Living on the edge: latitudinal variations in the reproductive biology of two coastal species of sharks.

Differences in the reproductive biology of both the Australian weasel shark Hemigaleus australiensis and the Australian sharpnose shark Rhizoprionodon taylori were apparent between individuals from the southern-most extent of their range in eastern Australia (Moreton Bay) and those from northern Australia. For H. australiensis from Moreton Bay the total length (LT ) at which 50% of individuals were mature (LT50 ) was 759 mm for females and 756 mm for males, values that were respectively 17-26% larger than reported for the species in northern Australia. The relatively low percentage (63%) of pregnant mature females and presence of small, similar-sized, embryos in utero in both May and November suggested a semi-synchronous, annual reproductive cycle in Moreton Bay, whereas a synchronous, biannual reproductive cycle occurred in northern Australia. It is likely that H. australiensis has a resting phase between gestation cycles at the southern-most extent of its range. For R. taylori from Moreton Bay the LT50 s were 588 and 579 mm for females and males, respectively, values 2-3% larger than for individuals from the mid-Queensland coast and 31-35% larger than for individuals from northern Australia. The length at which 50% of the females were maternal (611 mm LT ) in Moreton Bay was greater than the LT50 , indicating that not all sharks mate immediately after maturing. Rhizoprionodon taylori in the south had an annual reproductive cycle incorporating a 7-8 month embryonic diapause, with pups probably born in February. A mean fecundity of 7·5 was almost double that reported from northern Australia. Regional variations in the reproductive characteristics of H. australiensis and R. taylori may influence their resilience to fishing and other anthropogenic pressures. The substantial differences reported here highlight the importance of region-specific life-history parameters to successful management and conservation.

Worldwide incidence of cervical lesions: a systematic review.

We conducted a systematic review summarizing data on incidence of high- and low-grade lesions in women with normal baseline cervical cytology, stratified by age (<30 and ⩾30 years), and baseline human papillomavirus (HPV) infection. Incidence of high- and low-grade lesions in women aged ⩾30 years with a baseline HPV infection increased over follow-up time (5-127 months), although incidence generally remained <10%. Without baseline HPV infection, incidence of high-grade lesions remained low over follow-up time (<5% over 5-122 months). Incidence of high-grade lesions in women aged ⩾30 years with baseline HPV infection appeared similar to that in women aged <30 years. In some women aged <30 years, high-grade lesions can develop relatively shortly after initial HPV infection. We observed an increase in low-grade lesions over time in women aged ⩾30 years with baseline HPV infection, potentially indicative of an HPV infection that is potentially progressing to higher grade lesions.

Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing.

The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg/kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high-performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0-24 : minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 µg/mL, which is lower than the recommended target of 20-25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13-30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.

Size, sex and seasonal patterns in the assemblage of Carcharhiniformes in a sub-tropical bay.

Size, sex and seasonal patterns among Carcharhiniformes were examined in shallow regions of Moreton Bay, Queensland, Australia. A total of 1259 sharks were caught, comprising 13 species. The Australian sharpnose shark Rhizoprionodon taylori and the blacktip complex Carcharhinus limbatus-Carcharhinus tilstoni comprised 55% of all shark individuals. Neonates were observed for five species including the dusky shark Carcharhinus obscurus, which contrary to previous reports was relatively abundant in shallow, predominantly estuarine waters. Three contrasting patterns of occurrence were observed: smaller species were abundant and present throughout much of their ontogeny, larger species were mainly caught as neonates or juveniles and vagrant species were only caught during the warmer months. The shark assemblage differed significantly among seasons. While many species were observed during the warmer months, species diversity was lower in winter when C. obscurus comprised 43% of the catch. Overall, the results indicated that spatial and temporal distribution patterns were not synchronous for all species. The capture of small numbers of neonate C. obscurus in late autumn and winter demonstrates that parturition among Carcharhiniformes is not confined to spring and summer in sub-tropical waters.

The pericranial flap for inner lining of full-thickness nasal defects: a retrospective cohort study.

BACKGROUND: Effective nasal reconstruction requires skin and soft tissue cover, cartilage or bone structure, and mucosal lining. Ideal lining is thin, pliable and vascularised, making reconstruction challenging. This paper presents the first case series with long-term outcomes of pericranial flaps used as inner lining for nasal reconstruction. METHODS: Patients undergoing paramedial forehead flaps from 2007 to 2019 were identified using second-stage nasal reconstruction billing codes. Patients with pericranial flaps for lining, for whom there were data on resulting outcomes and complications, were identified. RESULTS: Sixty-six patients underwent second-stage nasal reconstruction. Eighteen patients had paramedian forehead and pericranial flaps for inner lining reconstruction. The flap lining had no immediate post-operative complications. Three patients suffered partial to major reconstructive failure post radiotherapy. Other complications included nasal stenosis and orocutaneous fistula. CONCLUSION: Combined with paramedian forehead flaps, the pericranial flap is reliable as inner lining for nasal reconstruction. It is easily accessible and useful in resections with limited mucosal options.

Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: The complement activation product 5a (C5a) is a potent mediator of the innate immune response to infection, and may thus also importantly determine the development of periodontitis. The present study was designed to explore the effect of several novel, potent and orally active C5a receptor (CD88) antagonists (C5aRAs) on the development of ligature-induced periodontitis in an animal model. MATERIAL AND METHODS: Three different cyclic peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of experimental periodontitis, rats either received one of the C5aRas (1-2 mg/kg) in the drinking water or received drinking water only. Periodontitis was assessed when the ligatures had been in place for 14 d. RESULTS: Compared with control rats, PMX205- and PMX218-treated rats had significantly reduced periodontal bone loss. CONCLUSION: The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis.

Haemostatic devices in parotid surgery: a systematic review.

OBJECTIVE: The Harmonic Scalpel and Ligasure (Covidien) devices are commonly used in head and neck surgery. Parotidectomy is a complex and intricate surgery that requires careful dissection of the facial nerve. This study aimed to compare surgical outcomes in parotidectomy using these haemostatic devices with traditional scalpel and cautery. METHOD: A systematic review of the literature was performed with subsequent meta-analysis of seven studies that compared the use of haemostatic devices to traditional scalpel and cautery in parotidectomy. Outcome measures included: temporary facial paresis, operating time, intra-operative blood loss, post-operative drain output and length of hospital stay. RESULTS: A total of 7 studies representing 675 patients were identified: 372 patients were treated with haemostatic devices, and 303 patients were treated with scalpel and cautery. Statistically significant outcomes favouring the use of haemostatic devices included operating time, intra-operative blood loss and post-operative drain output. Outcome measures that did not favour either treatment included facial nerve paresis and length of hospital stay. CONCLUSION: Overall, haemostatic devices were found to reduce operating time, intra-operative blood loss and post-operative drain output.

Specimen oriented intraoperative margin assessment in oral cavity and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Evaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective case series and subsequent prospective cohort study SETTING: Tertiary care academic teaching hospital SUBJECTS AND METHODS: Retrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 - December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 - December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost. RESULTS: Analysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD. CONCLUSION: Implementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.

Prospective evaluation of laparoscopic pancreatic biopsies in 11 healthy cats.

BACKGROUND: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies. HYPOTHESIS: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology. ANIMALS: Eleven healthy female domestic shorthair cats. METHODS: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group. RESULTS: For all variables evaluated, there were no significant differences between biopsy and control cats. Re-evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high-quality pancreatic biopsy samples with an average size of 5 mm x 4 mm on 2-dimensional cut section. CONCLUSIONS AND CLINICAL IMPORTANCE: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.

Oncological and functional outcomes after repeat transoral laser microsurgery for the treatment of recurrent early glottic cancer.

BACKGROUND: Transoral laser microsurgery for glottic squamous cell carcinoma is the standard of care at many institutions. Repeat transoral laser microsurgery for recurrence may avoid the need for radiotherapy and total laryngectomy. This study aimed to identify oncological and functional outcomes in a cohort of patients who had undergone repeat transoral laser microsurgery procedures. METHOD: A retrospective review of prospectively collected data of patients treated with transoral laser microsurgery for carcinoma in situ or tumour stages T1 or T2 glottic cancer, from 2003 to 2018. RESULTS: Twenty patients were identified. Additional treatment was not needed in 45 per cent of patients. The five-year overall survival rate was 90 per cent. The disease-specific survival rate was 100 per cent. The laryngeal preservation rate was 85 per cent. There was improvement in mean Voice Handicap Index-10 scores following repeat transoral laser microsurgery treatment, when comparing the pre- and post-operative periods (mean scores = 15.5 vs 11.5, p = 0.373). CONCLUSION: Repeat transoral laser microsurgery can be an oncologically safe alternative to other salvage therapies for glottic squamous cell carcinoma recurrence, without sacrificing functional outcomes.

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy.

Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.

Longitudinal analysis of Voice Handicap Index in early glottic cancer patients treated with transoral laser microsurgery: age, gender, stage and time dependence.

OBJECTIVES: Transoral laser microsurgery is an increasingly common treatment modality for glottic carcinoma. This study aimed to determine the effect of age, gender, stage and time on voice-related quality of life using the Voice Handicap Index-10. METHODS: Primary early glottic carcinoma patients treated with transoral laser microsurgery were included in the study. Self-reported Voice Handicap Index testing was completed pre-operatively, three months post-operatively, and yearly at follow-up appointments. RESULTS: Voice Handicap Index improvement was found to be dependent on age and tumour stage, while no significant differences were found in Voice Handicap Index for gender. Voice Handicap Index score was significantly improved at 12 months and 24 months. Time versus Voice Handicap Index modelling revealed a preference for non-linear over linear regression. CONCLUSION: Age and stage are important factors, as younger patients with more advanced tumours show greater voice improvement post-operatively. Patient's Voice Handicap Index is predicted to have 95 per cent of maximal improvement by 5.5 months post-operatively.

Bacterial contamination of surgical loupes and headlights.

BACKGROUND: Medical equipment can transmit pathogenic bacteria to patients. This single-institution point prevalence study aimed to characterise the types and relative amount of bacteria found on surgical loupes, headlights and their battery packs. METHOD: Surgical loupes, headlights and battery packs of 16 otolaryngology staff and residents were sampled, cultured and quantified. Plate scores were summed for each equipment type, and the total was divided by the number of users to generate mean bacterial burden scores. Residents completed a questionnaire regarding their equipment cleaning practices. RESULTS: The contamination rates of loupes, headlights and battery packs were 68.75 per cent, 100 per cent and 75 per cent, respectively. Battery packs cultured more bacteria (1.58 per swab ± 1.00) than loupes (0.75 per swab ± 0.66; p = 0.024). Headlights had non-significantly greater growth (1.50 per swab ± 0.71) than loupes (p = 0.052). Bacterial growth was significantly higher from inner surfaces of loupes (p = 0.035) and headlights (p = 0.037). Potentially pathogenic bacteria were cultured from the equipment of five participants, including: Pantoea agglomerans, Acinetobacter radioresistens, Staphylococcus aureus, Acinetobacter calcoaceticus baumannii complex and Moraxella osloensis. CONCLUSION: This study demonstrates that surgical loupes and headlights used in otolaryngology harbour non-pathogenic skin flora and potentially pathogenic bacteria.

Role of complement C5a in mechanical inflammatory hypernociception: potential use of C5a receptor antagonists to control inflammatory pain.

BACKGROUND AND PURPOSE: C5a, a complement activation product, exhibits a broad spectrum of inflammatory activities particularly neutrophil chemoattraction. Herein, the role of C5a in the genesis of inflammatory hypernociception was investigated in rats and mice using the specific C5a receptor antagonist PMX53 (AcF-[OP(D-Cha)WR]). EXPERIMENTAL APPROACH: Mechanical hypernociception was evaluated with a modification of the Randall-Selitto test in rats and electronic pressure meter paw test in mice. Cytokines were measured by ELISA and neutrophil migration was determined by myeloperoxidase activity. KEY RESULTS: Local pretreatment of rats with PMX53 (60-180 microg per paw) inhibited zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception. These effects were associated with C5a receptor blockade since PMX53 also inhibited the hypernociception induced by zymosan-activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E(2) and dopamine. Underlying the C5a hypernociceptive mechanisms, PMX53 did not alter the cytokine release induced by inflammatory stimuli. However, PMX53 inhibited cytokine-induced hypernociception. PMX53 also inhibited the recruitment of neutrophils induced by zymosan but not by carrageenan or LPS, indicating an involvement of neutrophils in the hypernociceptive effect of C5a. Furthermore, the C5a-induced hypernociception was reduced in neutrophil-depleted rats. Extending these findings in rats, blocking C5a receptors also reduced zymosan-induced joint hypernociception in mice. CONCLUSIONS AND IMPLICATIONS: These results suggest that C5a is an important inflammatory hypernociceptive mediator, acting by a mechanism independent of hypernociceptive cytokine release, but dependent on the presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a has therapeutic potential in the control of inflammatory pain.

Fasciola hepatica: Histology of the testis in egg-producing adults of several laboratory-maintained isolates of flukes grown to maturity in cattle and sheep and in flukes from naturally infected hosts.

A total of 8 calves approximately 6 months old and 22 lambs of similar age were infected with metacercariae of Fasciola hepatica of various laboratory-maintained isolates including: Cullompton (sensitive to triclabendazole) and Sligo, Oberon and Leon (reported as resistant to triclabendazole). Ten to 16 weeks after infection, flukes were harvested from these experimental animals and the histology of the testis tissue was examined in a representative sample of flukes from each population. Adult wild-type flukes were also collected from 5 chronically infected cattle and 7 chronically infected sheep identified at post-mortem inspection. The testis tissue of these flukes was compared with that of the various laboratory-maintained isolates. Whilst the testes of the wild-type, Oberon and Leon flukes displayed all the usual cell types associated with spermatogenesis in Fasciola hepatica (spermatogonia, spermatocytes, spermatids and mature sperm), the Cullompton flukes from both cattle and sheep showed arrested spermatogenesis, with no stages later than primary spermatocytes represented in the testis profiles. The presence of numerous eosinophilic apoptotic bodies and nuclear fragments suggested that meiotic division was anomalous and incomplete. In contrast to the wild-type flukes, no mature spermatozoa were present in the testes or amongst the shelled eggs in the uterus. A high proportion of the eggs collected from these flukes hatched to release normal-appearing miracidia after an appropriate incubation period, as indeed was the case with all isolates examined and the wild-type flukes. It is concluded that the eggs of Cullompton flukes are capable of development without fertilization, i.e. are parthenogenetic. The implications of this for rapid evolution of resistant clones following an anthelmintic selection event are discussed. Amongst the Sligo flukes examined, two subtypes were recognised, namely, those flukes with all stages of spermatogenesis and mature spermatozoa present in the testes (type 1), and those flukes with all stages of spermatogenesis up to spermatids present, but no maturing spermatozoa in the testes (type 2). Each sheep infected with the Sligo isolate had both type 1 (approximately 60%) and type 2 (approximately 40%) flukes present in the population. Spermatozoa were found amongst the eggs in the uterus in 64% of flukes and this did not necessarily reflect the occurrence of spermatozoa in the testis profiles of particular flukes, suggesting that cross-fertilization had occurred. The apparent disruption of meiosis in the spermatocytes of the Cullompton flukes is consistent with reports that Cullompton flukes are triploid (3n=30), whereas the Sligo and wild-type flukes are diploid (2n=20). In the Sligo flukes the populations are apparently genetically heterogenous, with a proportion of the flukes unable to produce fully formed spermatozoa perhaps because of a failure in spermiogenesis involving elongation of the nucleus during morphogenesis.

Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predominantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase 'paradigm shift' in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and colleagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the management of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples' dogma makes his contribution truly a genuine paradigm shift.

Laryngeal recurrence sites in patients previously treated with transoral laser microsurgery for squamous cell carcinoma.

BACKGROUND: The laryngeal framework provides a natural barrier preventing tumour spread to extralaryngeal structures. Transoral laser microsurgery (TLM) for laryngeal squamous cell carcinoma (SCC) may violate these boundaries, altering the pathways of tumor spread for potential recurrences. Our project objective is to describe laryngeal SCC recurrence patterns and overall survival in patients requiring total laryngectomy (TL) after TLM. METHODS: Patients undergoing TLM for laryngeal SCC requiring salvage TL were identified from a prospective CO2 laser database containing all patients undergoing TLM for head and neck malignancies at the QEII Health Sciences Center in Halifax, Nova Scotia between March 2002 - May 2014. Surgical pathology reports were analyzed for tumor characteristics, extent of recurrence and invasion of local structures. Kaplan-Meier analyses were performed to evaluate overall survival, disease specific survival (DSS) and locoregional control. RESULTS: Fifteen patients were identified from the database as receiving salvage TL for recurrent disease after initial TLM resection for laryngeal SCC. Final pathology reports demonstrated that 67% (10/15) of patients had thyroid cartilage involvement while 53% (9/15) of patients had cricoid cartilage involvement on salvage TL pathology. 33% (5/15) of patients had perineural invasion and 27% (4/15) had lymphovascular invasion. Mean and median follow-up times were 36.7 months and 26.8 months respectively (range 3.9-112.6). The Kaplan-Meier estimate for overall survival at 36 months was 40% post TL with a standard error (SE) of 13.6%. DSS was 47% (SE 14.2%), and locoregional control was 55% (SE 14.5%) post TL. CONCLUSIONS: Laryngeal recurrence sites following TLM seem to be consistent with historical data at known laryngeal sites of vulnerability. Treatment with TLM does not predispose patients to a lower rate of locoregional control and overall survival after total laryngectomy and salvage outcomes are consistent with literature values.

Outcomes of transoral laser microsurgical management of T1b stage glottic cancer.

OBJECTIVE: This study aimed to evaluate the oncological and voice outcomes of transoral laser microsurgery for tumour stage T1b stage glottic cancer patients. METHODS: A prospective cohort study in a tertiary care head and neck cancer centre included tumour-node-metastasis stage T1bN0M0 glottic cancer patients scheduled to undergo transoral laser microsurgery from January 2002 until June 2014. Kaplan-Meier five-year analyses of local control, overall survival, disease-specific survival and laryngeal preservation were performed. Voice Handicap Index-10 scores and maximum phonation times were also recorded. RESULTS: Twenty-one participants with a mean age of 66.8 years were enrolled. The mean follow up was 56.5 months. Kaplan-Meier 5-year survival analysis illustrated a local control rate of 82 per cent, overall survival of 88 per cent, disease-specific survival of 100 per cent, and laryngeal preservation of 100 per cent. The pre-operative Voice Handicap Index-10 score was 19.1 ± 9.47 (mean ± standard deviation (SD)) and the post-operative scores were 13.5 ± 9.29 at three months, 10.44 ± 9.70 at one year and 5.83 ± 4.91 at two years. The pre-operative maximum phonation time was 16.23 ± 5.46 seconds (mean ± SD) and the post-operative values were 14.44 ± 6.73 seconds at three months, 15.27 ± 5.71 seconds at one year and 14.33 ± 6.44 seconds at two years. CONCLUSION: Transoral laser microsurgery yields relatively high rates of oncological control and acceptable voice outcomes, and thus shows utility as a primary treatment modality for T1b glottic cancer.

Prothrombotic factors enhance heparin-induced thrombocytopenia and thrombosis in vivo in a mouse model.

BACKGROUND: Heparin-induced thrombocytopenia/thrombosis (HIT/T) is a common cause of life- and limb-threatening thrombosis. The development of antibodies that react with complexes of heparin and platelet factor 4 (PF4) is fundamental to the development of the disease. However, anti-PF4/heparin antibodies are far more common than is HIT/T and there is less understanding of the factors that contribute to thrombosis in only a subset of patients. OBJECTIVES: Both qualitative and quantitative differences in multiple factors (e.g. antibodies, heparin and platelets) may influence the clinical course of patients who develop anti-PF4/heparin antibodies. We examined the hypothesis that host-specific factors, such as comorbid prothrombotic conditions, would exacerbate the pathologic effects of anti-PF4/heparin antibodies. METHODS AND RESULTS: A mouse model transgenic for human Fcgamma RIIa and PF4 and null for mouse PF4 was used to study the influence of prothrombotic conditions on the effects of anti-PF4/heparin antibodies in vivo. To simulate a prothrombotic milieu, mice were fed a hypercholesterolemic diet (HD). HD-fed mice had elevated plasma cholesterol, increased platelet reactivity and increased endothelial activation relative to mice fed a standard diet (SD). Age- and sex-matched mice from each diet group were treated with an anti-PF4/heparin antibody and heparin. HD-fed mice developed more severe thrombocytopenia than similarly treated SD-fed mice. Mice with moderate to severe thrombocytopenia had elevated plasma levels of thrombin-antithrombin complexes, indicative of increased thrombin generation in vivo. Platelet-fibrin thrombi were observed in multiple organs of HD-fed mice that developed severe thrombocytopenia. CONCLUSIONS: Host-specific factors, such as prothrombotic changes in platelet reactivity and/or endothelial activation, may influence the development of thrombosis in a subset of patients who develop anti-PF4/heparin antibodies.

The effect of a parenteral ivermectin/closantel injection on the growth and reproductive development of early immature Fasciola hepatica in cattle.

Sixteen calves approximately 6 months old were each infected with 500 metacercariae of Fasciola hepatica. Thirty-two days later they were weighed and divided into two groups, and on day 35 all calves in one of the groups were injected subcutaneously with an ivermectin/closantel combination. Both groups were sacrificed between days 70 and 72 to enable counting and examination of the flukes recovered from the bile ducts. Eggs released by the flukes were collected for incubation, hatching and estimation of egg viability. Flukes were counted, flat-fixed in 70% ethanol, stained with catechol and carmine and measured. The reproductive organs, namely testis, vitelline glands, ovary and uterus, were examined and scored on a 0-3 scale according to their state of development. This was visually assessed on the basis of size, distribution and staining density of their constituent tissues and the abundance of eggs in the uterus. A representative sample of flukes from each animal was fixed in formalin for histological sectioning to enable more detailed examination of the reproductive structures. Treatment of the immature flukes reduced the population in cattle by 42.6% as compared with the controls and as a result of the stunting effect due to the presence of closantel during early development the size of treated flukes was reduced by 43.9%. A bimodal pattern of size and reproductive score was also observed in flukes from treated cattle, suggesting that the stunting effect on individual flukes differed depending on whether or not they had gained access to the bile ducts or were still migrating in the hepatic parenchymal tissue at the time of drug exposure with the effect being greater once the fluke had gained access to the bile ducts. The mean reproductive score for untreated flukes was 8.76 and for treated flukes 5.64, a 35.6% reduction. This difference was highly significant (p<0.001). Egg shedding from treated flukes was significantly less than that from controls (p<0.05), but there were no differences in hatchability, suggesting that whilst drug treatment reduced the energy supply available for gametogenesis/oogenesis, it did not induce functional defects in the gonads or accessory reproductive organs. Histological examination confirmed that there was a reduction in development of testes, ovaries and vitellaria in treated flukes, with a consequent reduction in egg production. In the treated flukes, early spermatogonia and oogonia were the predominant cell types in the testes and ovary, whilst undifferentiated stem cells were abundant in the vitelline follicles. In untreated flukes, cells representing more advanced stages in gametogenesis and vitellogenesis predominated in the respective organs. It is likely that this inhibition of gametogenesis and vitellogenesis was caused by the effects of closantel treatment on intermediary metabolism in the flukes. Clearly these effects were evident even at a relatively early stage of fluke growth, and because of the impact on egg output may have epidemiological importance in addition to the reduction in fluke numbers.