Cell-material systems for anterior cruciate ligament regeneration.
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Biomedical subjects
Publications and source records attributed to R Warren.
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OBJECTIVE: To assess Filipino, Turkish and Vietnamese women's views about their care during the postnatal hospital stay. DESIGN: Interviews were conducted with recent mothers in the language of the women's choice, 6-9 months after birth, by three bilingual interviewers. PARTICIPANTS: Three hundred and eighteen women born in the Philippines (107), Turkey (107) and Vietnam (104) who had migrated to Australia. SETTING: Women were recruited from the postnatal wards of three maternity teaching hospitals in Melbourne, Australia, and interviewed at home. FINDINGS: Overall satisfaction with care was low, and one in three women left hospital feeling that they required more support and assistance with both baby care and their own personal needs. The method of baby feeding varied between the groups, with women giving some insight into the reason for their choice. A significant minority wanted more help with feeding, irrespective of the method. The need for rest was a recurrent theme, with women stating that staff's attitudes to individual preferences, coupled with lack of assistance, made this difficult. The majority of comments women made regarding their postnatal stay focused on the attitude and behaviour of staff and about routine aspects of care. Issues related to culture and cultural practices were not of primary concern to women. CONCLUSION: Maternity services need to consider ways in which care can focus on the individual needs and preferences of women.
This retrospective analysis of psychological predictors of attendance studied the women from the annual screening arm of the United Kingdom Coordinating Committee on Cancer Research (UKCCCR) trial of annual screening mammography for the early detection of breast cancer. Some women attended screening at the first invitation in year 1 (attenders), others did not attend for screening at any time (non-attenders), whereas a third group delayed attending until year 2 (ambivalent attenders). A total of 147 women were recruited to the study: 80 attenders, 28 non-attenders and 39 ambivalent attenders. It proved extremely difficult to contact non-attenders to take part in the study. Non-attenders were significantly more depressed on the Hospital Anxiety and Depression Scale; had experienced more miscarriages, stillbirths or terminations of pregnancy; were less knowledgeable about mammography; and were displeased to have received an invitation to screening. Whereas non-attenders are unlikely ever to attend breast screening because of their long-standing attitudes and preferred coping styles, ambivalent attenders may become more amenable to screening with the passage of time. In this study such women were persuaded to attend in year 2 with a simple, cost-effective intervention: an additional invitation letter after a year.
In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further.
OBJECTIVES: To assess the effects of mammographic parenchymal patterns on the risk of breast cancer detected at first screen, second screen, and in the interval between these two screens. SETTINGS: A nested case-control study within a screening cohort in East Anglia was designed. The study group comprised 502 patients with cancer at the prevalence screening round, 198 patients with interval cancer, and 175 with cancer at the first incidence screen. These patients were matched with 2601 controls. METHODS: The mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification. Statistical analysis was by conditional logistic regression. RESULTS: Overall, 67% of patients and 59% of controls were considered to have high risk pattern (P2 + DY) mammogram. The risk associated with P2 or DY mammographic patterns compared with N1 was higher for interval cancers (odds ratios (ORs) 2.2 and 2.4 respectively) than for screen detected cancers (ORs 1.7 and 1.1 respectively). For interval cancers in the first 18 months after the last negative mammogram, the risk was particularly high (ORs 3.8 for P2 and 4.1 for DY compared with N1). The high risk associated with P2 and DY patterns was concentrated on invasive ductal grade III cancers (ORs 2.7 and 3.8) rather than grade I or II cancers (ORs 1.6 and 1.2). CONCLUSIONS: The study strongly suggests that screening effectiveness is reduced for high risk parenchymal patterns which are associated with high grade cancers. Changes should aim at improving screening sensitivity for dense parenchymal patterns, and the diagnosis of high grade tumours.
Nine male patients with wide open physes who underwent intra-articular anterior cruciate ligament (ACL) reconstruction using semitendinosus and gracilis tendon grafts passed through the tibial physis and over the top of the femoral condyles were retrospectively reviewed at an average follow-up of 39 months (range: 24 to 72 months). Five patients underwent reconstruction < 6 weeks following injury (range: 11 days to 41 days); the other four underwent reconstruction 2, 3, 5, and 24 months following injury. Seven patients had excellent results and fully returned to their sport. Mean Lysholm score in these patients was 99 (range: 95 to 100), and the mean maximum KT-1000 difference (available for six patients) was 2.8 mm (range: 0 to 5.5 mm). Four of six intact grafts had a mean maximum KT-1000 difference < or = 3.5 mm. Two grafts ruptured and were considered failures (one complete rupture at 10 months and one partial rupture at 3 years). Postoperative height increase averaged 10.7 cm (range: 4 to 22.9 cm). No patient had a clinically significant leg-length discrepancy, angular deformity, or radiographic evidence of physeal injury.
In recent years, expressions of concern about the safety of women in mixed sex wards have been noted. The purpose of this exploratory study was to give hospitalized women with a diagnosis of mental illness the opportunity to describe their experiences in mixed sex wards. A qualitative study, using focus groups, was conducted. The three major themes that emerged from the study were: (i) environment; (ii) gender; and (iii) vulnerability. The study incorporated a feminist and phenomenological perspective. In essence, the study found that although some women had experienced problems with safety, they indicated they would prefer mixed sex to single sex wards.
The tissue-restricted GATA-4 transcription factor and Nkx2-5 homeodomain protein are two early markers of precardiac cells. Both are essential for heart formation, but neither can initiate cardiogenesis. Overexpression of GATA-4 or Nkx2-5 enhances cardiac development in committed precursors, suggesting each interacts with a cardiac cofactor. We tested whether GATA-4 and Nkx2-5 are cofactors for each other by using transcription and binding assays with the cardiac atrial natriuretic factor (ANF) promoter_the only known target for Nkx2-5. Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells. The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension; similarly, a C-terminally extended homeodomain of Nkx2-5 is required for GATA-4 binding. Structure/function studies suggest that binding of GATA-4 to the C-terminus autorepressive domain of Nkx2-5 may induce a conformational change that unmasks Nkx2-5 activation domains. GATA-6 cannot substitute for GATA-4 for interaction with Nkx2-5. This interaction may impart functional specificity to GATA factors and provide cooperative crosstalk between two pathways critical for early cardiogenesis. Given the co-expression of GATA proteins and NK2 class members in other tissues, the GATA/Nkx partnership may represent a paradigm for transcription factor interaction during organogenesis.
BACKGROUND: Dramatic changes in body size and pattern occurred during the radiation of many taxa in the Cambrian, and these changes are best documented for the arthropods. The sudden appearance of such diverse body plans raises the fundamental question of when the genes and the developmental control systems that regulate these designs evolved. As Hox genes regulate arthropod body patterns, the evolution of these genes may have played a role in the origin and diversification of the arthropod body plan from a homonomous ancestor. To trace the origin of arthropod Hox genes, we examined their distribution in a myriapod and in the Onychophora, a sister group to the arthropods. RESULTS: Despite the limited segmental diversity within myriapods and Onychophora, all insect Hox genes are present in both taxa, including the trunk Hox genes Ultrabithorax and abdominal-A as well as an ortholog of the fushi tarazu gene. Comparative analysis of Hox gene deployment revealed that the anterior boundary of expression of trunk Hox genes has shifted dramatically along the anteroposterior axis between Onychophora and different arthropod classes. Furthermore, we found that repression of expression of the Hox target gene Distal-less is unique to the insect lineage. CONCLUSIONS: A complete arthropod Hox gene family existed in the ancestor of the onychophoran/arthropod clade. No new Hox genes were therefore required to catalyze the arthropod radiation; instead, arthropod body-plan diversity arose through changes in the regulation of Hox genes and their downstream targets.
The genes encoding the CS6 colonization factor were cloned from two human enterotoxigenic Escherichia coli strains of different serotypes. The DNA sequences from both clones were nearly identical and contained four open reading frames. Two of them have homology to genes encoding molecular chaperones and ushers found in many other operons encoding colonization factors. The two remaining open reading frames encode two heterologous major subunit proteins which makes CS6 unique because other colonization factors have only one major subunit. Upstream and downstream of the CS6 operon the DNA sequences of the clones diverged abruptly.
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We recently changed from using fine needle aspiration cytology to using core biopsy exclusively in the assessment of screen detected abnormalities. Two hundred and two biopsies (1% of women screened) were performed. Surgical histological confirmation was obtained in 111 patients (101 malignant and 10 benign). The remaining patients were either returned to standard 3-yearly screening or early repeat screening after 1 year. Analysis of the results was performed in accordance with the standards specified in the National Health Service Breast Screening Programme (NHSBSP) Publication Number 22. Absolute sensitivity was 89.3%, complete sensitivity was 93.2%, specificity (including patients undergoing both surgical excision and follow-up) was 88.7%. The predictive value of a positive (malignant) core biopsy result was 100%. The false negative rate was 3.9%. Twelve (5.9%) biopsies were classified inadequate for diagnosis. Core biopsy is a safe and accurate way of assessing screen detected abnormalities and can be used as a substitute for fine needle aspiration cytology with results that exceed the National Health Service Breast Screening Programme target standards, even in the learning phase.
OBJECTIVE: To compare the coronary and cerebral perfusion achieved using a novel method of minimally-invasive, direct cardiac massage to that obtained using bimanual, open-chest cardiac massage. DESIGN: Prospective, controlled animal study with repeated measures. SETTING: University research laboratory. SUBJECTS: Large domestic swine. INTERVENTIONS: Aortic, coronary sinus, jugular venous and pulmonary artery catheters were placed. Following an equilibration period, ventricular fibrillation was induced. After 4 min of untreated ventricular fibrillation, animals underwent bimanual, open-chest cardiac massage (N = 6) or minimally-invasive, direct cardiac massage using a novel device for direct cardiac compression (N = 6). Adrenaline was administered at a dose of 1 mg intravenously every 5 min. MEASUREMENTS: Systemic metabolic parameters, (arterial PO2, PCO2 and lactate concentration) and coronary sinus and jugular venous metabolic parameters (pH, PVO2, SVO2, PVCO2 and lactate concentration) were measured and calculated (coronary sinus/jugular-arterial SVO2, coronary sinus/jugular-arterial PCO2 and lactate differences) at baseline and at 10, 20 and 30 min following induction of ventricular fibrillation. Animals were euthanised after 30 min with no attempt at defibrillation. MAIN RESULTS: Oxygen tension and oxygen saturation of coronary sinus blood declined significantly during the experimental period, but no differences were noted between treatment groups. The coronary sinus-arterial oxygen saturation difference increased during the study with no significant differences between groups. Coronary sinus PCO2 and the coronary sinus-arterial PCO2 difference increased significantly in both experimental groups during cardiac massage. No inter-group differences were noted. A similar relationship was noted in coronary sinus lactate values. The coronary sinus-arterial lactate difference displayed a positive balance at all intervals with no differences noted between group values. The oxygen tension and oxygen saturation of jugular venous blood, were reduced from baseline levels with both treatments. The jugular-arterial oxygen saturation difference increased in both groups compared to baseline values. Between group values were significantly different only at the 20 min interval. Both the jugular venous PCO2 and the jugular-arterial PCO2 gradient were elevated at all intervals, but no inter-group differences were noted. Jugular venous lactate concentration rose steadily with time in both groups. No significant increase in the jugular-arterial lactate gradient was noted at any time point. CONCLUSIONS: Minimally-invasive, direct cardiac massage provides coronary and cerebral perfusion similar to that achieved using standard open-chest cardiac massage. This method may provide a more effective substitute for standard, closed-chest cardiac massage in cases of refractory cardiac arrest.
Autoimmunity may be a pathogenic factor in autism, a behavioral disorder of early childhood onset. Circulating autoantibodies are produced in organ-specific autoimmunity; therefore, we investigated them in the plasma of autistic subjects, mentally retarded (MR) subjects, and healthy controls. Autoantibodies (IgG isotype) to neuron-axon filament protein (anti-NAFP) and glial fibrillary acidic protein (anti-GFAP) were analyzed by the Western immunoblotting technique. We found a significant increase in incidence of anti-NAFP (P = .004) and anti-GFAP (P = .002) in autistic subjects, but not in MR subjects. Clinically, these autoantibodies may be related to autoimmune pathology in autism.
In 3 experiments altitude control was examined as a function of texture type and forward speed. Four texture types were used: grid (rectangular grid with neutral colored cells); dot (small triangles distributed randomly on the ground surface); splay (rows of colored texture parallel to the direction of motion); and depression (rows of colored texture extending perpendicular to the direction of motion). The first 2 experiments required participants to track a constant altitude. Experiment 3 required participants to descend as low as possible without crashing. Results showed an interaction between texture type and forward speed. At low speeds, there was little difference between performance with the depression and splay textures. However, performance with the depression texture deteriorated with increasing forward speeds. Performance with the splay texture was independent of forward speed.
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PURPOSE: A 28-year-old hypertensive professional football player suffered a lacunar stroke. Given the rarity of stroke at this young age, the contributory roles of hypertension and competitive athletics merit consideration. CASE SUMMARY: A 28-year-old defensive lineman, with long-standing, albeit recently well-controlled hypertension, experienced slurred speech and veering to his right after a game. Computerized tomography revealed a small internal capsule infarct. Diagnostic investigation, including coagulation profiling, sickle screen, antiphospholipid antibody, carotid imaging, and echocardiography did not reveal a cause. The patient recovered within days with no residual impairment. DISCUSSION: Despite the extreme blood pressure elevation associated with isometric straining in young athletes, stroke almost never occurs. Vascular changes resulting from chronic hypertension and/or marked volume depletion, and hemoconcentration resulting from restricted salt intake, diuretic use, and heavy sweating, offer the only explanations for this stroke. RELEVANCE: The case suggests physicians should exercise caution in using diuretics and salt-restricted diets to treat hypertensive athletes. Guidelines for treatment are discussed.
Mycobacterium tuberculosis strains resistant to two or more of the first line antituberculosis drugs (MDR) are a serious threat to successful tuberculosis control programmes. For this retrospective study, 85 follow-up drug resistant isolates from 23 patients residing in a community with a high incidence of tuberculosis were collected and the level of in-vitro resistance to antibiotics determined quantitatively. PCR-SSCP and sequencing techniques were used to screen for gene mutations associated with resistance in 31 follow-up samples from a smaller group of eight patients. DNA fingerprint analysis was done on sequential isolates to confirm identity. Although treatment had a profound effect on changes in drug resistance patterns, the MIC for a particular agent remained constant in follow-up isolates. DNA fingerprinting and mutational analysis (14 different loci) showed that the genome of MDR strains of M. tuberculosis is relatively stable during the course of therapy. The rpoB gene was the most frequently mutated structural gene involved in drug resistance and a novel C to T mutation upstream of open reading frame (ORF)1 of the inhA operon was detected. No evidence was found of the presence of strain W (New York) in this group of MDR strains. The results stress the importance of confirming individuality of strains for the accurate calculation of frequencies of particular mutations associated with drug resistance, particularly in a high incidence area. Approximately one-half (47.8%) of the patients had isolates resistant to concentrations just above the critical concentration for isoniazid (MICs of 0.2-5 mg/L). Therefore, these patients and their contacts who develop primary drug-resistant tuberculosis may respond to higher dosages of treatment which could have a considerable impact on the cost and the ease of management of resistant tuberculosis.