Anatomic dissection of the arterial supply of the lips:an anatomical and analytical approach

Previous investigators have not described some of the new anatomic variations or provided quantitative and analytical data of the arterial anatomy of the lips in as much depth as in this study. Dissections of 14 different facial sides of cadavers were done. Through investigating the arterial supply of the upper and lower lips, measurements were performed and statistically analyzed. The main arterial supply of the upper lip was from the superior labial artery (SLA, mean external diameter, 1.8 mm [SD, 0.74 mm]); in addition, the subalar and septal branches contributed to its vascularization. The origin of the SLA was above the labial commissure in 78.6%. The subalar branch was not found but replaced by the alar artery that arose from the infraorbital artery in 1 specimen. The main arterial supply of the lower lip was derived from 3 branches of the facial artery, the inferior labial artery (mean external diameters, 1.4 mm [SD, 0.31 mm]) and the horizontal and vertical labiomental arteries. The inferior labial artery originated mostly below the labial commissure in 42.9% and formed a common trunk with the SLA in 28.6%. The horizontal labiomental artery was present in all, but vertical labiomental artery was absent in 21.4% of specimens. Overall, observed anatomic variations were classified into types I to VIII. Significant relations between the demographic variables and measured parameters were reported including the correlation coefficient among evaluated parameters. In conclusion, this study provides various information that aids in creating new flaps and supports the vascular base for clinical procedures in reconstructive surgery of the lip.

Calcification and ossification of the convexity of the falx cerebri and related subdural space in human cadavers

OBJECTIVE: The present work was planned to report the incidence of calcification and ossification of an isolated cranial dural fold. The form, degree of severity and range of extension of such changes will be described. Involvement of the neighboring brain tissue and blood vessels, whether meningeal or cerebral, will also be determined. The results of this study might highlight the occasional incidence of intracranial calcification and ossification in images of the head and their interpretation, by radiologists and neurologists, to be of dural or vascular origin.

METHODS: Two human formalin-fixed cadavers, one middle-aged female another older male, were investigated at the Anatomy Laboratory, College of Medicine, King Faisal University, Dammam, Kingdom of Saudi Arabia during the period from 2000 to 2003. In each cadaver, the skullcap was removed and the convexity of the cranial dura mater, as well as the individual dural folds, were carefully examined for any calcification or ossification. The meningeal and cerebral blood vessels together with the underlying brain were grossly inspected for such structural changes. Calcified or ossified tissues, when identified, were subjected to histological examination to confirm their construction.

RESULTS: The female cadaver showed a calcified parietal emissary vein piercing the skullcap and projecting into the scalp. The latter looked paler and deficient in hair on its right side. The base of the stump was surrounded by a granular patch of calcification. The upper convex border of the falx cerebri was hardened and it presented granules, plaques and a cauliflower mass, which all proved to be osseous in structure. The meningeal and right cerebral vessels were mottled with calcium granules. The underlying temporal and parietal lobes of the right cerebral hemisphere were degenerated. The male cadaver also revealed a calcified upper border of the falx cerebri and superior sagittal sinus. Osseous granules and plaques, similar to those of the first specimen, were also identified but without gross changes in the underlying brain.

CONCLUSION: Calcification or ossification of an isolated site of the cranial dura mater and the intracranial blood vessels might occur. These changes should be kept in mind while interpreting images of the skull and brain. Clinical assessment and laboratory investigations are required to determine whether these changes are idiopathic, traumatic, or as a manifestation of a generalized disease such as hyperparathyroidism, vitamin D-intoxication, or chronic renal failure.

Comparison of 5% versus 15% sucrose intakes as part of a eucaloric diet in overweight and obese subjects:effects on insulin sensitivity, glucose metabolism, vascular compliance, body composition and lipid profile. A randomised controlled trial

AIMS: The effect of dietary sucrose on insulin resistance and the pathogenesis of diabetes and vascular disease is unclear. We assessed the effect of 5% versus 15% sucrose intakes as part of a weight maintaining, eucaloric diet in overweight/obese subjects.

METHODS: Thirteen subjects took part in a randomised controlled crossover study (M:F 9:4, median age 46 years, range 37-56 years, BMI 31.7±0.9 kg/m(2)). Subjects completed two 6 week dietary periods separated by 4 week washout. Diets were designed to have identical macronutrient profile. Insulin action was assessed using a two-step hyperinsulinaemic euglycaemic clamp; glucose tolerance, vascular compliance, body composition and lipid profiles were also assessed.

RESULTS: There was no change in weight or body composition between diets. There was no difference in peripheral glucose utilization or suppression of endogenous glucose production. Fasting glucose was significantly lower after the 5% diet. There was no demonstrated effect on lipid profiles, blood pressure or vascular compliance.

CONCLUSION: A low-sucrose diet had no beneficial effect on insulin resistance as measured by the euglycaemic glucose clamp. However, reductions in fasting glucose, one hour insulin and insulin area under the curve with the low sucrose diet on glucose tolerance testing may indicate a beneficial effect and further work is required to determine if this is the case. Clinical Trial Registration number ISRCTN50808730.

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BACKGROUND: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.

METHODS: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.

RESULTS: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.

CONCLUSIONS: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Cancer survivors with self-reported late effects: their health status, care needs and service utilisation

OBJECTIVE: Cancer survivors (CSs) are at risk of developing late effects (LEs) associated with the disease and its treatment. This paper compares the health status, care needs and use of health services by CSs with LEs and CSs without LEs.

METHODS: Cancer survivors (n = 613) were identified via the Northern Ireland Cancer Registry and invited to participate in a postal survey that was administered by their general practitioner. The survey assessed self-reported LEs, health status, health service use and unmet care needs. A total of 289 (47%) CSs responded to the survey, and 93% of respondents completed a LEs scale.

RESULTS: Forty-one per cent (111/269) of CSs reported LEs. Survivors without LEs and survivors with LEs were comparable in terms of age and gender. The LEs group reported a significantly greater number of co-morbidities, lower physical health and mental health scores, greater overall health service use and more unmet needs. Unadjusted logistic regression analysis found that cancer site, time since diagnosis and treatment were significantly associated with reporting of LEs. CSs who received combination therapies compared with CSs who received single treatments were over two and a half times more likely to report LEs (OR = 2.63, 95% CI = 1.32-5.25) after controlling for all other variables.

CONCLUSIONS: The CS population with LEs comprises a particularly vulnerable group of survivors who have multiple health care problems and needs and who require tailored care plans that take account of LEs and their impact on health-related quality of life.

The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer

Aims: The utility of p53 as a prognostic assay has been elusive. The aims of this study were to describe a novel, reproducible scoring system and assess the relationship between differential p53 immunohistochemistry (IHC) expression patterns, TP53 mutation status and patient outcomes in breast cancer.

Methods and Results: Tissue microarrays were used to study p53 IHC expression patterns: expression was defined as extreme positive (EP), extreme negative (EN), and non-extreme (NE; intermediate patterns). Overall survival (OS) was used to define patient outcome. A representative subgroup (n = 30) showing the various p53 immunophenotypes was analysed for TP53 hotspot mutation status (exons 4-9). Extreme expression of any type occurred in 176 of 288 (61%) cases. As compared with NE expression, EP expression was significantly associated (P = 0.039) with poorer OS. In addition, as compared with NE expression, EN expression was associated (P = 0.059) with poorer OS. Combining cases showing either EP or EN expression better predicted OS than either pattern alone (P = 0.028). This combination immunophenotype was significant in univariate but not multivariate analysis. In subgroup analysis, six substitution exon mutations were detected, all corresponding to extreme IHC phenotypes. Five missense mutations corresponded to EP staining, and the nonsense mutation corresponded to EN staining. No mutations were detected in the NE group.

Conclusions: Patients with extreme p53 IHC expression have a worse OS than those with NE expression. Accounting for EN as well as EP expression improves the prognostic impact. Extreme expression positively correlates with nodal stage and histological grade, and negatively with hormone receptor status. Extreme expression may relate to specific mutational status.

Within-host evolution of Burkholderia pseudomallei over a twelve-year chronic carriage infection

UNLABELLED: Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is generally accepted that B. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. Over a 23-year study of melioidosis cases in Darwin, Australia, just one patient from 707 survivors has developed persistent asymptomatic B. pseudomallei carriage. To better understand the mechanisms behind this unique scenario, we performed whole-genome analysis of two strains isolated 139 months apart. During this period, B. pseudomallei underwent several adaptive changes. Of 23 point mutations, 78% were nonsynonymous and 43% were predicted to be deleterious to gene function, demonstrating a strong propensity for positive selection. Notably, a nonsense mutation inactivated the universal stress response sigma factor RpoS, with pleiotropic implications. The genome underwent substantial reduction, with four deletions in chromosome 2 resulting in the loss of 221 genes. The deleted loci included genes involved in secondary metabolism, environmental survival, and pathogenesis. Of 14 indels, 11 occurred in coding regions and 9 resulted in frameshift mutations that dramatically affected predicted gene products. Disproportionately, four indels affected lipopolysaccharide biosynthesis and modification. Finally, we identified a frameshift mutation in both P314 isolates within wcbR, an important component of the capsular polysaccharide I locus, suggesting virulence attenuation early in infection. Our study illustrates a unique clinical case that contrasts a high-consequence infectious agent with a long-term commensal infection and provides further insights into bacterial evolution within the human host.

IMPORTANCE: Some bacterial pathogens establish long-term infections that are difficult or impossible to eradicate with current treatments. Rapid advances in genome sequencing technologies provide a powerful tool for understanding bacterial persistence within the human host. Burkholderia pseudomallei is considered a highly pathogenic bacterium because infection is commonly fatal. Here, we document within-host evolution of B. pseudomallei in a unique case of human infection with ongoing chronic carriage. Genomic comparison of isolates obtained 139 months (11.5 years) apart showed a strong signal of adaptation within the human host, including inactivation of virulence and immunogenic factors, and deletion of pathways involved in environmental survival. Two global regulatory genes were mutated in the 139-month isolate, indicating extensive regulatory changes favoring bacterial persistence. Our study provides insights into B. pseudomallei pathogenesis and, more broadly, identifies parallel evolutionary mechanisms that underlie chronic persistence of all bacterial pathogens.