Search PubMedSearch

Biomedical subjects

A M Clarke

Publications and source records attributed to A M Clarke.

At least 19 recordsLinked to original sources

Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy.

Helicobacter pylori causes chronic (type B) gastritis. The 'intestinal' form of gastric cancer arises against a background of chronic gastritis, and prospective epidemiological studies have shown that H pylori is a major risk factor for this. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging where there is chronic epithelial cell injury associated with H pylori gastritis. In vitro bromodeoxyuridine labelling of endoscopic antral biopsy specimens was used to measure mucosal cell proliferation in H pylori associated gastritis before and after therapy for H pylori triple infection. Cell proliferation was increased in H pylori associated gastritis patients compared with normal controls and patients with H pylori negative chronic gastritis (p = 0.0001; Tukey's Studentised range). There was no difference in antral epithelial cell proliferation between duodenal ulcer and non-ulcer subjects infected with H pylori (p = 0.62; Student's t test). Antral mucosal cell proliferation fell four weeks after completing triple therapy, irrespective of whether or not H pylori had been eradicated (p = 0.0001). At retesting six to 18 months later (mean = 12 months), however, those in whom H pylori had not been successfully eradicated showed increased mucosal proliferation compared with both H pylori negative subjects at a similar follow up interval and all cases (whether H pylori positive or negative) four weeks after completion of triple therapy (p = 0.024). These findings suggest that H pylori infection causes increased gastric cell proliferation and in this way may play a part in gastric carcinogenesis.

Adult

Cell proliferation in the gastric corpus in Helicobacter pylori associated gastritis and after gastric resection.

Patients who have undergone gastric resection are at higher risk of developing gastric carcinoma than normal subjects, and bile reflux is believed to play a role in carcinogenesis. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. Helicobacter pylori is considered a major risk factor for gastric cancer in the intact stomach. It has been shown previously that antral cell proliferation is increased in H pylori gastritis and falls to normal levels after eradication of the organism. Little is known of corpus cell proliferation in H pylori gastritis or after gastric resection. Using in vitro bromodeoxyuridine labelling of endoscopic biopsy specimens we have found that corpus cell proliferation is increased in H pylori gastritis. Cell proliferation was greater in corpus biopsy specimens of resected stomachs than in H pylori gastritis. Subgroup analysis of patients who had undergone gastric resection indicated that those positive for H pylori had higher levels of cell proliferation than those negative for the organism. These findings provide further evidence that H pylori and bile have a role in gastric carcinogenesis and suggest that their presence has a synergistic effect on gastric epithelial cell proliferation.

Adult

Comparative in vitro activity of FK-037, a new cephalosporin antibiotic.

The in vitro activity of FK-037, a novel parenteral oxime-type cephalosporin, was compared with that of cefepime, cefpirome, ceftazidime, imipenem, and gentamicin against a total of 668 recent clinical isolates. Minimum inhibitory concentrations were determined by a standard agar dilution procedure, and all isolates were tested at two inocula (10(4) and 10(6) colony forming units). FK-037 inhibited 90% of isolates of Escherichia coli, Klebsiella species, Proteus mirabilis, P. vulgaris, Morganella morganii, Serratia marcescens, Providencia stuartii, Citrobacter freundii, Salmonella typhi, Shigella sonnei, Yersinia enterocolitica, Aeromonas species, and Haemophilus influenzae at < or = 1 microgram/ml. FK-037 was less active against Enterobacter species, Acinetobacter species, and Pseudomonas species, requiring 16 micrograms/ml to inhibit 90% of isolates, and was inactive against Xanthomonas maltophilia. FK-037 inhibited 90% of methicillin-susceptible Staphylococcus aureus at < or = 1 microgram/ml and 90% of methicillin-resistant S. aureus at < or = 8 micrograms/ml.

Bacteria

Comparison of labelling by bromodeoxyuridine, MIB-1, and proliferating cell nuclear antigen in gastric mucosal biopsy specimens.

AIMS: To compare proliferating cell nuclear antigen (PCNA) and MIB-1 with bromodeoxyuridine (BrdU) pulse labelling, a specific marker of cell proliferation, in endoscopic gastric biopsy specimens. METHODS: Twenty four biopsy specimens were obtained from 12 patients: 10 antral and eight body specimens were suitable. Each specimen was routinely processed and stained with haematoxylin and eosin. A modified Giemsa stain was used to detect the presence of Helicobacter pylori. Sections of the specimens were labelled with BrdU, MIB-1, and PC10. Gastric mucosa specimens were divided into three zones. The numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone and expressed as a percentage. RESULTS: The proportion of PCNA positive cells (range 0-90%) was much greater in all specimens (10 antrum, eight body). BrdU positive cells were virtually all confined to zone 2 (0-17% cells in this zone were positive) (zone 1 = surface and gastric pit, zone 2 = isthmus, zone 3 = gland base), while PCNA positive cells were present in all three zones (1 = 23-90%, 2 = 43-90%, 3 = 0-74%). Spearman's rank coefficient correlation of 0.57 confirmed that the percentage of positively staining cells varied in the same direction for both PCNA and BrdU (p < 0.001). PCNA, however, was overexpressed in all zones of the gastric epithelium compared with BrdU. In 38 biopsy specimens from 19 patients, of which 14 antrum and 11 body were suitable, the proportion of MIB-1 positive cells (0-59%) was greater than BrdU in most. As with BrdU labelling, the MIB-1 positive cells were confined to zone 2 (zone 1 = 1-11%); zone 2 = 21-59%; zone 3 = 0-13%) and the coefficient correlation for MIB-1 and BrdU was 0.63 (p < 0.001). CONCLUSIONS: MIB-1 accurately reflects the S-phase fraction in gastric mucosa, determined by BrdU labelling in conventionally processed gastric biopsy material. Caution is needed in the interpretation of PCNA labelling detected by PC10, which should not be accepted uncritically as a marker of cell proliferation in paraffin wax embedded material.

Antibodies, Monoclonal

Combined proliferating cell nuclear antigen and morphometric analysis in the diagnosis of cutaneous lymphoid infiltrates.

AIMS: To evaluate the use of morphometry in the diagnosis of benign and malignant cutaneous lymphoid infiltrates; and to determine whether the sensitivity of detection of cutaneous T cell lymphoma (CTCL) could be improved by selectively measuring cells expressing proliferating cell nuclear antigen (PCNA). METHODS: 44 archival biopsy specimens were studied. These included cases of CTCL, non-specific chronic dermatitis, lichen planus and lupus erythematosus. PCNA was identified using a standard immunohistological technique. Reactive cells were identified using automatic colour discrimination, and the size and shape were determined interactively. Similar measurements were made on the total dermal lymphocyte population. RESULTS: There was no significant difference between the proportions of PCNA reactive cells in any of the diseases studied. The PCNA positive lymphocytes in CTCL were larger than those in lupus erythematosus and lichen planus and were more irregular in shape than those in chronic dermatitis. Differences were also seen in the total lymphocyte population. Plotting cell size and shape(fcircle) for PCNA cells together allowed CTCL to be differentiated from the inflammatory disorders with a sensitivity of 80% and a specificity of 93%. This was better than could be achieved using measurements made on the total cell population. CONCLUSIONS: This technique can be partly automated and could be useful in the differential diagnosis of cutaneous lymphoid infiltrates. The result are also of some interest in the further understanding of patterns of cell proliferation in skin associated lymphoid tissue.

Antigens, Neoplasm

Closed intramedullary biopsy for metastatic disease.

The surgical stabilization of metastatic fractures or impending fractures of long bones is recommended with the use of intramedullary nails. While the primary tumour has often been diagnosed previously, there are occasions when the fracture may be the presenting feature of malignancy. In both circumstances surgical oncologists require a histological diagnosis from around the fracture site so that any adjuvant therapy can be planned. Open biopsy is often employed although a closed method has been used by percutaneous puncture. Although intramedullary specimens have been obtained before with long bronchial type biopsy forceps, we report a simple and reliable technique for closed biopsy taken from intramedullary reamings at the time of fracture fixation. Lesions from both the femur and the humerus are amenable to this technique.

Aged

Reconstituted thiopentone retains its alkalinity without bacterial contamination for up to four weeks.

The manufacturers of thiopentone recommend that after reconstitution, it should be kept only for 24 hr to reduce the risk of contamination. However, there are no studies to support this practice and compliance with this recommendation has economic implications. The reasons for discarding a reconstituted bottle of thiopentone are related to concerns about chemical and physical (pH) stability, contamination with infectious agents, and contamination with cellular material. We studied the incidence of bacterial contamination and pH stability of thiopentone in clinical use, as well as the pH stability of thiopentone not in clinical use, and surveyed the eight hospitals affiliated with the University of British Columbia to determine their protocols for thiopental preparation and storage. Cost comparisons were made between our current practice of discarding thiopentone when depleted and the practice of routinely discarding it 24 hr after reconstitution. Samples of thiopentone in clinical use were cultured daily and the pH was measured. The bottles had been in clinical use from 1 to 25 days (mean 4.23 +/- 4.32 SD). Of 106 samples there were no positive bacteriological cultures and there were only minor changes in pH. The telephone survey of the eight hospitals revealed that only one had a policy to discard thiopentone after 24 hr. Cost comparisons indicate that discarding thiopentone 24 hr after reconstitution would result in increased cost. In conclusion, reconstituted thiopentone retains its alkalinity for up to four weeks, and has an acceptably low risk of bacterial contamination for periods beyond 24 hr, therefore thiopentone need not be discarded after 24 hr.

Alkalies

Does plaster immobilization predispose to pulmonary embolism?

Over a 5-year study period, 22 patients with isolated lower limb injuries who were immobilized in a plaster cast developed a pulmonary embolus. This information was not available from orthopaedic audit. Better cross-specialty accounting is required if complications that span different hospital specialties are to be fully elucidated. This problem was heightened by the number of emboli occurring while the patient was being treated as an outpatient.

Adult

Antimicrobial susceptibilities and beta-lactamase characterization of Capnocytophaga species.

Capnocytophaga species have been associated with a wide variety of infections in both immunocompetent and immunocompromised patients. On the basis of data from antimicrobial susceptibility studies, beta-lactam antibiotics have been considered efficacious therapy. Six of 19 isolates from primarily clinical sources across Canada demonstrated beta-lactamase production, and agar dilution susceptibility testing showed broad resistance to beta-lactam antibiotics. For the beta-lactamase producing isolates, clavulanate reduced the MIC of amoxicillin for 90% of the strains tested by 64-fold. Isolates were highly susceptible to clindamycin, imipenem, and ciprofloxacin. Characterization of the beta-lactamases produced by two of these isolates (Van1 and Van2) was performed. Isoelectric focusing revealed an identical isoelectric point of 5.6 for both enzymes, but they had markedly different relative hydrolysis efficiencies, and different conditions were required to extract the enzymes. This study demonstrates the production of different types of beta-lactamases by Capnocytophaga spp. and suggests the need to screen all clinical isolates of Capnocytophaga spp. for the presence of beta-lactamases.

Anti-Bacterial Agents

Chronic microsporidian infection of the nasal mucosae, sinuses and conjunctivae in HIV disease.

A case of chronic infection of the nasal mucosae, sinuses and conjunctivae with a microsporidian parasite in association with HIV infection and immune deficiency is reported. This microsporidian resembles both Encephalitozoon cuniculi and the newly described Encephalitozoon hellem by electron microscopy. This occurred in an adult male resident in the UK with no history of foreign travel. Although there are previous descriptions of conjunctival infections from the USA, this is the first description of infection of the nasal epithelium. Further studies are underway to classify this protozoan.

Adult

Blood loss and transfusion requirements in total joint arthroplasty.

We report a prospective trial of 100 consecutive patients undergoing primary total hip or knee arthroplasty in order to assess their blood transfusion requirements amid recent fears of the transmission of viruses, particularly hepatitis C, from donor to recipient. Of the patients, 84% were transfused one or more units of blood in the perioperative period and the mean percentage blood loss per replacement represented 30% or less of their estimated circulating blood volume. We suggest that with preoperative blood volume calculations and haemoglobin concentrations, a more cautious approach to blood transfusion should be employed when other blood volume expanders would suffice. We believe, firstly, that where blood losses of 30% or less of the blood volume occur, blood transfusion is not always required in patients with high haemoglobin concentrations and large blood volumes. Secondly, cross-matching should be undertaken according to the individual patient's estimated needs, rather than to a group as a whole.

Adult

Therapeutic interchange of cefazolin with metronidazole for cefoxitin.

The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings.

British Columbia

Management of hip posture in cerebral palsy.

Seating arrangements for cerebral palsy children with total body involvement are often unsatisfactory and can pose considerable problems for the multi-disciplinary team. Hip joints at risk of dislocation must be kept in an abducted position in order to minimize pain. A new wheelchair with a barrel-shaped cylindrical seat has been developed which improves the femoral head location and alleviates pain.

Cerebral Palsy

Human ultrasonic speech perception.

Bone-conducted ultrasonic hearing has been found capable of supporting frequency discrimination and speech detection in normal, older hearing-impaired, and profoundly deaf human subjects. When speech signals were modulated into the ultrasonic range, listening to words resulted in the clear perception of the speech stimuli and not a sense of high-frequency vibration. These data suggest that ultrasonic bone conduction hearing has potential as an alternative communication channel in the rehabilitation of hearing disorders.

Adult

Species identification and antibiotic resistance patterns of the enterococci.

One hundred and forty isolates were identified using the GPI Card (Vitek Systems) and a conventional biochemical scheme. Agar dilution susceptibility testing was performed and isolates were screened for beta-lactamase production. The GPI Card was accurate in identifying Enterococcus faecalis, but discrepant results were obtained for seven (29.1%) of the 24 non-Enterococcus faecalis isolates. Ampicillin resistance was present in 2.9% of isolates and there were no beta-lactamase producers. There was no vancomycin resistance but 12.1% of isolates showed high-level resistance to gentamicin.

Ampicillin Resistance