantly increased in patients showing improved glycaemic control (mean (range) 0.25 (0.01-0.43) photons/second/cell) compared with those showing no improvement (0.12(0.01-0.31) photons/second/cell). There was a significant inverse correlation of delta HbA1 with delta chemiluminescence. Although mean chemiluminescence for the type 1 diabetic patients was within the normal range, there was a wide scatter of values (0.19 (0.04-0.43) photons/second/cell) and there was no significant difference compared with the final value of type 2 patients with improved control. Glycaemic control is therefore a major determinant of phagocytic function in diabetic patients, but other factors must contribute, particularly in type 1 (insulin dependent) patients.

Adult

Raised titres of anti-klebsiella IgA in ankylosing spondylitis, rheumatoid arthritis, and inflammatory bowel disease.

Serum titres of IgA are raised in ankylosing spondylitis and increased titres of antibodies to klebsiella have also been reported. The humoral response was investigated in ankylosing spondylitis and other inflammatory disorders. IgA antibodies to klebsiella pneumoniae K43 were measured in patients with ankylosing spondylitis, Crohn's disease, ulcerative colitis, and rheumatoid arthritis and in controls. Significantly raised median titres of anti-klebsiella IgA, measured as optical density at 405 nm with an enzyme linked immunosorbent assay (ELISA), were seen among the patients with ankylosing spondylitis (0.7), Crohn's disease (0.8), rheumatoid arthritis (0.6), and ulcerative colitis (0.8) compared with controls (0.4). Activity of disease in ankylosing spondylitis and titres of anti-klebsiella IgA were not correlated. In contrast, titres of anti-klebsiella IgM were significantly lower in patients with ankylosing spondylitis and ulcerative colitis. The increase in the titres of anti-klebsiella IgA may be due to increased permeability of the gut to bacterial antigens, leading to an increased IgA response in the gut mucosa and permitting the release of IgA into the circulation. As the increased antibody titres were seen in Crohn's disease and rheumatoid arthritis as well as in ankylosing spondylitis the response may be nonspecific, occurring because of possible underlying inflammatory bowel disease in these conditions.

Antibodies, Bacterial

The in-vitro assessment of a collagen/vicryl (polyglactin) composite film together with candidate suture materials for potential use in urinary tract surgery. III. Adherence of bacteria to the material surface.

A Collagen/Vicryl (Polyglactin) composite membrane (developed for use in urinary tract surgery) has been incubated in cultures of radioactively labelled urinary tract pathogens vis Escherichia coli, Staphylococcus epidermidis, and Proteus mirabilis for up to 1 h. For comparison, collagen film, Vicryl mesh, and a number of absorbable and non-absorbable sutures were similarly tested. Following incubation, samples were also examined by scanning electron microscopy. Under the experimental conditions employed, only minimal adherence of the micro-organisms to the collagen coated Vicryl mesh, its two individual components, as well as Vicryl and nylon sutures was observed. Significantly greater numbers of bacteria, however, adhered to silk and Chromic Catgut. The results suggest that adherence of microorganisms to the prosthesis even in infected urine is unlikely to develop into a microcolony of bacteria. However, it should be emphasised that great care must be exercised when extrapolating from the in-vitro to the in-vivo situation.

Bacterial Adhesion

The relevance of in vitro measurements of opsonophagocytosis to the study of antibiotic-PMN-bacterium interactions in vivo.

There is increasing evidence that the outcome of therapy of serious bacterial infections especially in the immuno-compromised patient depends to some extent on the efficacy of the host's reticuloendothelial system. The ability of circulating leukocytes to eradicate foci of bacteria can be influenced directly or indirectly by antibiotics. However, the measurement of such an interaction in vivo is difficult and reliance is placed on in vitro studies. Such models only partly mirror the in vivo situation but, nevertheless, their study improves our understanding of the antibiotic-bacterium-leukocyte interaction. Examples will be drawn from studies of the interaction of staphylococci with host defences under in vitro situations resembling tissue abscesses, valvular endocarditis and catheter-associated infections.

Anti-Bacterial Agents

The measurement of C-reactive protein and immune complexes in endocarditis caused by coagulase-negative staphylococci.

Coagulase-negative staphylococci are a major cause of early endocarditis following the insertion of prosthetic heart valves but rarely cause endocarditis in natural valves. From a 2-year prospective study we report seven cases: six with endocarditis related to prosthetic valves and one with endocarditis related to a natural valve. Each isolate of coagulase-negative staphylococcus was identified biochemically (six Staphylococcus epidermidis; one Staphylococcus hominis) and characterised by bacteriophage typing. Six isolates were also examined for slime production and for extracellular toxins and enzymes: all produced toxin but enzyme and slime production was variable. Concentrations of immune complexes and C-reactive protein in the serum were measured in six of the patients. Our results suggest that measuring C-reactive protein may be useful but measuring immune complexes is not helpful and takes more time.

Antigen-Antibody Complex