Location of the narrowest area of the pharynx regarding body mass index and obstructive sleep apnoea severity.

BACKGROUND: Among authors studying morphological determinants of the obstructive sleep apnoea (OSA) controversies exist on the location of the narrowest area within the pharynx, critical for development of obstruction. Those disagreements primarily revolve around differences between obese and nonobese OSA patients. Determination whether the location and size of the narrowest area within the pharynx differentiates the obese and nonobese OSA patients. MATERIALS AND METHODS: A population of 55 subjects was investigated after being diagnosed with OSA in the Polysomnography Laboratory of the Department and Clinic of Otolaryngology in the Medical University of Warsaw, Poland. Additionally a head computed tomography (CT) was performed in all the subjects. The CT images were used to do several crucial measurements which described the geometry of the facial skeleton as well as soft tissues of the head. The obtained results were correlated with apnoea-hypopnoea index (AHI) and body mass index (BMI) values. The data were statistically analysed. RESULTS: The distance between the hard palate and posterior pharyngeal wall parallel to the horizontal plane as well as the shortest distance between the soft palate and posterior pharyngeal wall significantly differentiated patients in the subgroups by AHI but not by BMI. CONCLUSIONS: Pharyngeal obstruction at the level of the hard and soft palate differentiates patients with severe OSA from patients with mild and moderate OSA regardless of BMI.

Anthropometric and physiologic assessment in sleep apnoea patients regarding body fat distribution.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by repeated episodes of pauses in breathing during sleep due to obstruction of the upper airway that result in transient hypoxaemia, sleep fragmentation and long-term cardiovascular disease. The most common risk factors for OSA include: obesity, age over 50 and neck circumference of more than 41 cm for females and more than 43 cm in males. Sleep apnoea is more common in men than in women. The aim of the conducted research was to evaluate relations between the anthropometric features connected with adipose tissue distribution and the severity of OSA. MATERIALS AND METHODS: The study was carried out on 180 patients (144 males and 36 females) diagnosed with OSA syndrome. The standard sleep parameters obtained from night polysomnography as well as skin-fat fold thickness and neck circumference and waist-to-hip ratio were analysed. Statistical analysis was performed using STATISTICA 10. RESULTS: It was stated that anthropometric parameters connected with the accu-mulation of adipose tissue in upper body were significantly related to severity of OSA in males (p ≤ 0.05). Body mass index (BMI) was significantly correlated with severity of OSA in females (p ≤ 0.05). CONCLUSIONS: In males, there is a connection between the severity of OSA, BMI and a higher accumulation of adipose tissue in upper part of the body measured by neck circumference and shoulder thickness of skin-fat folds, whereas in females only by BMI.

Morphological predictors of sleep apnoea severity.

BACKGROUND: Obstructive sleep apnoea (OSA) does not always depend on obesity but on a certain morphological configuration. The study objective was to verify a hypothesis about a relation between anthropometric features and OSA occurrence and severity. MATERIALS AND METHODS: The study involved 138 patients, who had reported in Department and Clinic of Otolaryngology, Warsaw Medical University, due to suspected OSA. Each patient underwent morphological evaluation according to visual analogue scales. The assessment involved nasal septum morphology evaluation according to a 4-grade scale, palate morphology evaluation according to the 4-grade Friedman scale, whereas the facial profile, oropharyngeal isthmus, and the shape of the nasopharynx were assessed according to our own 3-grade scale. RESULTS: Statistical analysis confirmed the high concordance of the basic polysomnographic parameters with the Friedman scale and the shape of the oropharyngeal isthmus. CONCLUSIONS: 1. The modified Mallampati score as well as evaluation of the shape of the oropharyngeal isthmus demonstrated high concordance with the basic polysomnographic parameters. 2. The neck circumference is a significant predictor of the apnoea-hypopnoea index value in males suffering from the OSA syndrome.

Biocompatibility of electrospun human albumin: a pilot study.

Albumin is rarely used for electrospinning because it does not form fibres in its native globular form. This paper presents a novel method for electrospinning human albumin from a solution containing pharmaceutical grade protein and 25% polyethylene oxide (PEO) used as the fibre-forming agent. After spontaneous cross-linking at body temperature, with no further chemicals added, the fibres become insoluble and the excess PEO can be washed out. Albumin deposited along the fibres retains its native characteristics, such as its non-adhesiveness to cells and its susceptibility for degradation by macrophages. To demonstrate this we evaluated the mechanical properties, biocompatibility and biodegradability of this novel product. After subcutaneous implantation in mice, albumin mats were completely resorbable within six days and elicited only a limited local inflammatory response. In vitro, the mats suppressed cell attachment and migration. As this product is inexpensive, produced from human pharmaceutical grade albumin without chemical modifications, retains its native protein properties and fulfils the specific requirements for anti-adhesive dressings, its clinical use can be expedited. We believe that it could specifically be used when treating paediatric patients with epidermolysis bullosa, in whom non-healing wounds occur after minor hand injuries which lead to rapid adhesions and devastating contractures.

Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study.

OBJECTIVE: Evaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women. DESIGN: Multicentre, open-label, long-term follow-up (NCT00947115) of a primary phase-III study (NCT00196937). SETTING: Six centres in Germany and Poland. POPULATION: 488 healthy women (aged 15-55 years, age-stratified into groups: 15-25, 26-45, and 46-55 years) who received three vaccine doses in the primary study. METHODS: Immune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) were measured by enzyme-linked immunosorbent assay (ELISA), and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) were recorded. MAIN OUTCOME MEASURES: Anti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1. RESULTS: At 6 years after dose 1, all women were seropositive for anti-HPV-16 and ≥97% were seropositive for anti-HPV-18 antibodies. GMTs ranged from 277.7 to 1344.6 EU/ml, and from 97.6 to 438.2 EU/ml, for anti-HPV-16 and anti-HPV-18, respectively. In all age groups, GMTs were higher (anti-HPV-16, 9.3-45.1-fold; anti-HPV-18, 4.3-19.4-fold) than levels associated with natural infection (29.8 EU/ml). A strong correlation between serum and CVS anti-HPV-16/18 levels was observed, with correlation coefficients of 0.81-0.96 (anti-HPV-16) and 0.69-0.84 (anti-HPV-18). Exploratory modelling based on the 6-year data predicted vaccine-induced anti-HPV-16/18 levels above natural infection levels for at least 20 years, except for anti-HPV-18 in the older age group (piecewise model). One vaccine-related and two fatal SAEs were reported. CONCLUSIONS: At 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups.

Mutations in Pol gene of hepatitis B virus in patients with chronic hepatitis B before and after therapy with nucleoside/nucleotide analogues.

Chronic hepatitis B (CHB) is one of the most common infections worldwide. Currently approved treatments of CHB include nucleoside/nucleotide analogues (NAs). However, long-term NA therapy is associated with accumulation of resistant mutations within the hepatitis B virus (HBV) polymerase gene. The incidence of naturally occurring HBV mutations leading to primary antiviral resistance has not been fully elucidated yet. The objective of present study was to detect the frequency of mutations within the HBV polymerase gene in 263 patients naïve to nucleoside/nucleotide analogues. Prevalence of HBV Pol gene mutations secondary to NA treatment in patients without pre-existing antiviral resistance mutations was also examined. Retrospective analysis showed that HBV Pol gene mutations were present in 7 out of 263 patients prior to the treatment. Mutations observed in NA-naïve CHB patients were associated only with resistance to lamivudine and adefovir. Compensatory mutations were observed as well. In the course of antiviral treatment, HBV Pol gene mutations were identified in 65 out of the remaining 256 CHB patients (25.39%), while no mutations of any type were detected in 160 patients (62.5%). The profiles of detected mutations were comparable to those observed in other studies that focused on the analysis of clinically relevant NA-resistant mutations. In conclusion, we found out that antiviral resistance mutations may pre-exist in the overall viral population present in untreated patients, although the incidence of HBV Pol gene mutations in NA-naïve CHB patients was low and reached only up to 2.66%. However, possible circulation and transmission of NAs-resistant HBV mutants in human population should be taken into account.

A nationwide analysis of risk factors for mortality and time to endoscopy in upper gastrointestinal haemorrhage.

BACKGROUND: We analysed nationwide in-patient data from 2002 to 2007 to determine significant demographic variables when predicting mortality and receipt of prompt oesophagogastroduodenoscopy (OGD) for acute variceal haemorrhage (AVH) and nonvariceal upper gastrointestinal haemorrhage (NVUGIH). AIM: To study the effects of demographic variables in predicting time to endoscopy and mortality in AVH and NVUGIH. METHODS: We analysed the United States' Nationwide Inpatient Sample (NIS), for risk factors for mortality and receipt of OGD within 1 day of admission for upper gastrointestinal haemorrhage. RESULTS: Risk factors for increased mortality in AVH included: age >60, men, African Americans, comorbidities, insurance type and delayed OGD. Risk factors for increased mortality in NVUGIH were similar to AVH, except race which was not significant. After correction for factors such as insurance type, comorbidity, hospital location and time to endoscopy, this increased risk of mortality persisted, suggesting that none of these factors was the primary cause of the observed differences. For AVH, OGD within 1 day of admission was more likely in men, White Americans, patients aged 18-40 years, privately insured and those with no comorbidities. OGD within 1 day of admission in NVUGIH was more likely in men, patients age 40-60, Whites, Hispanics, privately insured and those with a single comorbidity. CONCLUSIONS: In multivariate analysis, in-patient mortality in AVH and NVUGIH increased with age, comorbidity, male gender, and delayed time to endoscopy. Young, healthier men were most likely to receive OGD within 1 day of admission. African Americans were less likely to receive OGD within 1 day of admission and had increased mortality in cases of AVH.

Prediction of pneumococcal conjugate vaccine effectiveness against invasive pneumococcal disease using opsonophagocytic activity and antibody concentrations determined by enzyme-linked immunosorbent assay with 22F adsorption.

We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 µg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 µg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.

Use of trans-septal mattress suture of Little's area for anterior epistaxis.

BACKGROUND: In some cases of epistaxis, anterior packing and/or electrocoagulation are not sufficient and suturing is needed. However, standard suturing techniques are sometimes ineffective. This paper reports the use of a new kind of trans-septal mattress suture, based on regional vascular anatomy, in this clinical context. METHODS: Four adult patients with haemorrhage in Little's area underwent standard suturing, but bleeding persisted. These patients were successfully treated with trans-septal mattress suturing, using four punctures around the haemorrhage site. RESULTS: No relapses or complications were observed over a six-month follow-up period. CONCLUSION: In cases of persistent bleeding from Little's area, suturing should surround the bleeding area. The described suturing method is simple, efficacious and cheap.

Randomised, controlled trial of concomitant pneumococcal and meningococcal conjugate vaccines.

A randomised, open-label study compared the immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) and meningococcal C conjugate vaccine (MnCC vaccine) administered concomitantly and individually. Infants received PCV7+MnCC vaccine (n=265), PCV7 alone (n=268) or MnCC vaccine alone (n=178). PCV7 was administered at 2, 3½, 6 and 12 months, and MnCC vaccine at 2, 6 and 12 months. For the 7 pneumococcal serotypes tested (4, 6B, 9V, 14, 18C, 19F and 23F), proportions of subjects with pneumococcal serotype-specific immunoglobulin G (IgG) antibody concentrations ≥0.35 µg/mL post-infant series were non-inferior for the PCV7+MnCC vaccine (91.5-99.6%) and PCV7 (89.0-99.6%) groups. Proportions of subjects achieving serogroup C meningococcal serum bactericidal assay titres ≥1:8 post-infant series were non-inferior for the PCV7+MnCC vaccine (99.6%) and MnCC vaccine groups (98.8%). Pneumococcal IgG antibody levels were similar in the PCV7+MnCC vaccine and PCV7 groups at each time point. Post-infant and post-toddler meningococcus C serum bactericidal assay titres and IgG levels were similar in the PCV7+MnCC vaccine and MnCC groups, although pre-toddler, the levels were lower in the PCV7+MnCC vaccine group than the MnCC vaccine group. Immune response rates to diphtheria antigen approached 100% for all vaccine groups. Local reactions were mostly similar among the treatment groups. The MnCC vaccine group had lower rates of some systemic events than the PCV7+MnCC vaccine group. Immune responses to PCV7+MnCC vaccine were non-inferior compared with those seen with each vaccine administered alone.

Topographical anatomy and morphometry of the temporal bone of the macaque.

Based on the dissections of 24 bones of 12 macaques (Macaca mulatta), a systematic anatomical description was made and measurements of the chosen size parameters of the temporal bone as well as the skull were taken. Although there is a small mastoid process, the general arrangement of the macaque's temporal bone structures is very close to that which is observed in humans. The main differences are a different model of pneumatisation and the presence of subarcuate fossa, which possesses considerable dimensions. The main air space in the middle ear is the mesotympanum, but there are also additional air cells: the epitympanic recess containing the head of malleus and body of incus, the mastoid cavity, and several air spaces on the floor of the tympanic cavity. The vicinity of the carotid canal is also very well pneumatised and the walls of the canal are very thin. The semicircular canals are relatively small, very regular in shape, and characterized by almost the same dimensions. The bony walls of the labyrinth are relatively thin.

The size of venous foramina and skull capacity in man and selected vertebrate species.

In many experiments it was proved that brain cooling systems in mammals and birds depend on the flow of the cool venous blood into the cranial cavity through a well-developed system of foramina. In order to investigate the anatomical basis of this mechanism a morphological study was undertaken. On 10 species of mammals and birds, a correlation between the skull capacity and the size of its main venous foramina was determined. A computer system of image analysis was used. In man the skull that was the largest, however consisted venous foramina of the smallest size. Moreover, the asymmetry of the foramina and the concentration of the outflow in one dominant foramen was the greatest. Probably the dominance of only one venous foramen on each side of the human skull provides the reduction of flow resistance and creates more advantageous conditions for blood outflow from the skull, and therefore, better conditions for brain cooling.

Topographical anatomy and measurements of selected parameters of the rat temporal bone.

On the basis of dissection of 24 bones of 12 black rats a systematic anatomical description was made and measurements of selected size parameters of the temporal bone were taken. Besides the main air space in the middle ear, the tympanic bulla, there are also additional air cells, namely the anterior and posterior epitympanic recesses, containing the head of the malleus and the body of the incus. On the side of the epitympanic recesses the following are easily accessible: the malleus head and the core of the incus, the superior and lateral semicircular canals and the facial nerve. On the side of the ventral tympanic bulla it is easy access to both windows and the cochlea. The semicircular canals are relatively large, the lateral canal being the largest and the posterior the smallest. The length of the spiral canal of the cochlea does not exceed 11 mm. It is worth mentioning that both the vertical and horizontal dimensions of the scala vestibuli and scala tympani do not even exceed 0.7 mm in the basal turn, and are significantly decreased to tenths of a millimetre in further turns. This needs to be taken into consideration during all experiments requiring the introduction of examining instruments into the cochlear scala.

A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial.

OBJECTIVE: To study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR). DESIGN: A phase 3 open randomised controlled trial. SETTING: One centre in Oxford, UK and nine centres in Poland. SUBJECTS: 12-15-month-old healthy children. INTERVENTIONS: In the primary stage of the study 500 healthy 6-12-week-old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT+DTPa-IPV or MenC-CRM197 vaccine+DTPa-IPV-Hib. In the booster stage, 476 participants (190 in the UK and 286 in Poland) were vaccinated with Hib-MenC-TT and MMR. MAIN OUTCOME MEASURES: The proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose. RESULTS: The co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children vaccinated with Hib-MenC-TT+DTPa-IPV or MenC-CRM197+DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (lower limit of (LL) 95% CI 92.4) of participants had rSBA-MenC >or=1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations >or=1.0 microg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95% CI 6.2 to 19.4). CONCLUSION: The waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease. TRIAL REGISTRATION NUMBER: NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).

ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice.

Angiotensin converting enzyme 2 (ACE2) is localized to the glomerular epithelial cells. Since ACE2 promotes the degradation of angiotensin II, a decrease in ACE2 activity could lead to the development of glomerular injury. We gave a specific ACE2 inhibitor, MLN-4760, for 4 weeks to mice rendered diabetic with streptozotocin. The urinary albumin/creatinine ratio was increased along with expansion of the glomerular matrix in diabetic mice treated with the inhibitor compared to the vehicle-treated mice. Glomerular staining of ACE was increased in the diabetic group and was further significantly increased in the diabetic group treated with MLN-4760. In renal vessels, ACE expression was also increased in the diabetic mice and, again, further increased in those diabetic mice treated with the ACE2 inhibitor. Our study shows that chronic pharmacologic ACE2 inhibition worsens glomerular injury in streptozotocin-induced diabetic mice in association with increased ACE expression.

The size of selected human skull foramina in relation to skull capacity.

An anatomical study was undertaken in order to investigate whether the sizes of selected human skull foramina with significant venous compartments correlated significantly with skull capacity. A total of 100 macerated human skulls were examined to determine the diameter of the foramina and the skull capacity. Measurements of the surface area of the foramina were made using a computerised digital analysis system. Only the size of the hypoglossal canal and jugular foramen were found to correlate significantly with the capacity of the skull. This correlation, together with the considerable size of the hypoglossal canal, indicated its important role in the venous drainage of the brain. There was considerable centralisation of venous outflow from the brain, with 60% of the area of all venous foramina of the skull occupied by jugular foramina. Asymmetry between the right and left jugular foramina was identified, with an average ratio of 1.6 (ranging between 1 and 3.47). In the case of right-sided domination the correlation between the skull capacity and the size of both jugular foramina was negative (the larger the skull cavity, the less the asymmetry), while in the case of left-sided domination the correlation was positive. Perhaps the left-sided domination is less advantageous for the haemodynamics of blood outflow, as the left brachiocephalic vein is longer and is often compressed by the sternum and aortic arch.

The anatomy of the tympanic sinus.

The tympanic sinus is one of the most important structures of the human temporal bone. Located in its vicinity are the round window, posterior semicircular canal and facial nerve. The study was performed on 30 temporal bones taken from adult cadavers of both sexes. After the tympanic sinus had been identified, its morphological features were evaluated. The sinus was then measured using a graticule with an accuracy of 0.05 mm. Also measured were the shortest distances from the tympanic sinus to the neighbouring structures (the lateral and posterior semicircular canal, the facial nerve canal and the jugular fossa). The measurements were performed under a surgical microscope with eye-piece graduation of 0.05 mm accuracy. Four main morphological types of fossa of the tympanic sinus and two main developmental forms, a deep sinus and a shallow sinus, were distinguished. The existence of a deep sinus was associated with absence of the bridge and the sinus was shallower when the bridge was prominent. The very deep sinuses were located close to the facial canal, in some cases penetrating deep in its vicinity (in some cases even going beyond two thirds of the canal's circumference), which poses a real risk of facial nerve damage during surgical removal of a lesion located in close proximity to the nerve. In most cases the tympanic sinus is elliptical in shape and its long diameter lies in the vertical plane (mean value: 2.73 x 2.23 mm). The mean distances from the tympanic sinus to the facial nerve canal, lateral semicircular canal, posterior semicircular canal and jugular fossa were 1.5 mm, 2.1 mm, 1.59 mm and 5.5 mm respectively. No correlation was observed between the measurement results and either sex or side.

The occurrence, variations and diameter of the human condylar canal in relation to the jugular foramen.

In medical practice, especially in analysis of radiograms and computed tomography scans, it is very important to be familiar with the anatomy of the skull base, not only the normal and typical anatomical structures but also the variations and anomalies. One of the important venous foramina of the human skull is the condylar canal. This structure is described as the most stable and permanent venous emissary, with a prevalence of up to 100%. In our study, based on 100 human macerated skulls, this canal was encountered in 81% of cases. In several it was double. We have not encountered any information on this in the available literature. We found that the condylar canal in humans could be double and that the size of the external opening of this canal is not crucial in relation to the size of the jugular foramen. There was no significant correlation between the jugular foramen and the condylar canal in our specimens.

Abdominal radiation exposure elicits inflammatory responses and abscopal effects in the lungs of mice.

An inflammatory reaction is a classical feature of radiation exposure and appears to be a key event in the development of the acute radiation syndrome. We have investigated the radiation-induced inflammatory response in C57BL6/J mice after total abdominal or total-body irradiation at a dose of 15 Gy. Our goal was to determine the radiation-induced inflammatory response of the gut and to study the consequences of abdominal irradiation for the intestine and for the lungs as a distant organ. A comparison with total-body irradiation was used to take into account the hematopoietic response in the inflammatory process. For both irradiation regimens, systemic and intestinal responses were evaluated. A systemic inflammatory reaction was found after abdominal and total-body irradiation, concomitant with increased cytokine and chemokine production in the jejunum of irradiated mice. In the lungs, the radiation-induced changes in the production of cytokines and chemokines and in the expression of adhesion molecules after both abdominal and total-body irradiation indicate a possible abscopal effect of radiation in our model. The effects observed in the lungs after irradiation of the abdomino-pelvic region may be caused by circulating inflammatory mediators consequent to the gut inflammatory response.