The majority of patients return to athletic activity following biceps tenodesis.

PURPOSE: Biceps tenodesis is widely used as a primary treatment for long head of the biceps brachii pathology and superior labral anterior and posterior (SLAP) lesions. However, rates and timing of full return to sports (RTSs)/duty have not been systematically analysed. This systematic review examines the literature to ascertain the rate and timing of return to athletic activity, and the availability of specific criteria for safe return to atheletic activity following the biceps tenodesis. METHODS: Based on PRISMA guidelines, this systematic review utilised the EMBASE, MEDLINE, and The Cochrane Library Databases. Eligible for inclusion were clinical studies reporting on return to athletic activity following biceps tenodesis. Statistical analysis was performed using SPSS. RESULTS: This review identified 17 studies including 374 cases meeting the inclusion criteria. The majority of patients were men 260 (69.7%), with an median age of 42.2 years (range 16-88) and a mean follow-up of 37.4 months. The overall rate of RTS was 217/269 (80.7%), with 43/59 (72.9%) returning to the same level. In overhead athletes, the overall rate of return to play was 39/49 (79.6%). Among military personnel, the overall rate of return to duty was 61/74 (82.4%). The average time to RTS was 5.4 (range 3-11) months. 10 (58.8%) Studies reported a recommended time window within which patients were allowed to return to full activity. Specific criteria for return to play were not reported in any of the identified studies. CONCLUSION: While overall rate of return to athletic activity was reportedly high following biceps tenodesis, one in four patients were not able to resume athletic activity at the same level. At present, there is no objective assessment of when patients can return to full activity reported in the literature. LEVEL OF EVIDENCE: IV.

A multistage mixed methods study protocol to evaluate the implementation and impact of a reconfiguration of acute medicine in Ireland's hospitals.

BACKGROUND: To address deficits in the delivery of acute services in Ireland, the National Acute Medicine Programme (NAMP) was established in 2010 to optimise the management of acutely ill medical patients in the hospital setting, and to ensure their supported discharge to primary and community-based care. NAMP aims to reduce inappropriate hospital admissions, reduce length of hospital stay and ensure patients receive timely treatment in the most appropriate setting. It does so primarily via the development of Acute Medical Assessment Units (AMAUs) for the rapid assessment and management of medical patients presenting to hospitals, as well as streamlining the care of those admitted for further care. This study will examine the impact of this programme on patient care and identify the factors influencing its implementation and operation. METHODS: We will use a multistage mixed methods evaluation with an explanatory sequential design. Firstly, we will develop a logic model to describe the programme's outcomes, its components and the mechanisms of change by which it expects to achieve these outcomes. Then we will assess implementation by measuring utilisation of the Units and comparing the organisational functions implemented to that recommended by the NAMP model of care. Using comparative case study research, we will identify the factors which have influenced the programme's implementation and its operation using the Consolidated Framework for Implementation Research to guide data collection and analysis. This will be followed by an estimation of the impact of the programme on reducing overnight emergency admissions for potentially avoidable medical conditions, and reducing length of hospital stay of acute medical patients. Lastly, data from each stage will be integrated to examine how the programme's outcomes can be explained by the level of implementation. DISCUSSION: This formative evaluation will enable us to examine whether the NAMP is improving patient care and importantly draw conclusions on how it is doing so. It will identify the factors that contribute to how well the programme is being implemented in the real-world. Lessons learnt will be instrumental in sustaining this programme as well as planning, implementing, and assessing other transformative programmes, especially in the acute care setting.

Decisions on repositioning of intruded permanent incisors; a review and case presentation.

BACKGROUND: Traumatic intrusion is a luxation type of injury where the tooth is displaced along the axis of the tooth, into the alveolus. This injury is regarded as serious because of the tissue damage that it causes. The traumatic movement is associated with severe damage to the periodontal ligament, pulpal tissue, root and alveolar socket. Despite its severity, the rare occurrence of this injury in permanent teeth has resulted in limited studies of immature and mature permanent incisors. The purpose of this paper is to review this luxation injury of permanent immature incisors, and to describe its diagnosis, treatment and management. In particular, we describe the repositioning strategies used in cases of intrusion injury. These include (i) monitoring spontaneous re-eruption, (ii) active orthodontic repositioning and (iii) surgical repositioning. Firstly, monitoring spontaneous re-eruption is observing and waiting for the intruded tooth to return to its original position. This process is not a normal developmental eruption and the outcome is not always predictable, nor is the time needed for this to happen. Secondly, active orthodontic repositioning is used to describe the process of rapidly moving the intruded tooth to its original position with the aid of an orthodontic appliance. Active orthodontic repositioning is often misunderstood as normal orthodontic movement. Orthodontic movement allows for periodontal ligament remodelling, using light intermittent forces. In contrast the active orthodontic repositioning used to move intruded incisors is rapid, and the primary aim is to achieve correct tooth position as rapidly as possible. Thirdly, surgical repositioning uses surgical intervention to bring the tooth back to its original position. A case of an intruded immature permanent incisor is presented, with a particular emphasis on these critical decisions on repositioning and showing the use of the three modalities of treatment in sequence, in order to achieve an outcome.

False-negative MRI breast screening in high-risk women.

AIM: To determine the frequency of and reasons for false-negative breast magnetic resonance imaging (MRI) examinations in high-risk women undergoing annual screening. MATERIALS AND METHODS: The family history clinic database was interrogated and women at high risk of breast cancer who had undergone screening MRI and been diagnosed with breast cancer within 2 years of the MRI examination were identified. All available MRI examinations were reviewed and classified by two radiologists. RESULTS: Of 32 women diagnosed with breast cancer, 23 had MRI images available for review. Fourteen were diagnosed at MRI, four at interim mammography, two symptomatically, one incidentally on ultrasound, and two at risk-reducing mastectomy. Ten women (43%) had potentially avoidable delays in diagnosis. The preceding MRIs were classified as false-negative screens in five women (one prevalent, four incident), false-negative assessment in seven and minimal signs in three (three women were assigned dual classifications). Common reasons for diagnostic delay included small enhancing masses that were overlooked, areas of non-mass enhancement that showed little or no change between screens, false reassurance from normal conventional imaging at assessment, and overreliance on short-interval repeat MRI. CONCLUSION: Small enhancing foci, masses, and areas of segmental non-mass enhancement are common MRI features of early breast cancer. Lack of change of non-mass enhancement on serial examinations does not exclude malignancy. Double reading of both screening and assessment examinations is recommended. Ready access to MRI biopsy is essential. Short-interval repeat MRI should be limited to reassessing low suspicion areas likely to be benign glandular enhancement. Annual mammography remains important in these women.

Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality.

BACKGROUND: The addition of annual MRI screening to mammography has heightened optimism that intensive screening along with improved treatments may substantially improve life expectancy of women at high risk of breast cancer. However, survival data from BRCA2 mutation carriers undergoing intensive combined breast screening are scarce. METHODS: We have collated the results of screening with either annual mammography or mammography with MRI in female BRCA2 mutation carriers in Manchester and Oslo and use a Manchester control group of BRCA2 mutation carriers who had their first breast cancer diagnosed without intensive screening. RESULTS: Eighty-seven BRCA2 mutation carriers had undergone combined (n = 34) or mammography (n = 53) screening compared to 274 without such intensive screening. Ten year breast cancer specific survival was 100 % in the combined group (95 % CI 82.5-100 %) and 85.5 % (95 % CI 72.6-98.4 %) in the mammography group compared to 74.6 % (95 % CI 66.6-82.6 %) in the control group. Better survival was driven by lymph node status (negative in 67 % of screened vs 39 % of unscreened women; p < 0.001) and a significantly greater proportion of intensively screened women had invasive breast cancers <2 cm at diagnosis (74.6 % vs 50.4 %; p = 0.002). CONCLUSION: Intensive combined breast cancer screening with annual MRI and mammography appears to improve survival from breast cancer in BRCA2 mutation carriers. Data from larger groups are required to confirm the effectiveness of combined screening in BRCA2 carriers.

A study of primary teeth restored by intracoronal restorations in children participating in an undergraduate teaching programme at Cork University Dental School and Hospital, Ireland.

AIM: To study the outcomes for restored primary molar teeth; to examine outcomes in relation to tooth type involved, intracoronal restoration complexity and to the material used. DESIGN: Retrospective study of primary molar teeth restored by intracoronal restorations. A series of restored primary molar teeth for children aged 6-12 years was studied. The principal outcome measure was failure of initial restoration (re-restoration or extraction). Three hundred patient records were studied to include three equal groups of primary molar teeth restored with amalgam, composite or glass ionomer, respectively. Restorative materials, the restoration type, simple (single surface) or complex (multi-surface) restoration, and tooth notation were recorded. Subsequent interventions were examined. Data were coded and entered into a Microsoft Excel database and analysis undertaken using SPSS v.18. Statistical differences were tested using the Chi square test of statistical significance. RESULTS: Of the 300 teeth studied, 61 restoration failures were recorded with 11 of those extracted. No significant differences were found between outcomes for upper first, upper second, lower first or lower second primary molars. Outcomes for simple primary teeth restored by intracoronal restorations were significantly better than those for complex intracoronal restorations (P = 0.042). Teeth originally restored with amalgam accounted for 19.7% of the 61 failures, composite for 29.5%, while teeth restored with glass ionomer represented 50.8% of all restoration failures. The differences were significant (P = 0.012). CONCLUSIONS: The majority (79.7%) of the 300 restored primary teeth studied were successful, and 3.7% teeth were extracted. Restorations involving more than one surface had almost twice the failure rate of single surface restorations. The difference was significant. Significant differences in failure rates for the three dental materials studied were recorded. Amalgam had the lowest failure rate while the failure rate with glass ionomer was the highest.

Impact of full-field digital mammography on pre-operative diagnosis and surgical treatment of mammographic microcalcification.

Accurate pre-operative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or invasive breast cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite correct pre-operative diagnosis of MM, 26 % require second therapeutic operations to achieve surgical clearance. Theoretically, improved conspicuity of malignant MM using digital mammography could improve diagnostic work-up and improve surgical outcomes for MM. To determine the impact of full-field digital mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV) of biopsy of MM and surgical management of MM, screening and symptomatic cases with MM (n = 1,479) were reviewed for women imaged between August 2007 and March 2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged between April 2010 to March 2012 (n = 768). Demographic information including pre and postoperative diagnosis, and number and types of surgical procedures were recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p < 0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %, p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative diagnosis of MM using digital mammography reduced second therapeutic operations but increased mastectomy rate in larger cancers over two centimetres. This will increase concerns about treatment of lesions detected in the screening programme with widespread use of digital mammography.

Evaluation of the quality of information online for arthroscopic Bankart repair.

PURPOSE: The purpose of this study was to evaluate the quality and readability of information online for patients searching terms related to arthroscopic Bankart repair (ABR). METHODS: Google, Yahoo and Bing were searched with terms related to ABR. The quality of information was assessed using the Journal of the American Medical Association (JAMA) Benchmark criteria, DISCERN Score, and the Flesch-Kincaid Reading Ease & Grade Level. The presence of the HONcode marker was noted. Additionally, we used a scoring system specific to content relating to the ABR (AB score), a 1-20 Likert scale. Websites were also categorised according to the source: academic institution, physician, allied healthcare, commercial, media or social media. Statistical analysis was performed using GraphPad Prism. RESULTS: Ninety-six unique websites were evaluated, with the most common website category being physician websites (52) and academic institution websites (24). There were nine websites with the HONcode marker. The average JAMA Benchmark criteria score was 1.95 (1-4), the average DISCERN score was 48.8 (20-78), with an average Flesch-Kincaid reading ease of 50.9 (11-96) and grade level of 8 (1-18). The average AB score was 5.9 (0-18), and there was a strong correlation with a higher DISCERN score (r=0.57), but not JAMA score (r=0.18) or Flesch-Kincaid grade (r=0.16). Websites with the HONcode marker did not score higher in any criteria than those without it (p>0.05). The quality of information on physician websites was better than (statistically insignificant) non-physician websites; however, the readability of information in the former was poorer (statistically significant) than the latter. CONCLUSION: There was wide variability in the quality and readability online of the information on ABR, and the AB scoring system was shown to correlate strongly with increased quality.

The role of Platelet Rich Plasma and other orthobiologics in bone healing and fracture management: A systematic review.

BACKGROUND: Treatment of large bone defects and fracture healing complications (delayed and non-union) presents a substantial challenge for orthopaedic surgeons. Given that bone healing requires mechanical stability as well as a favourable biological microenvironment, orthobiologics such as Platelet-Rich Plasma (PRP) may have a significant clinical role to play. AIMS: To perform a systematic review of the available literature to assess the clinical effect of PRP, with or without other orthobiologics, on bone healing. METHOD: Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of any evidence, assessing effect of PRP with or without other orthobiologics on bone healing, were included. A qualitative analysis was carried out on the clinical and radiological outcomes reported. RESULT: 27 articles with 1631 patients (mean age = 43.56, 57.1% male, mean follow-up = 17.27 months) were included in the qualitative. Of the 27 studies, 13 dealt with fracture complications (delayed or non-unions), 7 with acute fracture healing, 4 with tibial osteotomies and lengthening procedures and 3 with lumbar spine pathology. 18/27 studies showed a clinical benefit of PRP, 8/27 showed no significant effect, and 1/27 showed a worse outcome with PRP. CONCLUSION: Our review suggests PRP may play a clinical role in bone healing but further randomised controlled trials (RCTs) using standardised outcomes should be performed to establish its efficacy.

B cell activation and the establishment of Epstein-Barr virus latency.

Linear EBV genomes undergo a transition to the circular form characteristic of latency by 16-20 h post-infection. This transition requires that the infected cells be activated to the G1 stage of the cell cycle. Cellular proliferation and expression of the activation marker CD23 were not required. Nevertheless, 36 h post-infection, only cells expressing CD23 contained covalently closed, circular episomes (CCC), at an average of one copy per cell. Since the presence of CD23 at this time is predictive that a cell will immortalize, we suggest that the presence of CCC is required for CD23 expression and subsequent immortalization. The one CCC present in each CD23+ cell did not undergo amplification until well after the cells had acquired all of the characteristic phenotypic markers of immortalization. Therefore, while amplification is not necessary for proliferation and immortalization, circularization of a single genome is crucial to the establishment and maintenance of latency by EBV.

Is it safe for patients to drive after intra-articular knee injection?

BACKGROUND: Intra-articular knee injection is a central component in the current management of knee pain. While this is a routinely performed outpatient procedure, institutional policies for driving post injection differ. This study examines brake response times (BRTs) before and after intra-articular knee injection. Our hypothesis is that BRTs would not significantly differ and thus patients driving ability/safety is unaffected. METHODS: Forty-five patients previously listed for right intra-articular knee injection were prospectively evaluated. Patients underwent baseline assessment of BRT prior to injection. All patients received 10 ml of fluid consisting of one milliliter of 10 mg/ml triamcinolone mixed with nine milliliters of 0.5% levobupivacaine. BRT was re-examined on the same day prior to discharge home. Pre- and post-injection BRTs were examined using the same machine and assessor. RESULTS: The mean age of the cohort was 64.0 ± 12.4 and compromised of 37.8% males. There was no significant difference in the mean pre- and post-injection braking time (0.83 ± 0.29 vs 0.78 ± 0.30 s, p = .42), or in the rate of failed braking time (11.1% vs 6.7%, p = .46). CONCLUSION: This study found that BRT did not significantly differ before and after the intra-articular injection, nor did it cause an increased number of patients failing their BRTs. These findings suggest patients should not be prevented from driving after intra-articular knee injection.

Provision of information on regulatory authorities' websites.

BACKGROUND: Several organizations have raised concerns about the excessive secrecy maintained by regulatory authorities around the world, in particular in the European Union, France, UK, Canada and Australia. However, limited research has assessed the provision of information by regulatory authorities. This study aimed to assess the type and availability of information provided on the regulatory authorities' websites. METHODS: Regulatory authorities' websites in six countries (USA, Canada, UK, France, Australia and New Zealand) and at the European level (European Medicines Evaluation Agency) were surveyed by two reviewers between October 2005 and March 2006. The survey instrument included 16 criteria organized in 3 domains: information on marketed drugs, information on assessment of drugs and information on drug safety. RESULTS: There was a great variability in the level of information provided. Several medicine agencies did not provide basic information on marketed drugs, such as the summary of products' characteristics. Information on registration dossiers was scant on most websites except that of the US Food and Drug Administration. The European Medicines Evaluation Agency, the French agency and the Canadian agency released public assessment reports that contained only summarized information of registration data. Only one country, Canada, provided full access to pharmacovigilance data. The periodic safety update reports that companies have to provide regularly to regulatory authorities were not available in any country. CONCLUSION: Information on which regulatory authorities base their decisions for licensing new drugs and the rationales behind these decisions were often not publicly available.

Effective Treatment of Veterans With PTSD: Comparison Between Intensive Daily and Weekly EMDR Approaches.

The effectiveness of EMDR therapy in treating veterans diagnosed with PTSD was evaluated in this study using two treatment formats: intensive daily EMDR treatment provided twice a day during a 10-day period and a second format of one session each week. The study used archived outcome data previously collected and stored at Soldier Center. Both formats provided 18-20 treatment sessions of EMDR therapy to veterans diagnosed with PTSD that included dissociative exhibitions and moral injury issues. Questions addressed included: (1) does EMDR therapy administered twice daily ameliorate veterans' PTSD symptoms; (2) does EMDR therapy administered twice daily provide equivalent outcome results as EMDR therapy administered weekly for 18-20 sessions; and (3) does the treatment outcome persist. The effectiveness of the weekly treatment group was also evaluated. Both groups' results were assessed at pre-treatment, post-treatment and 1-year follow-up. The results indicated that both weekly treatment and intensive daily treatment groups produced statistically significant treatment effects (p < 0.001) that were maintained at 1-year follow-up. The10-day EMDR intensive daily treatment (EMDR therapy twice a day for 10 days) produced a similar outcome as to that of the weekly treatment with a 1-year follow-up. Results support the effectiveness of EMDR therapy when offered in both weekly treatment format as well as the intensive 10-day format on an outpatient basis. While recognizing the limitations of this study the results are significant to warrant additional research.

Juice Clarification with Pectinase Reduces Yeast Assimilable Nitrogen in Apple Juice without Affecting the Polyphenol Composition in Cider.

The term "cider" refers to the fermented beverage produced from apples. The rapid growth in the cider industry coupled with the prominence of traditional, or craft, approaches emphasizes the need for research on cider production. A common problem in ciders is the production of sulfur off-aromas by yeast during fermentation. Prefermentation juice clarification has the potential to reduce the occurrence of unwanted sulfur off-aromas. Concerns that prefermentation juice clarification will reduce the yeast assimilable nitrogen (YAN) and polyphenols in the juice have limited the application of this practice by cider makers. In this study, 3 clarification methods were applied to 'York' apple juice, that is, static settling, centrifugation, and pectinase. Raw (control) and clarified juice were fermented to cider, and the impact of clarification on the physicochemical parameters, amino acids and polyphenol content of the juice and cider was assessed. Juice clarification by pectinase decreased YAN by 50%, while static settling and centrifugation increased the concentration of most amino acids by 83%. All clarification treatments lowered the concentration of total polyphenols in the juice (from 60% to 30%, P < 0.05) and affected the individual polyphenols in the juice but these changes were not evident in the ciders. These findings demonstrate that prefermentation juice clarification results in changes in the chemistry profiles of apple juice. These changes were however not evident in the ciders. This approach therefore has the potential to limit the production of sulfur off-aromas during cider production without adverse effects on quality. PRACTICAL APPLICATION: Clarification of apple juice changes polyphenol and nitrogen contents, factors known to affect cider quality. However, these differences in the chemical profile of apple juice may not be reflected in the finished ciders. These findings demonstrate that juice clarification can be employed in cider making without affecting the quality. Cider makers should not assume that changes in apple juice imparted by clarification will be reflected in the finished ciders. Outcomes should be measured in finished ciders, rather than juice to accurately evaluate effects of the processing steps on quality.

Germ line maintenance of the pseudogene donor pool for somatic immunoglobulin gene conversion in chickens.

Somatic immunoglobulin diversity is generated in avian species by sequential gene conversion of variable (V) gene segments of the immunoglobulin heavy- and light-chain loci during B-cell development. The germ line pools of donor sequence information for somatic V-region gene conversion are found in families of V pseudogenes, located 5' of the single functional V gene of each locus. The sequence relationships among the pseudogenes (psi VL) and functional VL1 gene of the chicken light-chain alleles in three inbred strains were compared to determine the extent of diversity within the germ line pseudogene cluster. Numerous differences were observed. For example, compared with the previously reported CB allele and the G4 allele, the S3 allele contains two intact pseudogenes between psi VL16 and psi VL18. These two adjacent psi VL gene segments (psi VL17a and psi VL17b) could have given rise to the psi VL17 segment of the G4 and CB alleles by homologous recombination. The majority of other sequence polymorphisms among the psi VL alleles appear to be the result of meiotic gene conversion. The incidence of untemplated mutations within psi VL segments is significantly lower than the incidence of mutation within the pseudogene flanking regions. Together with the observations that most psi VL segments have open reading frames and lack stop codons, these data support the hypothesis that the psi VL cluster resembles a functional multigene family maintained by evolutionary selection for its functional role in generating somatic antibody diversity. Meiotic gene conversion events within the psi VL cluster serve both to introduce diversity by the exchange of short segments between family members and to prevent the accumulation of random mutations.

Dual polarisation interferometry characterisation of DNA immobilisation and hybridisation detection on a silanised support.

Dual polarisation interferometry is an analytical technique that allows the simultaneous determination of thickness, density and mass of a biological layer on a sensing waveguide surface in real time. We evaluated, for the first time, the ability of this technique to characterise the covalent immobilisation of single stranded probe DNA and the selective detection of target DNA hybridisation on a silanised support. Two immobilisation strategies have been evaluated: direct attachment of the probe molecule and a more complex chemistry employing a 1,2 homobifunctional crosslinker molecule. With this technique we demonstrate it was possible to determine probe orientation and measure probe coverage at different stages of the immobilisation process in real time and in a single experiment. In addition, by measuring simultaneously changes in thickness and density of the probe layer upon hybridisation of target DNA, it was possible to directly elucidate the impact that probe mobility had on hybridisation efficiency. Direct covalent attachment of an amine modified 19 mer resulted in a thickness change of 0.68 nm that was consistent with multipoint attachment of the probe molecule to the surface. Blocking with BSA formed a dense layer of protein molecules that absorbed between the probe molecules on the surface. The observed hybridisation efficiency to target DNA was approximately 35%. No further significant reorientation of the probe molecule occurred upon hybridisation. The initial thickness of the probe layer upon attachment to the crosslinker molecule was 0.5 nm. Significant reorientation of the probe molecule surface normal occurred upon hybridisation to target DNA. This indicated that the probe molecule had greater mobility to hybridise to target DNA. The observed hybridisation efficiency for target DNA was approximately 85%. The results show that a probe molecule attached to the surface via a crosslinker group is better able to hybridise to target DNA due to its greater mobility.

Characterization of a family of high-molecular-weight plasminogen activators secreted by a lung tumor cell line.

In an earlier publication (Harvey, et al. (1982) J. Biol. Chem., 257, 5645-5651) the discovery of a family of unusually large molecules with plasminogen activator activity in the conditioned medium of a human lung cancer cell line was reported. These molecules are related to urokinase (uPA) by functional and immunological criteria. We have now purified two representatives of this glycoprotein family of Mr 900,000 (PA900) and Mr 660,000 (PA660). While these could be fractionated into subspecies exhibiting size and charge differences, reduction yielded in all cases two predominant chains of 70 and 40 kDa, respectively. Since the amino acid composition of the subfractions was identical, we conclude that the heterogeneity is due to demonstrated differences in glycosylation. The amino acid composition of the unreduced species and of the major reduced chains differed from that of 55 kDa uPA. These enzymes are active toward the substrate, plasminogen, as well as toward the uPA-specific synthetic substrate, Spectrozyme UK, and these activities are inhibitable by diisopropylphosphorofluoridate (DFP). Treatment of PA660 with [3H]DFP resulted in the incorporation of 1.4 mol of DFP into 1 mol of enzyme, suggesting the presence of a single active site. The label was quantitatively recovered in a 21 kDa fragment in a reduction experiment. This fragment also demonstrated immunological reactivity with antiurokinase. It is postulated that PA660 is composed of five or six pairs of the 70 and 40 kDa chains, and of a single uPA-like entity. All of these chains are linked by disfulfide bonds. Whether larger portions of uPA are also present in this molecule, is not yet clear. By electron microscopy, PA900 shows a filamentous structure, while PA660 is predominantly globular. The occurrence of large uPA-like activators in extracts of human colon carcinomas that crossreact with monospecific antibody against uPA, is discussed.

Expression and capping of a proliferation-associated surface membrane p34 kDa antigen on different human hematopoietic cell lines.

A novel surface membrane nonglycosylated acidic polypeptide (34 kDa), encoded by a structural gene on chromosome 11, has been identified using murine monoclonal antibody (MoAb) 53.6 (IgG2a). MoAb 53.6, raised against uninduced cells of a human erythroleukemia line (HEL), recognizes a surface membrane antigen that is displayed on proliferating (cell cycle phase G1, S, and M + G2 phase) human leukocytes. The expression and redistribution (i.e., patching and capping) of the p34 kDa antigen on 27 different long-term human hematopoietic cell (HHC) lines was defined by fluorescence microscopy. These lines had been established from patients with leukemia or healthy donors and included phenotypically defined populations of T cells, B cells, and myelomonocytic cells. Almost all (greater than 95%) of the leukocytes of the 27 lines reacted strongly with MoAb 53.6. The majority of the leukocytes displayed p34 kDa antigen patching (26/27 lines; patched cells, 96-100%); moreover, 20 of 27 lines exhibited p34 kDa antigen capping (capped cells, 8-96%). Presentation of the p34 kDa antigen on surface membrane ultrastructures, imaged with immunogold using an indirect antibody labeling procedure, was illustrated by scanning electron microscopy, and endocytosis of the gold-tagged antigen-antibody complex was studied by transmission electron microscopy. The HHC lines are thought to represent immortalized populations of different human leukocyte subsets that are in different stages of maturation and/or differentiation; thus these lines should prove useful as models for further characterizing this unique p34 kDa proliferation-associated antigen and for defining the mechanisms and significance of surface membrane antigen redistribution and modulation that has been associated with leukocyte activation and propagation.

Effects of isolated right and left ventricular stretch on regional arteriolar resistance.

In order to evaluate right and left ventricular stretch receptors without concomitantly stimulating those of the contralateral ventricle, 12 dogs were placed on total cardiopulmonary bypass. Balloons connected to compliant reservoirs were introduced into the right and left ventricles. Changes in systemic, gracilis muscle, and paw perfusion pressure at a constant flow were used as indices of systemic, muscle, and cutaneous vascular resistance. To induce left ventricular stretch, the balloon in that chanber was rapidly inflated from a mean pressure of 1.33 kPa (10 mmHg) to a mean pressure of 7.32 kPa (55 mmHg) for 15s (6.00 kPa [45mmHg] increment). For right ventricular stretch, the pressure was increased from 0.67 to 4.00 kPa (5 to 30 mmHg) for 30 s (3.34 kPa [25 mmHg] increment). Both left and right ventricular stretch produced a significant fall in systemic (-4.92 kPa [-37 mmHg], -36%) and gracilis muscle (-5.59 kPa [-42 mmHg], -30%) perfusion pressure, with only minimal changes in cutaneous vascular resistance (-0.80 kPa [-6 mmHg], -4%). This reflex was found to be vagally mediated, to have a low threshold for stimulation (left ventricle, 0.67 kPa [5 mmHg] increment; right ventricle, 1.33 kPa [10 mmHg] increment), and to have a neurogenic sympathetic alpha-adrenergic efferent limb. The low threshold for stimulation suggests that these reflexes may play a physiological role with changes in body position and may be important in such pathological conditions as semilunar valvular stenosis and myocardial infarction.

Understanding Complete Pathologic Response in Oesophageal Cancer: Implications for Management and Survival.

Despite significant improvement over recent decades, oesophageal cancer survival rates remain poor. Neoadjuvant chemoradiotherapy followed by oesophageal resection is mainstay of therapy for resectable oesophageal tumours. Operative morbidity and mortality associated with oesophagectomy remain high and complications arise in up to 60% of patients. Management strategies have moved towards definitive chemoradiotherapy for a number of tumour sites (head and neck, cervical, and rectal) particularly for squamous pathology. We undertook to perform a review of the current status of morbidity and mortality associated with oesophagectomy, grading systems determining pathologic response, and data from clinical trials managing patients with definitive chemoradiotherapy to inform a discussion on the topic.