Multimodal analgesia using intrathecal diamorphine, and paravertebral and rectus sheath catheters are as effective as thoracic epidural for analgesia post-open two-phase esophagectomy within an enhanced recovery program.

Thoracic epidural (TE) analgesia has been the standard of care for transthoracic esophagectomy patients since the 1990s. Multimodal anesthesia using intrathecal diamorphine, local anesthetic infusion catheters (LAC) into the paravertebral space and rectus sheaths and intravenous opioid postoperatively represent an alternative option for postoperative analgesia. While TE can provide excellent pain control, it may inhibit early postoperative recovery by causing hypotension and reducing mobilization. The aim of this study is to determine whether multimodal analgesia with LAC was effective with respect to adequate pain management, and compare its impact on hypotension and mobility. Patients receiving multimodal LAC analgesia were matched using propensity score matching to patients undergoing two-phase trans-thoracic esophagectomy with a TE over a two-year period (from January 2015 to December 2016). Postoperative endpoints that had been evaluated prospectively, including pain scores on movement and at rest, inotrope or vasoconstrictor requirements, and hypotension (systolic BP < 90 mmHg), were compared between cohorts. Out of 14 patients (13 male) that received LAC were matched to a cohort of 14 patients on age, sex, and comorbidity. Mean and maximum pain scores at rest and movement on postoperative days 0 to 3 were equivalent between the groups. In both cohorts, 50% of patients had a pain score of more than 7 on at least one occasion. Fewer patients in the LAC group required vasoconstrictor infusion (LAC: 36% vs. TE: 57%, P = 0.256) to maintain blood pressure or had episodes of hypotension (LAC: 43% vs. TE: 79%, P = 0.05). The LAC group was more able to ambulate on the first postoperative day (LAC: 64% vs. TE: 43%, P = 0.14) but these differences were not statistically significant. Within the epidural cohort, three patients had interruption of epidural due to dislodgement or failure of block compared to no disruption in the multimodal local anesthesia catheters group (P = 0.05). Therefore, multimodal anesthesia using spinal diamorphine with combined paravertebral and rectus sheath local anesthetic catheters appears to provide comparable pain relief post two-phase esophagectomy and may provide more reliable and safe analgesia than the current standard of care.

A comparison of grades awarded by peer assessment, faculty and a digital scanning device in a pre-clinical operative skills course.

OBJECTIVE: The aim of this study was to compare the grades awarded by two experienced assessors with peer-assessment marks and measurements from a digital scanning device (Prepassistant; KaVo, Biberach, Germany), for full gold crown preparations completed in a pre-clinical operative skills course on typodont teeth. METHODS: Seventy-eight preparations on typodont teeth were randomised and assessed by all three methods. Agreement was measured using weighted kappa statistics, and mean rank scores given by the Friedman test. RESULTS: The highest agreement was seen between the experienced assessors (0.38), closely followed by peer assessment and experienced assessor agreement (0.36, 0.29). Despite this, the results indicate poor levels of agreement. No agreement was seen between any of the assessment methods when compared to the digital scanning device. CONCLUSIONS: The findings of this study could be related to the difficulty of calculating a single grade from the output of the device, in addition to the inability of the machine to assess all the factors necessary for an acceptable preparation. From this study, it can be concluded that this device is not suitable for calculating grades when used in isolation. Further research could explore the role of the Prepassistant in providing student feedback, its potential to enhance the learning experience and the subsequent effect on performance.

Early mental health morbidity and later smoking at age 17 years.

BACKGROUND: We examined the relationship between the onset and pattern of childhood mental health disorders and subsequent current smoking status at age 17 years. METHOD: Data were from a prospective cohort study of 2868 births of which 1064 supplied information about their current smoking at 17 years of age. The association between the onset and pattern of clinically significant mental health disorders in the child and subsequent smoking at age 17 years was estimated via multivariable logistic regression. RESULTS: Relative to 17 year olds who never had an externalizing disorder, 17-year-olds who had an externalizing disorder at age 5, 8 or 14 years were, respectively, 2.0 times [95% confidence interval (CI) 1.24-3.25], 1.9 (95% CI 1.00-3.65) or 3.9 times (95% CI 1.73-8.72) more likely to be a current smoker. Children with an ongoing pattern of externalizing disorder were 3.0 times (95% CI 1.89-4.84) more likely to be smokers at the age of 17 years and those whose mothers reported daily consumption of 6-10 cigarettes at 18 weeks' gestation were 2.5 times (OR 2.46, 95% CI 1.26-4.83) more likely to report smoking at 17 years of age. Associations with early anxiety and depression in the child were not found. CONCLUSIONS: Current smoking in 17-year-olds may be underpinned by early emergent, and then, ongoing, externalizing disorder that commenced as young as age 5 years as well as exposure to early prenatal maternal smoking. The associations documented in adults and adolescents that link tobacco smoking and mental health are likely to be in play at these early points in development.

Nitric oxide and TNF-alpha trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice.

Recombinase-activating gene-2-deficient (Rag2(-/-)) mice lacking functional lymphocytes provide a useful model of chronic inflammatory bowel disease-emulating events in human colon cancer. Infection of Rag2(-/-) mice with Helicobacter hepaticus led to accumulation of macrophages and neutrophils in the colon, a process temporally related to up-regulation of tissue inducible nitric oxide synthase (iNOS) expression at the site of infection and increased nitric oxide (NO) production, as evidenced by urinary excretion of nitrate. Progressive development of increasingly severe inflammation, hyperplasia, dysplasia, and cancer accompanied these changes. Concurrent administration of an iNOS inhibitor prevented NO production and abrogated epithelial pathology and inhibited the onset of cancer. The presence of Gr-1(+) neutrophils and elevated tumor necrosis factor-alpha (TNF-alpha) expression in colon were required for increased iNOS expression and cancer, whereas interleukin-10 (IL-10) down-regulated TNF-alpha and iNOS expression and suppressed cancer. Anti-inflammatory CD4(+) regulatory lymphocytes also down-regulated iNOS and reduced cancer formation. Collectively, these results confirm essential roles for inflammation, increased TNF-alpha expression, and elevated NO production in colon carcinogenesis.

Successful reversal of threatening carotid artery occlusion in HIV-associated non-aneurysmal vasculitis.

We report a case of HIV-associated carotid vasculitis, causing cerebral infarction. Immediate corticosteroid treatment was followed by improvement, with radiological documentation of reversal of the vasculitic changes, preventing arterial occlusion. Vasculitis should be considered as a diagnosis in stroke in HIV and steroid treatment considered as a potentially life-saving intervention.

Restorative aspects of oral cancer reconstruction.

The oral rehabilitation of head and neck cancer patients is a vital and pivotal part of their care pathway, helping to restore function, aesthetics and improve patient well-being and quality of life. Patient-reported outcome data demonstrates that such patients consider that many of their continued and unmet needs relate to their oral and dental rehabilitation. It is therefore incumbent on all dental team members to be aware of the entire spectrum of restorative management options that can be utilised in both the prevention and rehabilitation of this patient cohort. The literature highlights that maxillary and mid-face tumours are challenging, as patients often suffer both profound functional and aesthetic consequences with significant physiological and psychological impact. Conversely, mandibular and floor of mouth tumours often result in issues primarily affecting oral function. This paper will summarise commonly encountered functional and aesthetic issues facing the restorative dental team and highlight widespread preventive challenges.

c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene.

The mechanisms through which the oncoprotein c-Myc initiates locus-specific gene amplification are not understood. When analysing the initiation mechanism of c-Myc-dependent amplification of the mouse ribonucleotide reductase R2 (R2) gene, we observe c-Myc-dependent initiation of illegitimate DNA replication of the R2 gene. We demonstrate multiple simultaneous c-Myc-induced R2 replication forks, whereas R2 normally replicates with a single fork. In contrast, cyclin C replicates with only a single replication fork irrespective of c-Myc deregulation. In addition to de novo replication forks, c-Myc also initiates bi-allelic replication of R2, abrogating its normal mono-allelic replication pattern. Moreover, several chromosomal regions also display c-Myc-induced illegitimate replication profiles. Thus, c-Myc can act as an illegitimate replication-licensing factor that promotes de novo replication initiation and illegitimate replication timing that adversely impacts upon genomic stability.

Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis.

A spectrum of left ventricular diastolic filling abnormalities noted on Doppler echocardiography has been demonstrated in patients with cardiac amyloidosis. To determine how these filling abnormalities evolve over time and the significance of any change, serial pulsed wave Doppler studies of left ventricular inflow were performed over 12.6 +/- 4.9 months in 41 consecutive patients (36 men and 15 women, mean age 59 +/- 11 years) with typical two-dimensional echocardiographic features of cardiac involvement. The measurements were peak left ventricular inflow in early diastole (E) and atrial contraction (A) velocities, E/A ratio, deceleration time and isovolumetric relaxation time. Patients were classified by mean left ventricular wall thickness into an early group (less than 15 mm) of 24 patients and an advanced group (greater than or equal to 15 mm) of 17 patients. The total group showed an increased E/A ratio (1.7 +/- 0.9 versus 1.4 +/- 0.9, p = 0.009) and decreased deceleration time (164 +/- 57 versus 174 +/- 51 ms, p = 0.11) at follow-up compared with baseline study. The early group showed significant changes in the E/A ratio (1.6 +/- 1.0 versus 1.2 +/- 0.7, p = 0.001) between the two studies. Seven patients (29%) in the early group showed a change from an abnormal relaxation or "normal" pattern to one of restriction, coincident with increased symptoms in six of these patients. Fifteen (88%) of the 17 patients in the advanced group did not show significant changes in the measures during the follow-up study, but these patients already showed a restrictive pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Professional behaviours demonstrated by undergraduate dental students using an incident reporting system.

Critical incident reporting is widely used across healthcare and other sectors for reporting adverse events or behaviours. More recently it has been used in medical education as a means of assessing student professionalism. The aims of this study were to determine the usage of critical incident forms when reporting behaviours related to professionalism demonstrated by undergraduate dental students, and the types of behaviours exhibited. Three types of form could be awarded for highly professional (green), minor unprofessional (yellow) and serious unprofessional (red) behaviours. All forms completed over a two-year period were analysed recording the year of student, type of card and demographic of the member of staff reporting the incident. All text relating to the nature of the incident was entered into a qualitative data analysis software package and analysed thematically. In total, 583 cards were awarded, 55% green, 34% yellow and 11% red. Seventy-four percent of cards were awarded in a clinical environment, with administrative staff using them the most (29%). The overwhelming professional behaviours demonstrated related to altruism. The most common unprofessional behaviours related to a lack of conscientiousness, although a greater range of common unprofessional behaviours were reported. In conclusion, critical incidents forms were widely used for reporting both professional and unprofessional behaviours particularly in clinical environments by a range of staff. Such forms may be a valuable addition to the professionalism assessment portfolio, capturing behaviours not previously reported using traditional methods.

Myelitis following chickenpox: a case report.

An 18-year-old woman presented with myelopathic symptoms and a T-8 sensory deficit during a primary varicella infection. There were significant MRI changes in both the cervical and thoracic regions. Following treatment with steroids and intravenous acyclovir, the patient improved clinically and the abnormalities on MRI improved.

Good clinical outcome in a patient with a large CT scan hypodensity treated with intra-arterial urokinase after an embolic stroke.

Hypodense regions demonstrated by CT within 6 hours of the onset of stroke may reflect irreversibly damaged tissue, and some have suggested that patients with such findings should be spared the risks of thrombolytic therapy since they are unable to benefit from it. We report here a patient with a low-density area demonstrated by CT less than 6 hours after onset of symptoms who improved dramatically after successful intra-arterial thrombolysis.

Incidence of renal anomalies in children prenatally exposed to ethanol.

OBJECTIVE: Based on a number of studies involving animals as well as human case reports indicating an association between prenatal ethanol exposure and renal malformations, it has been suggested that children with fetal alcohol syndrome (FAS) should be screened for renal anomalies. The purpose of this study was to evaluate a group of children prenatally exposed to alcohol to determine the incidence of renal anomalies and to evaluate the need for such a screening procedure. METHODS: Renal ultrasounds were performed on a total of 84 patients (68 children, 13 adolescents, and three adults). In addition to screening for malformations, renal size was studied. Data were analyzed using both chronologic and height-age as determinants of kidney size. PATIENTS: Of these 84 patients, 51 (61%) had FAS, and 33 (39%) had a history of prenatal ethanol exposure but did not have FAS. RESULTS: Three (3.6%) patients (one with FAS, two with prenatal ethanol exposure who did not have FAS) had significant renal abnormalities. This incidence was not significantly different from that found in ultrasound screening of newborns. The kidneys of children with both FAS and prenatal ethanol exposure who did not have FAS were significantly smaller than normal for both chronologic and height-age. When children were compared across chronologic ages, those with FAS had significantly smaller kidneys than those who had no evidence of FAS. After adjusting for height, the difference between these two groups was no longer significant. CONCLUSIONS: Based on these data, children prenatally exposed to ethanol do not need to be screened for renal anomalies.

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man.

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.

Impairment of cingulothalamic learning-related neuronal coding in rabbits exposed to cocaine in utero: general and sex-specific effects.

Neuronal activity was recorded in the cingulate cortex and the limbic thalamus in Dutch-belted rabbits (Oryctolagus cuniculus) exposed to cocaine (8 mg/kg/day i.v.) or saline in utero during acquisition and reversal learning of a discriminative avoidance response. Anterior cingulate cortical excitatory training-induced activity (TIA) was attenuated in cocaine-exposed female rabbits during acquisition and reversal learning, but only during reversal learning in male rabbits. Posterior cingulate cortical excitatory TIA was lessened in cocaine-exposed rabbits during acquisition, whereas discrimination between the positive and negative cues was enhanced. Neuronal firing was attenuated in the anterior ventral thalamus in cocaine-exposed rabbits during acquisition and reversal learning. Behavioral learning was normal in cocaine-exposed rabbits. Other data suggest that rabbits exposed to cocaine in utero exhibit a learning deficit when trained with nonsalient cues.

Improved lung preservation with cold air storage.

Conventional topical slush cooling limits lung transport to 4 to 6 hours. For this canine study of an alternate air cooling system, 37 canine lungs were removed: 24 were placed in plastic bags, and inserted in a Transplanthermm container at core air temperatures (n = 6 lungs each) of (A) 4 degrees C, (B) 8 degrees C, (C) 12 degrees C, and (D) 20 degrees C; 6 were stored conventionally in ice slush (E); and 7 were transplanted immediately (F). After 8 hours, the stored lungs were transplanted and the contralateral pulmonary artery was ligated. Survival, arterial oxygen tension, and extravascular lung water were monitored at 15 minutes and every hour for 4 hours. Four-hour survival was 100% in groups A, B, and F; 83% in group C, 50% in group D, and 17% in group E. The mean arterial oxygen tension at 1 hour was lower in group E (6.4 +/- 2.4 kPa) than in group A (39.8 +/- 13.2 kPa) (p = 0.0002) or in group F (42.0 +/- 16.2 kPa) (p = 0.0035). Extravascular lung water in group E was higher at 15 minutes (15.44 +/- 5.63 mL/kg) than in group A (3.76 +/- 0.63 mL/kg) (p = 0.0001) and group F (4.69 +/- 1.65 mL/kg) (p = 0.003). Cold air storage appears to provide better lung preservation than hypothermic immersion in ice slush.

Age-related prevalence of valvular regurgitation in normal subjects: a comprehensive color flow examination of 118 volunteers.

We prospectively assessed the influence of aging on the prevalence of valvular regurgitation by using color flow imaging. One hundred eighteen healthy volunteers (21 to 82 years old) had a two-dimensional Doppler echocardiographic study that included color flow imaging to assess valvular regurgitation and that was semiquantitated by mapping the dimensions of the color flow regurgitant jet in orthogonal views. The subjects were divided into two groups: group 1 consisted of subjects who were younger than 50 years old (n = 61), and group 2 consisted of subjects who were at least 50 years old (n = 57). Mitral regurgitation was detected in 57 (48%) of the 118 subjects: 24 subjects (39%) in group 1 and 33 subjects (58%) in group 2. The severity of mitral regurgitation was trivial to mild. Aortic regurgitation was detected in 13 (11%) of the 118 subjects, all in group 2. The severity was trivial to mild. Tricuspid regurgitation was detected in 77 (65%) of the 118 subjects: 35 (57%) in group 1 and 42 (74%) in group 2. The severity was trivial to mild. Pulmonary regurgitation was detected in 24 (31%) of 78 subjects: nine (22%) in group 1 and 15 (41%) in group 2. The severity was trivial. These findings suggest that valvular regurgitation of a trivial or mild degree is a frequent finding in normal subjects and that it increases with age.

Aortic dissection: review of value and limitations of two-dimensional echocardiography in a six-year experience.

The utility of transthoracic two-dimensional echocardiography in patients with aortic dissection was assessed by retrospective analysis in 67 patients: 31 patients with DeBakey type I, 21 patients with type II, 10 patients with type III, and five patients with false-positive diagnoses. Aortic dissection was correctly identified by two-dimensional echocardiography in 49 patients; 13 had false-negative diagnoses. Therefore the sensitivity was 79%, and the positive predictive accuracy was 91%. Transthoracic two-dimensional echocardiography is a reasonable screening technique for diagnosis of aortic dissection.

Level of agreement between questionnaire measures of alcohol dependence, alcoholism and problem drinking in a sample presenting at a specialist alcohol treatment service.

Two questionnaire measures of the alcohol dependence syndrome, one of alcoholism, and one of alcohol-related problems were compared in a sample of 101 subjects attending a specialist alcohol treatment unit. There was substantial agreement between the two measures of alcohol dependence, and lesser agreement between any other pairing. The measures of alcohol dependence also showed the strongest correlation with reported weekly alcohol consumption. The findings are compared with previous research, and the suitability of the various questionnaires as case-defining instruments in empirical investigations is discussed.

Temporary vessel occlusion during intracranial aneurysm repair.

Any method that decreases the risk of intraoperative rupture should improve outcome if complications associated with its use do not negate positive effect. If application time is limited and a form of cerebral protection and appropriate monitoring of cerebral function are used, temporary clip application may meet these requirements. The efficacy of temporary occlusion as an adjunct to aneurysm clipping may be limited by technical considerations with respect to regional anatomy, aneurysm size, and aneurysm consistency. In areas of limited access, positioning proximal clips may not be feasible. The use of endovascular techniques of balloon occlusion may provide proximal control in these situations (9, 106). The decision to use total circulatory arrest and profound hypothermia, as opposed to temporary clip application, remains largely a matter of the surgeon's judgment. The role of proximal parent vessel ligation must also be considered in the decision-making process regarding the treatment of giant or technically difficult aneurysms (114). Further refinements in cerebral monitoring that can accurately reflect intracellular processes in all territories affected by the application of temporary clips or balloon occlusion and development of more effective forms of cerebral protection may permit safer use of this technique. An adequately controlled clinical trial of temporary occlusion with or without putative "cerebral protection" is needed to confirm the efficacy of this technique.