Clinical outcomes following surgical management of insertional Achilles tendinopathy using a double-row suture bridge technique with mean two-year follow-up.

BACKGROUND: The clinical outcomes following surgical management of insertional Achilles tendinopathy (IAT) vary depending on the surgical technique used to reattach the Achilles tendon following debridement. The aim of this study was to investigate the clinical outcomes of patients with IAT who underwent surgical management with a double-row suture bridge technique used to reattach the Achilles tendon. METHODS: A retrospective review of consecutive patients diagnosed with IAT, who underwent surgical management utilising a double-row suture bridge technique (Arthex Speedbridge), and a minimum of 3-month follow-up were included. The primary outcome was the Manchester-Oxford Foot Questionnaire (MOXFQ) Index score which is a patient reported outcome measure (PROM). Secondary outcomes included EuroQol EQ-5D-5L health-related quality of life PROM and complication rates. RESULTS: Between July 2013 and June 2020, 50 consecutive patients (23 male; 27 female) were included. The mean age (± standard deviation) was 52.3 ± 11.3 (range 29.0-84.3). Pre- and post-operative PROM data were available for all cases. The mean follow-up was 2.4 ± 1.9 years. The MOXFQ Index score improved from 48.5 to 12.4 (p < 0.01), EQ-5D-5L improved from 2.7 ± 0.46 to 1.2 ± 0.37 (p < 0.01), and EQ-VAS improved from 48.0 ± 18.4 to 84.1 ± 12.6 (p < 0.01). Four patients had complications which were of minimal clinical relevance and caused no deviation from routine recovery. There were no cases of tendon rupture. CONCLUSION: This study has demonstrated that surgical management of IAT is safe and effective with clinical improvement in both clinical and general health-related quality of life outcome PROMs. LEVEL OF EVIDENCE: IV.

The changing landscape of brachytherapy for cervical cancer: a Canadian practice survey.

BACKGROUND: We documented changes in practice from 2009 to 2012 for cervical cancer brachytherapy in Canada. METHODS: Centres with gynecologic brachytherapy services were sent an e-mail questionnaire querying their 2012 practice. Responses are reported and compared with practice patterns identified in a similar survey for 2009. RESULTS: The response rate was 77% (24 of 31 centres). Almost all use high-dose-rate brachytherapy (92%); low-dose-rate brachytherapy has been completely phased out. Most continue to move patients from the site of applicator insertion to the radiation treatment simulation suite (75%) or to a diagnostic imaging department (29%), or both. In 2012, the imaging modalities used for dose specification were computed tomography [ct (75%)], magnetic resonance imaging [mri (38%)], plain radiography (21%), and cone-beam ct (8%). The number of institutions using mri guidance has markedly increased during the period of interest (9 vs. 1). Most respondents (58% vs. 14%) prescribed using guidelines from the Groupe Européen de Curiethérapie and the European Society for Therapeutic Radiology and Oncology, but they also used point A as a reference. Commonly used high-dose radiation regimens included 30 Gy in 5 fractions and 24 Gy in 3 fractions. CONCLUSIONS: In Canada, image-guided brachytherapy for cervical cancer continues to evolve. Although ct-based imaging remains the most commonly used modality, many centres have adopted mri for at least 1 brachytherapy treatment. More centres are using fewer fractions and a slightly lower biologically effective dose, but are still achieving EQD2 (2-Gy equivalent) doses of 80-90 Gy in combination with external-beam radiation therapy.

Evaluation of transanal hemorrhoidal dearterialization: a single surgeon experience.

BACKGROUND: There is an increasing, though still limited, amount of evidence describing the use of the transanal hemorrhoidal dearterialization (THD) device for the treatment of hemorrhoidal disease. This study assesses postoperative outcomes from a single surgeon experience with the THD device. METHODS: From January 2009 to December 2011, 108 THD procedures were performed. With Doppler guidance, the THD device makes possible precise ligation of the branches of the superior hemorrhoidal artery. Patients were seen postoperatively at 3 weeks and 6 months. They underwent physical examination to determine whether there was recurrence of hemorrhoidal prolapse. They were asked to describe any bleeding, to rate pain using the visual analog scale, and to rate their level of satisfaction on a scale of 1-5 (with 5 = highly satisfied). A phone interview was used for follow-up at 1 year to determine the rate of recurrent prolapse. RESULTS: Of the 108 patients who underwent THD, two were lost to follow-up and excluded. All of the remaining 106 patients completed follow-up at 3 weeks and 6 months. At 3 weeks, 92% of patients had no pain and 88% were highly satisfied with the procedure at 3 weeks. This increased to 92% satisfaction at 1 year. Prolapse recurrence was 7.5% at 6 months and 10.3% at 1 year. Bleeding was the most common complication, but did not require re-intervention or transfusion. CONCLUSIONS: THD is a same-day procedure for the treatment of hemorrhoidal disease that is safe and effective, and offers the potential for immediate return to normal activity.

Afro Middle East Asian symposium on cancer cooperation.

This manuscript captures the discussion and recommendations that came out of a special Afro Asian symposium involving 13 countries. Unmet needs and cost-effective solutions with special emphasis on training form the backbone of practical next steps.

Sensitization to minor antigens is a significant barrier in bone marrow transplantation and is prevented by CD154:CD40 blockade.

Sensitization to major histocompatibility complex (MHC) alloantigens is critical in transplantation rejection. The mechanism of sensitization to minor histocompatibility antigens (Mi-HAg) has not been thoroughly explored. We used a mouse model of allosensitization to Mi-HAg to study the Mi-HAg sensitization barrier in bone marrow transplantation (BMT). AKR mice were sensitized with MHC congenic Mi-HAg disparate B10.BR skin grafts. Adaptive humoral (B-cells) and cellular (T cells) responses to Mi-HAg are elicited. In subsequent BMT, only 20% of sensitized mice engrafted, while 100% of unsensitized mice did. In vivo cytotoxicity assays showed that Mi-HAg sensitized AKR mice eliminated CFSE labeled donor splenocytes significantly more rapidly than naïve AKR mice but less rapidly than MHC-sensitized recipients. Sera from Mi-HAg sensitized mice also reacted with cells from other mouse strains, suggesting that Mi-HAg peptides were broadly shared between mouse strains. The production of anti-donor-Mi-HAg antibodies was totally prevented in mice treated with anti-CD154 during skin grafting, suggesting a critical role for the CD154:CD40 pathway in B-cell reactivity to Mi-HAg. Moreover, anti-CD154 treatment promoted BM engraftment to 100% in recipients previously sensitized to donor Mi-HAg. Taken together, Mi-HAg sensitization poses a significant barrier in BMT and can be overcome with CD154:CD40 costimulatory blockade.

An international comparison of governmental disclosure of hydrocarbon spills from offshore oil and gas installations.

The cumulative effect of accidental spills from oil and gas extraction in the marine environment can have significant impacts on marine wildlife. Oil and gas operators are typically required to report spill data as part of a regulatory process. We conducted a survey of the public disclosure of hydrocarbon spill data for four countries, Australia, Canada, United Kingdom and United States. There was significant variation in the spill data statistics that were publicly reported by the regulators. No country provided full disclosure of spill data or follow-up actions taken by the regulator on their website. The lack of disclosure of spill data is of concern because the scale of environmental effects is more difficult to assess, insufficient information is available to assess the accuracy of predictions made in the environmental assessment process, and without consistency of spill reporting there is no method to compare regional differences of spill rates.

Diversity of gammadelta T cells in patients with Behcet's disease is indicative of polyclonal activation.

OBJECTIVE: Behcet's disease (BD) is a multisystemic disease, with vasculitic lesions in the oral and genital mucosa, eyes, joints, skin and brain. We have previously found that gammadelta T cells are increased in peripheral blood of BD patients. The aim of this study was to investigate the extent of gammadelta T cells in oral biopsies from BD patients with special emphasis on the restriction of Vgamma and Vdelta usage. PATIENTS AND METHODS: Expression of Vgamma and Vdelta chains on peripheral blood gammadelta T cells from 31 BD patients and 19 healthy controls was analysed by flow cytometry and the expression of Vgamma and Vdelta chains in nine ulcerated and eight non-ulcerated oral mucosa from BD patients and non-ulcerated oral mucosa from three healthy controls was analysed by immunohistochemistry. RESULTS: Vgamma9 and Vdelta2 were the predominant chains expressed in peripheral blood of BD patients, although other Vgamma and Vdelta chains were also expressed. The presence of gammadelta T cells was only observed in the ulcerated oral mucosa but not in the non-ulcerated mucosa from the BD patients, and not in the non-ulcerated mucosa from the healthy controls. These gammadelta T cells showed no preferential expression of any of the Vgamma or Vdelta chains. CONCLUSION: These data suggest a polyclonal rather than oligoclonal activation of the gammadelta T cells. This may indicate that during repeated inflammation of the oral mucosa, the gammadelta T cells are responding to a wide variety of antigenic stimuli with consequent expansion of gammadelta T cells expressing various Vgamma and Vdelta chains and that different antigenic stimuli or responses may be responsible for the clinical heterogeneity of the disease.

Homing of mononuclear cells from iliac lymph nodes to the genital and rectal mucosa in non-human primates.

The route of immunization may affect the type of immunity that is induced. The objectives of this investigation were to establish in the non-human primate if the internal iliac lymph nodes (LN) function as an inductive site of immunity from which mononuclear cells home to the rectal and cervico-vaginal mucosa. Rhesus macaques were immunized with simian immunodeficiency virus (SIV) core antigen p27 in the proximity of the iliac lymph nodes, and compared with the intramuscular (i.m.) (deltoid or gluteal), and axillary LN routes of immunization. The macaques were then challenged rectally or vaginally by a particulate SIVp27 antigen which was applied to the mucosal surface. The tracking dye PKH26 was injected near the immunizing LN or i.m. site and a week later the mucosal and lymphoid tissues were examined at autopsy. Preferential homing of PKH26-labeled cells from the internal iliac LN to the rectal and vaginal mucosa was demonstrated by flow cytometry after targeted iliac LN (TILN) but not after intramuscular (deltoid) or axillary LN immunization. Homing of the subsets of cells revealed that labeled CD4, CD8 and B cells, as well as monocytes were found in the rectum, colon, vagina or cervix. The results of this investigation shows that the route of immunization may affect regional mucosal immunity. Furthermore, the internal iliac LN may function as an inductive immunological site from which CD4, CD8 and B cells may home preferentially to the rectal, cervical and vaginal mucosa, as well as to the related regional but not the unrelated distal LN.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone as a redox titrant.

An oxidimetric titrant, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in anhydrous acetic acid is used for the semimicro-determination of hydrazine hydrate, phenylhydrazine hydrochloride, isoniazid and iproniazid phosphate in pure forms as well as in some pharmaceutical preparations containing isoniazid and iproniazid phosphate. The end point was detected potentiometrically using a platinum-calomel combination electrode. The results obtained are compared statistically with those obtained by the official methods and they are in good agreement.

Investigation of the complement receptor 3 (CD11b/CD18) in human rectal epithelium.

Rectal and cervicovaginal mucosa are common routes of transmission of HIV, although the mechanism of transmission is unknown. We have investigated human rectal and cervicovaginal epithelia for the expression of complement receptors (CR) and cell adhesion molecules which may be involved in HIV and other infections. In rectal mucosa, CR3 was detected in the surface and crypt epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of 15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated in surface and crypt epithelial cells by in situ hybridization. Although CD11b was detected in the epithelial cells in three out of the 14 cervicovaginal specimens, we were unable to detect CD18. We suggest that expression of the CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding of HIV-antibody complexes in seminal fluid to epithelial cells. Alternatively, since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18, this may promote adhesion between epithelial cells and HIV-infected mononuclear cells in seminal fluid.

Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia.

Human immunodeficiency virus (HIV) is commonly transmitted, during homosexual and heterosexual intercourse, through the rectal and cervicovaginal mucosa, foreskin and urethral epithelia. However, there is uncertainty about HIV transmission through the oral mucosa by oral sex. We have carried out a comparative immunohistological investigation of primate oral, cervicovaginal, foreskin, urethral and rectal epithelia for potential HIV receptors. We investigated epithelial tissues for CD4 glycoprotein, which is the principal receptor for HIV, Fc receptors of IgG for binding HIV-IgG antibody complexes, and HLA class II, which might enable HIV-bound CD4+ cells to gain access to the epithelial cells. CD4 glycoprotein was not found in oral, foreskin, urethral, vaginal or rectal epithelial cells, although CD4+ mononuclear cells were present in the lamina propria of each epithelium. Fc gamma II and Fc gamma III receptors were found in urethral, endocervical and rectal epithelia, and Fc gamma III and Fc gamma I receptors in the foreskin. However, Fc gamma receptors were not found in oral epithelium (buccal, labial, lingual or palatal) and only Fc gamma III receptors were detected in the gingival epithelial cells. HLA class II antigen was also not detected in foreskin, oral or rectal epithelium, but it was expressed by endocervical cells from most human specimens and in male urethral epithelia of non-human male primates. Langerhans' cells were found in all epithelia except those of the urethra and rectum, and they can express CD4 glycoprotein, Fc gamma receptors and HLA class II antigen. The mean number of Langerhans' cells expressing CD4 in the upper third of oral epithelium was significantly lower compared with vaginal epithelium or foreskin. The HIV-binding V1 domain of CD4 was significantly decreased in Langerhans' cells present in oral compared with vaginal epithelium. The results suggest that the foreskin in uncircumcised men and the cervicovaginal epithelium in females might become infected via the CD4+ Langerhans' cells. However, urethral infection might be mediated by HIV-antibody complexes binding to urethral epithelial Fc gamma receptors. The paucity of Langerhans' cells expressing the V1 domain of CD4, the absence of Fc gamma receptors, and a lack of expression of HLA class II antigens in most oral epithelial cells, argue against transmission of HIV through the normal intact oral mucosa.

Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates.

A s.c. route of immunization was developed in non-human primates, which targets the genitourinary-rectal associated lymphoid tissue. A vaccine consisting of rSIV gag p27, expressed as hybrid Ty virus-like particles (p27: Ty-VLP) was administered in the proximity of the internal iliac lymph nodes. Secretory IgA and IgG Abs to the p27 Ag were elicited in the vaginal, male urethral, rectal and seminal fluids, urine and serum. Two or more immunodominant B cell epitopes were identified within peptides 51-90 and 121-170 of the sequence of p27, using serum or biliary IgA and IgG Abs. CD4+ T cell proliferative responses to p27 were elicited predominantly in the targeted internal iliac, as well as the inferior mesenteric lymph nodes and the spleen, but not in the unrelated lymph nodes. These cells were then studied for helper function in p27 specific B cell Ab synthesis. Specific IgA and IgG Abs were detected in the same lymphoid tissues as those that displayed proliferative responses. However, cross-over reconstitution experiments between splenic and iliac lymph node B and CD4+ T cells suggest that the iliac B cells are essential for specific IgA Ab synthesis, whereas splenic B cells preferentially synthesize IgG Ab. The targeted lymph node (TLN) route of immunization gave comparable B cell, proliferative T cell, and Th cell responses to the vaginal, male genitourinary, and rectal mucosal routes, which were augmented by oral immunization. However, the TLN route induced urinary and seminal fluid sIgA and IgG Abs in addition to genital and rectal Abs. Generating secretory IgA and IgG Abs at the mucosal surfaces, and T and B cell immunity in the regional draining lymph nodes, spleen and circulation by TLN immunization may prevent transmission of virus through the mucosa, dissemination of the virus, and the formation of a latent reservoir of infection.

Are pre-hospital deaths from accidental injury preventable?

OBJECTIVE: To determine what proportion of pre-hospital deaths from accidental injury--deaths at the scene of the accident and those that occur before the person has reached hospital--are preventable. DESIGN: Retrospective study of all deaths from accidental injury that occurred between 1 January 1987 and 31 December 1990 and were reported to the coroner. SETTING: North Staffordshire. MAIN OUTCOME MEASURES: Injury severity score, probability of survival (probit analysis), and airway obstruction. RESULTS: There were 152 pre-hospital deaths from accidental injury (110 males and 42 females). In the same period there were 257 deaths in hospital from accidental injury (136 males and 121 females). The average age at death was 41.9 years for those who died before reaching hospital, and their average injury severity score was 29.3. In contrast, those who died in hospital were older and equally likely to be males or females. Important neurological injury occurred in 113 pre-hospital deaths, and evidence of airway obstruction in 59. Eighty six pre-hospital deaths were due to road traffic accidents, and 37 of these were occupants in cars. On the basis of the injury severity score and age, death was found to have been inevitable or highly likely in 92 cases. In the remaining 60 cases death had not been inevitable and airway obstruction was present in up to 51 patients with injuries that they might have survived. CONCLUSION: Death was potentially preventable in at least 39% of those who died from accidental injury before they reached hospital. Training in first aid should be available more widely, and particularly to motorists as many pre-hospital deaths that could be prevented are due to road accidents.

Mucosal model of genital immunization in male rhesus macaques with a recombinant simian immunodeficiency virus p27 antigen.

Human immunodeficiency virus (HIV) can be transmitted through infected seminal fluid or vaginal or rectal secretions during heterosexual or homosexual intercourse. To prevent mucosal transmission and spread to the regional lymph nodes, an effective vaccine may need to stimulate immune responses at the genitourinary mucosa. In this study, we have developed a mucosal model of genital immunization in male rhesus macaques, by topical urethral immunization with recombinant simian immunodeficiency virus p27gag, expressed as a hybrid Ty virus-like particle (Ty-VLP) and covalently linked to cholera toxin B subunit. This treatment was augmented by oral immunization with the same vaccine but with added killed cholera vibrios. Polymeric secretory immunoglobulin A (sIgA) and IgG antibodies to p27 were induced in urethral secretions, urine, and seminal fluid. This raises the possibility that the antibodies may function as a primary mucosal defense barrier against SIV (HIV) infection. The regional lymph nodes which constitute the genital-associated lymphoid tissue contained p27-specific CD4+ proliferative and helper T cells for antibody synthesis by B cells, which may function as a secondary immune barrier to infection. Blood and splenic lymphocytes also showed p27-sensitized CD4+ T cells and B cells in addition to serum IgG and IgA p27-specific antibodies; this constitutes a third level of immunity against dissemination of the virus. A comparison of genito-oral with recto-oral and intramuscular routes of immunization suggests that only genito-oral immunization elicits specific sIgA and IgG antibodies in the urine, urethra, and seminal fluid. Both genito-oral and recto-oral immunizations induced T-cell and B-cell immune responses in regional lymph nodes, with preferential IgA antibody synthesis. The mucosal route of immunization may prevent not only virus transmission through the genital mucosa but also dissemination and latency of the virus in the draining lymph nodes.

T- and B-cell functions and epitope expression in nonhuman primates immunized with simian immunodeficiency virus antigen by the rectal route.

Transmission of human immunodeficiency virus (HIV) in North America and Europe occurs most commonly through the rectal mucosa during homosexual intercourse. The simian immunodeficiency virus (SIV) macaque model has been used to investigate rectal immunization. The vaccine used was a recombinant SIV gag p27 expressed as hybrid Ty virus-like particles (Ty-VLP). Sequential ororectal (OR) mucosal immunization was compared with i.m. immunization. Whereas both routes of immunization induced serum IgA and IgG p27 antibodies, only OR immunization induced rectal secretory IgA antibodies. Specific CD4+ T-cell proliferative responses to stimulation with p27 were found after i.m. immunization only in the blood and spleen, but after OR immunization they were found in the internal iliac and inferior mesenteric lymph nodes in addition to the blood and spleen. T-cell epitope mapping of the proliferative responses of short-term cell lines (STCLs) grown from peripheral blood or lymphoid cells revealed a major epitope within the polypeptide 121-150 after either route of immunization. Two minor T-cell epitopes were found within peptide 41-80 in STCLs from splenic and circulating cells. B-cell epitope mapping of serum or biliary IgA and IgG antibodies revealed two overlapping or adjacent immunodominant epitopes to the T-cell epitopes within the polypeptides 121-170 and 51-90. The results suggest that rectal augmented by oral immunization with a recombinant particulate antigen in nonhuman primates elicits secretory IgA and to a lesser extent IgG responses in the draining lymph nodes and the rectal mucosa, whereas systemic immunization targets predominantly splenic and circulating T- and B-cell responses. These findings may have important implications in the strategy of designing vaccines in prevention of homosexual transmission of HIV infection.

Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and Langerhans cells in human cervico-vaginal epithelium.

The mechanism of transmission of HIV from the male to the female genital tract or in the reverse order is not clear. CD4 glycoprotein is the receptor for HIV and Langerhans cells and the related dendritic cells could play a role in the initial transmission of HIV. Fc receptors (FcR) for IgG might be involved in antibody-mediated binding of HIV. We carried out an immunohistological study of normal human cervical and vaginal epithelia for the presence of CD4 glycoprotein, Langerhans cells and FcR to IgG. CD4+ glycoprotein was not found in the vaginal or cervical epithelium, with the exception of a few endocervical epithelial cells. A small number of CD4+ mononuclear cells were found in the endocervical epithelium of a third of the specimens but a large number of CD4+ cells was found in the submucosa of most of the cervical and vaginal specimens. Langerhans cells expressing CD4, HLA class II, Fc gamma R2 and Fc gamma R3 were detected in most vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervical tissues. Fc gamma R3 was detected in about two-thirds of the columnar endocervical epithelium and the transformation zone. A smaller number of specimens expressed Fc gamma R2 in these epithelia, but Fc gamma R1 was not detected. We then demonstrated mRNA for Fc gamma R3 in the columnar endocervical epithelial cells and transformation zone by in situ hybridization, using a CD16-RNA probe. Fc gamma R3 and Fc gamma R2 gene transcripts were also found in fetal cervical tissue by applying the polymerase chain reaction to amplify portions of the Fc gamma R3 and Fc gamma R2 coding sequences in cDNA prepared from fetal RNA. HLA-DR was found in the endocervical cells, transformation zone and in Langerhans cells of all specimens. The presence of Langerhans cells, Fc gamma receptors and HLA class II antigen offers three potential mechanisms for cervico-vaginal HIV transmission: (i) direct HIV infection of Langerhans cells, (ii) binding of HIV antibody complexes to cervical epithelial Fc gamma receptors and (iii) binding of HIV infected CD4+ cells to cervical HLA class II antigen which may infect these or the adjacent CD4+ cells.

Induction of mucosal and systemic immunity to a recombinant simian immunodeficiency viral protein.

Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4+ T cell proliferative and helper functions in the circulating blood.