Fighting cervical cancer in Africa: a cross-sectional study on prevalence and risk factors for precancerous lesions in rural Uganda.

OBJECTIVE: To identify risk factors for precancerous cervical lesions and factors associated with treatment delay among women in the rural Busoga Region, Uganda. STUDY DESIGN: A retrospective cross-sectional study from a regional cervical cancer screening program and from cervical cancer patients enrolled in a region-wide palliative care program. METHODS: Logistic regression analysis was conducted to assess risk factors for screening positive for precancerous lesions. In a separate analysis, factors associated with treatment delay were assessed among women enrolled in the palliative care program. RESULTS: Three thousand nine hundred forty-six women were included from the screening program and 334 from the palliative care program. In total, 7.6% of screening participants had precancerous lesions. Within Busoga Region, the highest positivity rate was found in Bugweri and Namayingo Districts. Abnormal vaginal bleeding (adjusted odds ratio [aOR] 1.60; 95% confidence interval [CI] 1.15-2.21; p = 0.005) and older age at first menstrual period (aOR 1.08; 95% CI 1.01-1.16; p = 0.03) were associated with having a precancerous lesion. Among palliative care patients, a history of previous contact with the health care system was associated with a delay in enrolment (≥12 months from first symptom presentation until commencement in palliative care; aOR 5.23; 95% CI 1.16-36.54; p = 0.047). CONCLUSIONS: The results underline an unmet need for broad-scale cervical cancer screening focusing on all women in the reproductive age. Abnormal bleeding was the only substantial risk factor for precancerous lesions, indicating that specific algorithms to identify high-risk populations may not be applicable in this population. Increased awareness, resources, and funding are still necessary to achieve global cervical cancer elimination.

Can a humid storage environment of surgical instruments before reprocessing increase patient safety and durability of instruments?

BACKGROUND: National and international guidelines recommend reprocessing of medical instruments to commence as soon as possible post-surgery; furthermore, they recommend that transport and storage of surgical instruments postoperatively occurs in a moist, humid atmosphere. The concern is that a dry storage environment results in deterioration of instruments. AIM: To evaluate whether residual protein or corrosion is associated with storage environment (dry or humid), holding time or number of treatment cycles. METHODS: The range of protein residue and corrosion were tested on surgical instruments contaminated with human blood amended Enterococcus faecalis ATCC 29212. Subsequently instruments were stored for 6, 12 and 24 h in dry or humid conditions. After one, 25 and 50 reprocessing cycles, instruments were examined for protein residues using the o-phthaldialdehyde (OPA) method or corrosion using stereomicroscopy, scanning electron microscopy and energy dispersive spectroscopy. FINDINGS: Protein residue found on instruments was 21.5-54.0 µg and corrosion corresponded to 0-5% of the inspected area. No associations between storage environment and protein residue (adjusted mean difference = 0.48, 95% confidence interval: -0.42, 1.37, P=0.30) or corrosion (P=0.20) were identified. Higher numbers of treatment cycles showed higher amounts of corrosion (mean: 1cycle = 0.06%, 25cycles = 0.52% and 50cycles = 1.45%). In contrast, higher numbers of treatment cycles showed lower amounts of protein residue (P<0.001). We found both lower protein residue concentration and lower corrosion rating at 12 h compared with 6 and 24 h holding time. CONCLUSION: Cleanliness and durability of instruments before reprocessing seems not to be affected by storage environment or holding time but instead by number of treatment cycles.

Biofiltration of diluted landfill gas in an active loaded open-bed compost filter.

Microbial oxidation in a biofilter is a treatment solution for diluted landfill gas (LFG), for instance at old landfills, where LFG recovery is no longer feasible, or from remediation systems designed to cut off laterally migrating LFG. In this study, an actively loaded open-bed compost filter, designed for the treatment of diluted LFG, was tested at an old landfill in Denmark. An 18 m3 biofilter was constructed in a 30 m3 container loaded with LFG mixed with air, in order to obtain diluted LFG. The inlet concentration of methane (CH4) fluctuated between 4.4 and 9.2 vol% during the five tested flow campaigns, resulting in CH4 loads of 106-794 g CH4 m-2 d-1. The maximum identified CH4 oxidation rate was 460 g m-2 d-1, with an overall CH4 oxidation efficiency of 58%. Due to preferential flows, especially along the edges of the filter at the transition points between the compost and the container wall, an overall CH4 oxidation efficiency of 100% was never achieved. However, pore gas profiles in selected areas in the filter material showed oxidation efficiencies close to 100%. The results were supported by tracer gas tests showing average oxidation efficiency in the nine measuring points of 89% at a CH4 load of 487 ± 64 g CH4 m-2 d-1.

Challenging the six-hour recommendation for reprocessing sterilizable medical equipment.

BACKGROUND: At present, reprocessing of sterilizable medical equipment is recommended to be initiated within 6 h after completion of surgery, to ensure that the quality of the instruments does not deteriorate. A literature search showed a lack of evidence for consequences that may occur if medical personnel deviate from the standard 6 h sterilization protocol. AIM: To evaluate the 6 h recommendation for reprocessing sterilizable medical equipment by determining whether residual protein increased proportional to holding time before reprocessing was initiated, and likewise whether an increase in corrosion was present on surgical scissors proportional to holding time. METHODS: Residual protein was identified on surgical instruments contaminated with human blood after different holding times and before washes using the o-phthaldialdehyde (OPA) method. Corrosion was identified on surgical scissors contaminated with human blood after different holding times and after reprocessing using light stereomicroscopy and scanning electron microscopy. FINDINGS: Protein residues ranged between 14.0 and 51.9 µg and thus below the accepted threshold of 100 µg per instrument surface. Corrosion corresponding to 0.05% of the surface was identified on 22 of 30 scissors. Pitting corrosion was seen on four of 30 scissors. CONCLUSION: No association was identified between residual protein and holding time, nor between incidence of corrosion and holding time. The study thereby challenges the relevance of upholding the recommendation of a maximum wait of 6 h prior to reprocessing. The findings will potentially have an impact on the organization of reprocessing of surgical instruments in Denmark and internationally.

Short implants (≤8mm) compared to standard length implants (>8mm) in conjunction with maxillary sinus floor augmentation: a systematic review and meta-analysis.

The objective was to test the hypothesis of no difference in the treatment outcome after the installation of short implants (≤8mm) in the posterior part of the maxilla compared to standard length implants (>8mm) in conjunction with maxillary sinus floor augmentation (MSFA) using the lateral window technique, after an observation period of ≥3years. A search of the MEDLINE, Embase, and Cochrane Library databases, in combination with a hand-search of relevant journals, was conducted. The search yielded 1102 titles. Finally, three studies that fulfilled the inclusion criteria were included. All were considered to have a low risk of bias. Meta-analyses revealed no significant differences in implant survival or peri-implant marginal bone loss between the two treatment modalities. However, the use of standard length implants in conjunction with MSFA was characterized by a tendency towards more peri-implant marginal bone loss. There was no statistically significant difference between the two treatment modalities with regard to overall patient satisfaction. Short implants seem to be a suitable alternative to standard length implants in conjunction with MSFA. However, further randomized controlled trials with larger patient samples and an observation period of more than 3years are needed before one treatment modality might be considered superior to the other.

A systematic review and meta-analysis of long-term studies (five or more years) assessing maxillary sinus floor augmentation.

The objective was to test the hypothesis of no difference in long-term (≥5 years) implant treatment outcomes after maxillary sinus floor augmentation (MSFA) with autogenous bone graft compared to a mixture of autogenous bone graft and bone substitutes or bone substitutes alone. A MEDLINE (PubMed), Embase, and Cochrane Library search in combination with a hand-search of relevant journals was conducted. Human studies published in English between January 1, 1990 and October 1, 2016 were included. Nine studies fulfilled the inclusion criteria. The survival of suprastructures has never been compared within the same study. The 5-year implant survival after MSFA with autogenous bone graft was 97%, compared to 95% for Bio-Oss; the reduction in vertical height of the augmented sinus was equivalent with the two treatment modalities. Non-comparative studies demonstrated high survival rates for suprastructures and implants regardless of the grafting material used. Meta-analysis revealed an overall estimated patient-based implant survival of 95% (confidence interval 0.92-0.96). High implant stability quotient values, high patient satisfaction, and limited peri-implant marginal bone loss were revealed in non-comparative studies. No long-term randomized controlled trial comparing the different treatment modalities was identified. Hence, the conclusions drawn from the results of this systematic review should be interpreted with caution.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.

AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

Galectin-3 is Persistently Increased in Early Rheumatoid Arthritis (RA) and Associates with Anti-CCP Seropositivity and MRI Bone Lesions, While Early Fibrosis Markers Correlate with Disease Activity.

Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 µg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 µg/l [2.6;4.9], P = 0.05) and controls (3.8 µg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti-CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes.

Pain and pain mechanisms in patients with inflammatory arthritis: A Danish nationwide cross-sectional DANBIO registry survey.

BACKGROUND: Central pain mechanisms may be prominent in subsets of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features, which may act as a proxy for centrally mediated pain. The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months. Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ-score >18 indicated neuropathic pain features, 13-18 unclear pain mechanism and <13 non-neuropathic pain. RESULTS: Pain data (visual analogue scale, VAS) was available for 15,978 patients. 7,054 patients completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/ >18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ > 18 significantly higher scores were found for all patient reported outcomes and disease activity scores. No clinical difference in CRP or swollen joint count was found. Logistic regression showed increased odds for having VAS pain ≥39 mm (the median) for a PDQ-score >18 compared to <13 (OR = 10.4; 95%CI 8.6-12.5). CONCLUSIONS: More than 50% of the Danish arthritis patients reported clinically significant pain. More than 20% of the PDQ-completers had indication of neuropathic pain features, which was related to a high pain-level. PDQ-score was associated with DAS28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment.

Injectable silver nanosensors: in vivo dosimetry for external beam radiotherapy using positron emission tomography.

Development of safe and efficient radiotherapy routines requires quantification of the delivered absorbed dose to the cancer tissue in individual patients. In vivo dosimetry can provide accurate information about the absorbed dose delivered during treatment. In the current study, a novel silver-nanosensor formulation based on poly(vinylpyrrolidinone)-coated silver nanoparticles formulated in a gelation matrix composed of sucrose acetate isobutyrate has been developed for use as an in vivo dosimeter for external beam radiotherapy. In situ photonuclear reactions trigger the formation of radioactive (106)Ag, which enables post treatment verification of the delivered dose using positron emission tomography imaging. The silver-nanosensor was investigated in a tissue equivalent thorax phantom using clinical settings and workflow for both standard fractionated radiotherapy (2 Gy) and stereotactic radiotherapy (10- and 22 Gy) in a high-energy beam setting (18 MV). The developed silver-nanosensor provided high radiopacity on the planning CT-scans sufficient for patient positioning in image-guided radiotherapy and provided dosimetric information about the absorbed dose with a 10% and 8% standard deviation for the stereotactic regimens, 10 and 22 Gy, respectively.

Multidrug-resistant tuberculosis in New South Wales, Australia, 1999-2010: a case series report.

SETTING: The emergence of multidrug-resistant tuberculosis (MDR-TB) threatens the ongoing control of tuberculosis (TB). The Australian state of New South Wales (NSW) has low TB and MDR-TB incidence. OBJECTIVE: To examine the epidemiology and the clinical and public health management of MDR-TB in NSW. DESIGN: A retrospective case-series analysis of MDR-TB diagnosed in NSW between 1999 and 2010 was undertaken. A standardised questionnaire was used to collect information from the public health surveillance system, medical records and the State Mycobacterium Reference Laboratory about clinical features, drug susceptibility, treatment regimens, hospitalisation, risk factors for tuberculous infection, contact tracing and patient outcomes. RESULTS: Fifty-five cases of culture-confirmed MDR-TB, including two cases of extensively drug-resistant TB, were diagnosed. All cases were reviewed by an expert management panel. Fifty cases (91%) were foreign-born, and 50 cases (91%) had fully supervised treatment. Of the 55 cases, 46 (84%) successfully completed treatment, 3 (5%) died of TB and 3 (5%) required surgery. No MDR-TB cases were reported among contacts. CONCLUSION: Using a multidisciplinary, expert guided, case-management approach, the NSW TB Control Program achieved excellent MDR-TB outcomes. The impact of global increases in MDR-TB requires sustained commitment to TB in all settings.

Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis.

OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.

Depletion of regulatory T cells in a hapten-induced inflammation model results in prolonged and increased inflammation driven by T cells.

Regulatory T cells (Tregs ) are known to play an immunosuppressive role in the response of contact hypersensitivity (CHS), but neither the dynamics of Tregs during the CHS response nor the exaggerated inflammatory response after depletion of Tregs has been characterized in detail. In this study we show that the number of Tregs in the challenged tissue peak at the same time as the ear-swelling reaches its maximum on day 1 after challenge, whereas the number of Tregs in the draining lymph nodes peaks at day 2. As expected, depletion of Tregs by injection of a monoclonal antibody to CD25 prior to sensitization led to a prolonged and sustained inflammatory response which was dependent upon CD8 T cells, and co-stimulatory blockade with cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) suppressed the exaggerated inflammation. In contrast, blockade of the interleukin (IL)-10-receptor (IL-10R) did not further increase the exaggerated inflammatory response in the Treg -depleted mice. In the absence of Tregs , the response changed from a mainly acute reaction with heavy infiltration of neutrophils to a sustained response with more chronic characteristics (fewer neutrophils and dominated by macrophages). Furthermore, depletion of Tregs enhanced the release of cytokines and chemokines locally in the inflamed ear and augmented serum levels of the systemic inflammatory mediators serum amyloid (SAP) and haptoglobin early in the response.

Transforaminal lumbar interbody fusion vs. posterolateral instrumented fusion: cost-utility evaluation along side an RCT with a 2-year follow-up.

PURPOSE: Long-lasting low back pain is an increasing problem, and for some patients surgery is the final option for improvement. Several techniques for spinal fusion are available and the optimal technique remains uncertain. The objective of this study was to assess the cost-effectiveness and cost-utility of transforaminal lumbar interbody fusion (TLIF) compared to posterolateral instrumented fusion (PLF) from the societal perspective. METHODS: 100 Patients were randomized to TLIF or PLF (51/49) and followed for 2 years. Cost data were acquired from national registers, and outcomes were measured using the Oswestry Disability Index and SF-6D questionnaires. Conventional cost-effectiveness methodology was employed to estimate net benefit and to illustrate cost-effectiveness acceptability curves. The statistical analysis was based on means and bootstrapped confidence intervals. RESULTS: Results showed no statistically significant difference in either cost or effects although a tendency for the TLIF regimen being more costly on bed days (2,554) and production loss (1,915) was observed. The probability that TLIF would be cost-effective did not exceed 30 % for any threshold of willingness to pay per quality-adjusted life year. Sensitivity analysis was conducted and supported the statistical model for handling of missing data. CONCLUSION: TLIF does not seem to be a relevant alternative to PLF from a socioeconomic, societal point of view.

Progesterone exposure of seasonally anoestrous ewes alters the expression of angiogenic growth factors in preovulatory follicles.

Small-dose, multiple injections of GnRH given to seasonally anoestrous ewes induce final stages of the preovulatory follicle development, but result in an high incidence of defective CL unless animals are primed with progesterone, which completely eliminates luteal dysfunction. Progesterone priming upregulates luteal vascularization; however, its effect on follicular angiogenesis is poorly understood. This study tested the hypothesis that progesterone priming of seasonally anoestrous ewes treated with dose multiple injections of GnRH eliminates defective luteal function by altering the expression of vascular endothelial growth factor (VEGF), VEGF receptor-2, angiopoietin (ANG)-1, ANG-2, and TIE-2 during early and late preovulatory follicle development. Ten seasonally anoestrous ewes were given 20 mg of progesterone im 3 days before the start of GnRH treatment; 10 other animals served as controls. Intravenous injections of 500 ng GnRH were given to all animals every 2 hours for 28 hours, followed at 30 hours with a 300-µg GnRH bolus injection to synchronize the preovulatory LH surge. Ovaries were collected at 24 and 46 hours after the start of GnRH treatment. Small (2-2.5 mm) and large (>2.5 mm) follicles were analyzed for protein and mRNA expression of the angiogenic factors using immunohistochemistry and in situ hybridization assays. Progesterone priming did not have an influence on angiogenic factor levels in small follicles. However, progesterone-primed animals showed significantly (P ≤ 0.05) higher levels of VEGF, VEGFR-2, ANG-1, and ANG-2 in large follicles compared with nonprimed ones. These data suggest that progesterone priming alters the expression of angiogenic factors in large preovulatory follicles, ensuring adequate luteal development and function.

Ten-year retrospective study of head and neck carcinoma in situ: incidence, treatment, and clinical outcome.

OBJECTIVES: To examine the management and clinical outcome for patients with primary head and neck carcinoma in situ (CIS) and to estimate the incidence in the referral population. STUDY DESIGN: A retrospective study from 2000-2009 of patients with head and neck CIS referred for treatment at Rigshospitalet. The referral area was East Denmark and Greenland with a population of 2.4 million. RESULTS: Fifty-five patients with primary CIS were identified: 21 oral cavity, 7 pharynx, 25 larynx, 2 nasal cavity/paranasal sinuses. The median annual incidence was 0.24/100,000. Eleven patients (20%) had T-site recurrence. The 5-year disease-specific survival rate and 5-year recurrence-free survival rate were 98% and 74% respectively. CONCLUSIONS: The annual incidence of primary head and neck CIS was low and in accordance with previous findings reported in the literature. We recommend that CIS lesions should be treated on T-site and surveilled as T1/T2 head and neck carcinomas.

Waiting times for diagnosis and treatment of head and neck cancer in Denmark in 2010 compared to 1992 and 2002.

BACKGROUND AND AIM: Significant tumour progression was observed during waiting time for treatment of head and neck cancer. To reduce waiting times, a Danish national policy of fast track accelerated clinical pathways was introduced in 2007. This study describes changes in waiting time and the potential influence of fast track by comparing waiting times in 2010 to 2002 and 1992. METHODS: Charts of all new patients diagnosed with squamous cell carcinoma of the oral cavity, pharynx and larynx at the five Danish head and neck oncology centres from January to April 2010 (n=253) were reviewed and compared to similar data from 2002 (n=211) and 1992 (n=168). RESULTS: The median time to diagnosis was 13 days (2010) versus 17 days (2002; p<0.001) and 20 days (1992; p<0.001). Median days from diagnosis to treatment start were 25 (2010) versus 47 (2002; p<0.001) and 31 (1992; p<0.001). Total pre-treatment time was median 41 days in 2010 versus 69 days (2002) (p<0.001) and 50 days (1992; p<0.001). Significantly more diagnostic imaging was done in 2010 compared to 2002 and 1992. When compared to current fast track standards the adherence to diagnosis improved slightly from 47% (1992) to 51% (2002) and 64% (2010); waiting time for radiotherapy was within standards for 7%, 1% and 22% of cases, respectively; waiting time for surgery was within standards for 17%, 22% and 48%, respectively. CONCLUSION: The study showed a significant reduction in delay of diagnosis and treatment of head and neck cancer in 2010, but still less than half of all patients start treatment within the current standards.

Hormonal regulation of female reproduction.

Reproduction is an event that requires the coordination of peripheral organs with the nervous system to ensure that the internal and external environments are optimal for successful procreation of the species. This is accomplished by the hypothalamic-pituitary-gonadal axis that coordinates reproductive behavior with ovulation. The primary signal from the central nervous system is gonadotropin-releasing hormone (GnRH), which modulates the activity of anterior pituitary gonadotropes regulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) release. As ovarian follicles develop they release estradiol, which negatively regulates further release of GnRH and FSH. As estradiol concentrations peak they trigger the surge release of GnRH, which leads to LH release inducing ovulation. Release of GnRH within the central nervous system helps modulate reproductive behaviors providing a node at which control of reproduction is regulated. To address these issues, this review focuses on several critical questions. How is the HPG axis regulated in species with different reproductive strategies? What internal and external conditions modulate the synthesis and release of GnRH? How does GnRH modulate reproductive behavior within the hypothalamus? How does disease shift the activity of the HPG axis?

Progesterone exposure of the preovulatory follicle in the seasonally anestrous ewe alters the expression of angiogenic growth factors in the early corpus luteum.

Gonadotrophin releasing hormone (GnRH)-induced ovulation in seasonally anestrous ewes is associated with a high incidence of defective corpora lutea (CL), which can be completely eliminated by priming ewes with progesterone before GnRH treatment, but the physiological basis of this has remained elusive. This study tested the hypothesis that progesterone priming eliminates defective luteal function by altering the expression of Vascular Endothelial Growth Factor (VEGF), its receptor VEGFR-2, and angiopoietin (ANG)-1, ANG-2 and their receptor TIE-2 in the early CL. Fifteen seasonally anestrous ewes were treated by i.m. injection with 20 mg of progesterone 3 days before the start of GnRH treatment, while another 15 animals served as controls. Intravenous injections of 500 ng GnRH were given to all the ewes every 2 h for 28 h, followed by a 300 µg GnRH bolus injection to synchronize the preovulatory luteinizing hormone (LH) surge. Corpora lutea were collected 1, 2 and 4 days after ovulation and analyzed for protein and mRNA expression of VEGF, VEGFR-2, ANG-1, ANG-2 and Tie-2 using Western Immunoblotting and in situ hybridization. VEGF, VEGFR-2 and ANG-1 expression was significantly higher (P ≤ 0.05) in the CL of progesterone-primed animals compared to non-primed ones. However, no differences were observed in the ANG-2 or Tie-2 expression levels between the two treatment groups. These data suggest that progesterone priming of the preovulatory follicle alters the expression of some angiogenic growth factors in the early CL, leading to greater vascular stability and thereby normal luteal function.

Branchial ionocyte organization and ion-transport protein expression in juvenile alewives acclimated to freshwater or seawater.

The alewife (Alosa pseudoharengus) is a clupeid that undergoes larval and juvenile development in freshwater preceding marine habitation. The purpose of this study was to investigate osmoregulatory mechanisms in alewives that permit homeostasis in different salinities. To this end, we measured physiological, branchial biochemical and cellular responses in juvenile alewives acclimated to freshwater (0.5 p.p.t.) or seawater (35.0 p.p.t.). Plasma chloride concentration was higher in seawater-acclimated than freshwater-acclimated individuals (141 mmol l(-1) vs 134 mmol l(-1)), but the hematocrit remained unchanged. In seawater-acclimated individuals, branchial Na(+)/K(+)-ATPase (NKA) activity was higher by 75%. Western blot analysis indicated that the abundance of the NKA α-subunit and a Na(+)/K(+)/2Cl(-) cotransporter (NKCC1) were greater in seawater-acclimated individuals by 40% and 200%, respectively. NKA and NKCC1 were localized on the basolateral surface and tubular network of ionocytes in both acclimation groups. Immunohistochemical labeling for the cystic fibrosis transmembrane conductance regulator (CFTR) was restricted to the apical crypt of ionocytes in seawater-acclimated individuals, whereas sodium/hydrogen exchanger 3 (NHE3) labeling was present on the apical surface of ionocytes in both acclimation groups. Ionocytes were concentrated on the trailing edge of the gill filament, evenly distributed along the proximal 75% of the filamental axis and reduced distally. Ionocyte size and number on the gill filament were not affected by salinity; however, the number of lamellar ionocytes was significantly lower in seawater-acclimated fish. Confocal z-series reconstructions revealed that mature ionocytes in seawater-acclimated alewives occurred in multicellular complexes. These complexes might reduce paracellular Na(+) resistance, hence facilitating Na(+) extrusion in hypo-osmoregulating juvenile alewives after seaward migration.