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Biomedical subjects

A P Davies

Publications and source records attributed to A P Davies.

At least 19 recordsLinked to original sources

Biofilm formation in medical device-related infection.

Medical device-associated infections, most frequently caused by coagulase-negative staphylococci, especially Staphylococcus epidermidis, are of increasing importance in modern medicine. Regularly, antimicrobial therapy fails without removal of the implanted device. The most important factor in the pathogenesis of medical device-associated staphylococcal infections is the formation of adherent, multilayered bacterial biofilms. There is urgent need for an increased understanding of the functional factors involved in biofilm formation, the regulation of their expression, and the interaction of those potential virulence factors in device related infection with the host. Significant progress has been made in recent years which may ultimately lead to new rational approaches for better preventive, therapeutic, and diagnostic measures.

Adhesins, Bacterial↗

A rapid single-step multiplex method for discriminating between Trichogramma (Hymenoptera: Trichogrammatidae) species in Australia.

Inaccurate species identification confounds insect ecological studies. Examining aspects of Trichogramma ecology pertinent to the novel insect resistance management strategy for future transgenic cotton, Gossypium hirsutum L., production in the Ord River Irrigation Area (ORIA) of Western Australia required accurate differentiation between morphologically similar Trichogramma species. Established molecular diagnostic methods for Trichogramma identification use species-specific sequence difference in the internal transcribed spacer (ITS)-2 chromosomal region; yet, difficulties arise discerning polymerase chain reaction (PCR) fragments of similar base pair length by gel electrophoresis. This necessitates the restriction enzyme digestion of PCR-amplified ITS-2 fragments to readily differentiate Trichogramma australicum Girault and Trichogramma pretiosum Riley. To overcome the time and expense associated with a two-step diagnostic procedure, we developed a "one-step" multiplex PCR technique using species-specific primers designed to the ITS-2 region. This approach allowed for a high-throughput analysis of samples as part of ongoing ecological studies examining Trichogramma biological control potential in the ORIA where these two species occur in sympatry.

Animals↗

Lipoma arborescens of the knee.

Lipoma arborescens (diffuse articular lipomatosis) is a rare, benign intra-articular lesion of unknown aetiology. It is characterised by villous proliferation of the synovium and diffuse replacement of the subsynovial tissue by mature fat cells. It forms part of the differential diagnosis for a slowly progressive chronically swollen knee. We present a very rare case of bilateral involvement of the knee and discuss the symptoms, diagnosis and treatment of this condition.

Adult↗

Metal-specific differences in levels of DNA damage caused by synovial fluid recovered at revision arthroplasty.

Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used.

Aged↗

An unusual lymphocytic perivascular infiltration in tissues around contemporary metal-on-metal joint replacements.

BACKGROUND: Metal-on-metal bearing surfaces have been reintroduced for use during total hip replacement. To assess tissue reactions to various types of articulations, we studied the histological appearance of periprosthetic tissues retrieved from around metal-on-metal and metal-on-polyethylene total hip replacements and compared these findings with the appearance of control tissues retrieved at the time of primary arthroplasty. METHODS: Periprosthetic tissues were obtained at the time of revision of twenty-five cobalt chromium-on-cobalt chromium, nine cobalt chromium-on-polyethylene, and ten titanium-on-polyethylene total hip arthroplasties. Control tissues were obtained from nine osteoarthritic hips at the time of primary total hip arthroplasty. Each tissue sample was processed for routine histological analysis, and sections were stained with hematoxylin and eosin. Quantitative stereological analysis was performed with use of light microscopy. RESULTS: Tissue samples obtained from hips with metal-on-metal implants displayed a pattern of well-demarcated tissue layers. A prominent feature, seen in seventeen of twenty-five tissue samples, was a pattern of perivascular infiltration of lymphocytes. In ten of the tissue samples obtained from hips with metal-on-metal prostheses, there was also an accumulation of plasma cells in association with macrophages that contained metallic wear-debris particles. The surfaces of tissues obtained from hips with metal-on-metal prostheses were more ulcerated than those obtained from hips with other types of implants, particularly in the region immediately superficial to areas of perivascular lymphocytic infiltration. The lymphocytic infiltration was more pronounced in samples obtained at the time of revision because of aseptic failure than in samples retrieved at the time of autopsy or during arthrotomy for reasons other than aseptic failure. Total-joint-replacement and surface-replacement designs of metal-on-metal prostheses were associated with similar results. Tissue samples obtained from hips with metal-on-polyethylene implants showed far less surface ulceration, much less distinction between tissue layers, no pattern of lymphocytic infiltration, and no plasma cells. The inflammation was predominantly histiocytic. Tissues retrieved from hips undergoing primary joint replacement showed dense scar tissue and minimal inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: The pattern and type of inflammation seen in periprosthetic tissues obtained from hips with metal-on-metal and metal-on-polyethylene implants are very different. At the present time, we do not know the prevalence or clinical implications of these histologic findings, but we suggest that they may represent a novel mode of failure for some metal-on-metal joint replacements.

Biocompatible Materials↗

The optimum knee flexion angle for skyline radiography is thirty degrees.

There is wide variation in practice among orthopaedic surgeons regarding the use of skyline tangential patellar radiographs of the patellofemoral joint in patients with anterior knee pain. Various techniques are available for taking such radiographs and numerous radiologic parameters can be measured from them. There is no information as to which knee flexion angle is superior when taking skyline radiographs. The purpose of the current study was to compare the results of skyline radiographs taken at 30 degrees, 50 degrees, and 90 degrees knee flexion. Sixty-seven knees were studied prospectively. All radiographs were made anonymous and then were studied in random order by two observers. Five recognized patellofemoral parameters were recorded. All the parameters studied were measured most reproducibly when measured from the radiograph taken at 30 degrees knee flexion. The parameters were least reproducible when measured from the radiograph taken at 90 degrees knee flexion. In terms of detecting abnormality of the parameters measured, the radiographs taken at 30 degrees and 50 degrees were similar. The radiograph taken at 90 degrees knee flexion detected the fewest abnormalities. Skyline radiographic examination of the patellofemoral joint should be a mandatory part of the investigation of all knee problems. One radiograph, ideally taken at 30 degrees knee flexion, offers the best means of assessing the patellofemoral joint. There is no benefit to requesting multiple images at different angles of knee flexion.

Adolescent↗

Outbreak of isoniazid resistant tuberculosis in north London.

BACKGROUND: A description is given of a major outbreak of isoniazid monoresistant tuberculosis (TB) chiefly in north London, including prisons. The earliest case was diagnosed in 1995 with most cases appearing after 1999. METHODS: Confirmation of a local cluster of cases was confirmed by restriction fragment length polymorphism (RFLP IS6110) typing or "rapid epidemiological typing" (RAPET). Further cases were found by retrospective analysis of existing databases, prospective screening of new isolates, and targeted epidemiological case detection including questionnaire analysis. RESULTS: By the end of 2001, 70 confirmed cases in London had been linked with a further 13 clinical cases in contacts and nine epidemiologically linked cases outside London. The epidemic curve suggests that the peak of the outbreak has not yet been reached. Cases in the outbreak largely belong to a social group of young adults of mixed ethnic backgrounds including several individuals from professional/business backgrounds. Compared with other cases of TB reported to the enhanced surveillance scheme in London during 1999-2001, the cases are more likely to be of white (26/70 (37%) v 1308/7666 (17%)) or black Caribbean ethnicity (17/70 (24%) v 312/7666 (4%)), born in the UK (41/70 (59%) v 1335/7666 (17%)), and male (52/70 (74%) v 4195/7666 (55%)). Drug misuse and/or prison detention are factors common to many cases. CONCLUSIONS: The investigation of the outbreak revealed significant problems on an individual patient and population based level including difficulties with contact tracing, compliance, and the risk of developing multidrug resistance. This incident has demonstrated the value of molecular strain typing in investigating an extensive outbreak of TB. This is the first documented outbreak involving a UK prison.

Adolescent↗

The radiologic prevalence of patellofemoral osteoarthritis.

The radiographs of 206 knees from 174 consecutive patients were reported blinded regarding joint space narrowing. Minimum joint space was measured using a millimeter ruler on weightbearing posteroanterior and skyline patellofemoral radiographs. Lateral radiographs were reported solely in terms of presence or absence of patellofemoral arthritis. The results showed objective joint space narrowing to less than 3 mm in the patellofemoral compartment of 32.7% of men and 36.1% of women older than 60 years. This high prevalence of patellofemoral disease in men has not been documented before. Arthritic changes occurred in the patellofemoral compartment in isolation in 13.6% of women and 15.4% of men older than 60 years. The lateral radiograph had poor results for detection of patellofemoral osteoarthritis with a sensitivity of 66% and specificity of 83%. The positive predictive value of an abnormal lateral radiograph was 52%. If requests for skyline radiographs had been confined to patients with abnormal patellofemoral joints as assessed on lateral films then 28 normal joints would have been imaged and 14 abnormal joints would have been missed. Osteoarthritis is more common in the patellofemoral joints of men and women than previously documented and only can be properly assessed using a skyline radiograph.

Adult↗

Audit of turnaround times for processing Mycobacterium tuberculosis specimens in a district general hospital.

Automated liquid culture systems, coupled with molecular techniques, have decreased the time required for culture, identification and antibiotic susceptibility testing of Mycobacterium tuberculosis. This audit assessed the turnaround times of a district general hospital (DGH), assisted by the reference laboratory, for processing samples for Mycobacterium tuberculosis. A liquid culture system was in use. The hospital serves an area with a high prevalence of tuberculosis. Request forms and reference laboratory reports were examined for every new laboratory diagnosis of tuberculosis in 2000. Time to result was taken as time from receipt of specimen in the laboratory to date of reporting by reference laboratory. Seventy-two new cases of tuberculosis were culture positive in 2000. Median time to identification was 21.5 days and to antibiotic susceptibility results was 35 days. With liquid culture systems, acceptable turnaround times for processing mycobacteria are achievable, but in many DGHs this equipment is not available.

Cell Culture Techniques↗

Calcaneal compartment syndrome after tibial fractures.

Compartment syndrome of the newly discovered calcaneal compartment of the foot is a theoretical possibility following tibial fracture due to the communication with the deep posterior compartment of the calf. Forty-nine patients were reviewed at least 18 months after open or closed tibial shaft fractures treated with tibial nailing in order to determine the prevalence of foot deformities secondary to previously undetected calcaneal or leg compartment syndromes. Ankle movements, foot height, length of feet and degree of clawing of the toes were all measured and compared with the unaffected opposite side. None of the patients complained of any symptoms from their feet and none had any significant foot deformities. Calcaneal compartment syndrome is rare after tibial fracture and routine measurement of calcaneal compartment pressures after such injuries is not indicated.

Bone Nails↗

Comparison of fitness of two isolates of Mycobacterium tuberculosis, one of which had developed multi-drug resistance during the course of treatment.

OBJECTIVES: We report the cases of two patients, brother and sister, both with pulmonary tuberculosis. Both patients complied poorly with treatment. One developed multi-drug resistant disease, whilst the other did not. We aimed to show that the two infecting strains were the same, and then to compare the fitness of the resistant strain to that of the sensitive strain. METHODS: The isolates were typed by RFLP. The fitness of the multi-drug resistant tuberculosis strain was determined by calculating the ratio of generation produced by the drug-resistant and a drug-susceptible strain in a mixed culture. The number of bacteria present in this broth culture was estimated using the Miles and Misra technique. The number of drug-resistant bacteria present was determined by inoculating aliquots of broth onto Middlebrook 7H10 agar with 5mg/l rifampicin. RESULTS: The infecting strain of Mycobacterium tuberculosis was shown to be the same on RFLP typing in both cases. It was found that the multi-drug resistant organism had decreased fitness compared to the sensitive organism. CONCLUSION: The decreased relative fitness of the resistant strain implies a physiologic cal cost for the development of drug resistance.

Antitubercular Agents↗

Comparison of phenotypic and genotypic methods for pyrazinamide susceptibility testing with Mycobacterium tuberculosis.

Mycobacterium tuberculosis converts pyrazinamide to its active form by using the enzyme pyrazinamidase. This enzyme is coded for on the pncA gene, and mutations in the pncA gene result in absence of active enzyme, conferring resistance to the drug pyrazinamide. We investigated 27 strains of Mycobacterium tuberculosis suspected of being multidrug resistant. Each isolate was tested for susceptibility to pyrazinamide by the BACTEC 460TB method, and 19 were pyrazinamide resistant. The presence of active pyrazinamidase enzyme was sought by using the Wayne assay, which was positive in all of the sensitive isolates and four of the resistant isolates. The pncA gene was amplified by PCR, and mutations were sought by single-strand conformation polymorphism (SSCP) analysis. We identified four isolates which were phenotypically resistant to pyrazinamide, but which had active pyrazinamide enzyme on the Wayne assay and normal pncA gene SSCP. MICs measured by BACTEC 460TB and susceptibility testing at a lower pH of 5.5 confirmed genuine resistance. The pncA gene was sequenced in these four isolates and found not to have any mutations. This implies that an alternative mechanism of resistance exists in these strains. We conclude that genotypic assessment of pyrazinamide resistance is unreliable, because it depends on the identification of a single resistance mechanism. Phenotypic methods such as the BACTEC 460TB technique remain the best methods for pyrazinamide susceptibility testing.

Amidohydrolases↗

The sulcus angle and malalignment of the extensor mechanism of the knee.

Anterior knee pain due to dysplasia of the extensor mechanism is common. We have studied 137 knees (103 patients) in order to identify a rapid and reproducible radiological feature which would indicate the need for further analysis. Overall, 67 knees (49%) had at least one radiological abnormality; 70 (51%) were considered normal. There were five cases of Dejour type-3 dysplasia of the femoral trochlea, nine of type-2 and 12 of type-1. There were 49 cases of patella alta and five of patella infera. Four knees had an abnormal lateral patellofemoral angle (patellar tilt), and in 15 knees there was more than one abnormality. Classification of trochlear dysplasia was difficult and showed poor reproducibility. This was also true for the measurement of the lateral patellofemoral angle. Patellar height was more easily measured but took time. The sulcus angle is an easily and rapidly measurable feature which was reproducible and was closely related to other features of dysplasia of the extensor mechanism. The finding of a normal sulcus angle suggested that seeking other radiological evidence of malalignment of the extensor mechanism was unlikely to reveal additional useful information. The severity of other features of dysplasia of the extensor mechanism correlated with increasing sulcus angle.

Adolescent↗

Screening for ovarian cancer: a pilot randomised controlled trial.

BACKGROUND: The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography. METHODS: Postmenopausal women aged 45 years or older were randomised to a control group (n=10,977) or screened group (n=10,958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8.8 mL or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers). FINDINGS: Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had false-positive screening results. The positive predictive value was 20.7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (p=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10,977 vs nine of 10,958, relative risk 2.0 [95% CI 0.78-5.13]). INTERPRETATION: These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible and justify a larger randomised trial to see whether screening affects mortality.

CA-125 Antigen↗

Expanding mesh stent in the emergency treatment of Boerhaave's syndrome.

Boerhaave's syndrome, or spontaneous esophageal perforation, is a life threatening condition demanding early diagnosis and rapid aggressive management to prevent fulminant mediastinitis and death. We describe a patient treated in an emergency situation with an expanding esophageal mesh stent to bridge the esophageal rent together with chest and mediastinal drainage, resulting in complete recovery and return to the community. We also describe the partial recovery of the stent in the convalescent period.

Aged↗

Length of time to laboratory diagnosis of Mycobacterium tuberculosis infection: comparison of in-house methods with reference laboratory results.

OBJECTIVES: To audit the time taken to obtain laboratory confirmation of infection with Mycobacterium tuberculosis using in-house methods of polymerase chain reaction (PCR) and culture and referral to a reference laboratory. METHODS: Retrospective collection of data from laboratory records covering a period of 1 year. RESULTS: Median time to microbiological diagnosis of a new infection using the in-house services in addition to the reference laboratory was 22.0 days. Using reference laboratory results alone, median time to diagnosis would have been 61.5 days. CONCLUSIONS: Development of on-site laboratory facilities to identify Mycobacterium tuberculosis can reduce the time to its identification by almost two-thirds.

Clinical Laboratory Techniques↗

Plain radiography in the degenerate knee. A case for change.

We took posteroanterior weight-bearing radiographs, both with the joint fully extended and in 30 degrees of flexion, in a consecutive series of 50 knees in 37 patients referred for the primary assessment of pain and/or stiffness. These radiographs were reported 'blind' both by an orthopaedic surgeon and a radiologist. Direct measurement of the joint space, together with grading of the severity of erosion according to the Ahlback criteria, was undertaken. Any other abnormality present was also documented. The radiographs of the knees in 30 degrees of flexion consistently showed more advanced erosion in both the medial (p = 0.001) and the lateral (p = 0.0001) tibiofemoral compartments, when compared with those of knees in full extension. The Ahlback classification of 25 joints was altered, in some cases by several grades, by the flexed position of the joint. In every case in which another abnormality was identified on the radiograph in full extension, it was also noted on that of the knee in 30 degrees of flexion. In a further four cases, additional pathology could only be seen in the flexed knee. Every patient was able to complete the radiological examination without difficulty. Our study supports the adoption of a weight-bearing view in 30 degrees of flexion as the standard posteroanterior radiograph for the assessment of tibiofemoral osteoarthritis in patients over 50 years of age.

Aged↗

Haemophilus paraphrophilus; a rare cause of intracranial abscess.

We report a case of a 42-year-old man man who presented with neurological symptoms and was found to have an intracranial abscess. A stereotactic aspiration of the abscess yielded a pure growth of Haemophilus paraphrophilus. The patient responded to treatment with cefotaxime. We postulate the mechanism of infection in this patient.

Adult↗