Histone deacetylase inhibitors in oral squamous cell carcinoma treatment.

Introduction: The involvement of the histone deacetylases (HDACs) family in tumor development and progression is well demonstrated. HDAC inhibitors (HDACis) constitute a novel, heterogeneous family of highly selective anticancer agents that inhibit HDACs and present significant antitumor activity in several human malignancies, including oral squamous cell carcinoma (OSCC). Areas covered: This review summarizes the current research on the anticancer activity of HDACis against OSCC. The review also presents the molecular mechanisms of HDACis action and the existing studies evaluating their utilization in combined therapies of OSCC. Expert opinion: The currently available data support evidence that HDACis may provide new therapeutic options against OSCC, decreasing treatment side effects and allowing a more conservative therapeutic approach. Future research should be focused on in vivo and clinical evaluation of their utilization as combined therapies or monotherapies. Before HDACis can be brought into clinical practice as treatment options for OSCC, further evaluation is needed to determine their optimal dosage, the appropriate duration of treatment and whether they should be used in combination or as stand-alone therapeutics.

Bilateral aberrant origin of the inferior thyroid artery from the common carotid artery.

The thyroid gland is mainly supplied by the superior and inferior thyroid arteries, with the latter being its principal arterial supply in adults. The inferior thyroid artery usually arises from the thyrocervical trunk, and less frequently from the subclavian artery. Rarely, it may originate from the vertebral artery or the common carotid artery. In the present report, we describe a unique case of a 56-year-old patient, undergoing total thyroidectomy and level VI lymph node dissection for papillary thyroid carcinoma, with aberrant origin of both inferior thyroid arteries from the common carotid arteries.

Nasal polyps: heredity, allergies, and environmental and occupational exposure.

OBJECTIVE: To determine the role of heredity, allergies, smoking, and environmental and occupational exposure in the epidemiology of nasal polyposis. STUDY DESIGN: A case-control study comprising 100 patients with nasal polyps admitted to three Athens hospitals and 102 controls from the general population. Gender, educational level, family history, allergies, smoking, occupational activities, and environmental exposure were examined as eventual determinants. The prevalence of each determinant was compared between cases and controls using multiple logistic regression, and odds ratios (ORs) were estimated. RESULTS: A total of 13.3% of the patients and none of the controls had a history of polyps in the family. According to multiple logistic regression, the OR for certain allergies was 19.1 and for probable allergy was 9.0, with the prevalence among patients being 64% and 12%, respectively. The OR for certain environmental exposures was 15.0 and for occupational exposures was 21.4. Occupational exposure to chemicals was a predominant factor among patients. No significant difference was found between nasal polyps and educational level or smoking habits. CONCLUSIONS: The development of nasal polyps seems to be strongly related to family history and a history of allergies, but the role of smoking remains controversial. Occupational and environmental exposures probably enhance the appearance of the disease on the basis of genetic predisposition.

Radiologic evaluation of the ear anatomy in pediatric cholesteatoma.

The aim of the study was to describe computed tomography (CT) findings in middle ear cholesteatoma in pediatric patients. A cohort of 32 children with cholesteatoma (3-14 years old) entered the study. From them, 30 presented acquired cholesteatoma (AC), and 2 presented congenital cholesteatoma. All of the children were investigated using CT before surgery of the middle ear and mastoid. Computed tomography was performed with 1- or 2-mm axial and coronal sections of both temporal bones. Nineteen children with AC (63.3%) revealed a diffuse soft-tissue density isodense with muscle, whereas in 6 of them, the mass mimicked inflammation. The remaining revealed localized soft-tissue mass with partially lobulated contour. In AC, ossicular erosion was detected in 23 cases (76.7%), abnormal pneumatization in 19 cases (63.3%), and erosion-blunting of spur and enlargement of middle ear or mastoid in 8 cases (26.7%). The 2 congenital cholesteatomas revealed soft-tissue mass with polypoid densities, while a semicircular canal fistula was detected in one of them. High-resolution CT facilitates early diagnosis and appropriate treatment of pediatric cholesteatoma by assessing the anatomic abnormalities and the extent of disease, which are crucial in middle ear and mastoid surgery.

Association between nursing workload and mortality of intensive care unit patients.

PURPOSE: To investigate differences in mortality of intensive care unit (ICU) patients according to the ratio between total patient care demands and nurse staffing. DESIGN: Observational, prospective study. Patients consecutively admitted in the medical-surgical ICU of a Greek hospital over a 1-year period were enrolled. METHODS: The Therapeutic Intervention Scoring System (TISS)-28 was used for measuring patient care demands. Daily sum of TISS-28 of patients and daily number of nurses were considered for estimating median and peak patient exposure to nursing workload. According to the values of median and peak patient exposure to nursing workload, patients were divided into three groups (low, medium, and high). Logistic regression was used for evaluating the associations between mortality during ICU length of stay and median or peak patient exposure to nursing workload, after adjusting for patient clinical severity. FINDINGS: 396 patients were included and 102 died. Differences in ICU mortality between high and low groups of median and peak patient exposure to nursing workload, although not statistically significant, were clinically remarkable, both when all patients were studied and when medical and surgical patients were separately studied. CONCLUSIONS: Consideration of individual differences in patient acuity might add sensitivity to the detection of associations between nurse understaffing and ICU mortality. CLINICAL RELEVANCE: The findings indicate that not only differences among nurse characteristics, but also differences in patient care demands, are important when investigating the effect of nurse understaffing on mortality of ICU patients. Proper nurse staffing levels should be based on the estimation of total patient acuity, rather than on the absolute number of patients.

Nursing workload associated with fever in the general intensive care unit.

BACKGROUND: Fever in a patient in the intensive care unit necessitates several nursing tasks. Moreover, factors associated with increased patient care needs may be associated with fever. OBJECTIVE: To identify relationships between fever and characteristics of fever and nursing workload at the patient level. METHODS: A prospective study was conducted in a medical-surgical intensive care unit. The sample consisted of 361 patients consecutively admitted from October 2005 to August 2006. Each patient's body temperature was measured by using a tympanic membrane or an axillary thermometer. The Therapeutic Intervention Scoring System-28 was used to measure nursing workload. RESULTS: A total of 188 patients (52.1%) had fever. Mean daily scores on the Therapeutic Intervention Scoring System and on 5 of its 7 categories were significantly higher for febrile patients than for nonfebrile patients. Fever was an independent predictor of the mean daily scores for all patients (P < .001). Peak body temperature but not duration of fever also was an independent predictor of mean daily scores for febrile patients (P < .001). CONCLUSION: In a general intensive care unit, fever in patients should be taken into consideration for the proper allocation of nursing personnel.

Temporal bone and mastoid process morphology in Mediterranean population.

The mastoid process originates from a recent phylogenetic formation and is currently considered as an evolution of the supper-structures bones. The aim of this study was the detailed description of the anatomic elements of the mastoid and the temporal bone in a large Greek adult corpse material. In total, 298 temporal bones from 149 cadaverous (74 male and 75 female) were examined from 1973 through 1993. Concerning the shape of the mastoid apex 94.0% were normal, while the rest presented several variations No statistically significant difference was revealed between genders. The diameters and axis of the temporal bone presented an independent correlation with gender in a multiple regression model. This prescription may add in easier surgical approach by adding new morphological details directly from the corpse material.

The culture site of the gallbladder affects recovery of bacteria in symptomatic cholelithiasis.

AIM: Traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis. AIM: to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture. METHODS: A cohort of 137 patients with symptomatic cholelithiasis was enrolled. After surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. Identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. Wilcoxon's paired and Chi-square tests were used for comparison between continuous and discrete parameters, respectively. RESULTS: Thirty-one patients (22.6%) demonstrated at least one positive culture sample. Positivity was 31/31 (100.0%) in neck samples, 20/31 (64.5%) in body and 13/31 (41.9%) in fundus samples (P<0.001). The microorganisms identified were Escherichia coli (14 cases) and Enterococcus faecalis (10 cases), followed by Staphylococcus aureus (3 cases), Pseudomonas aeruginosa, Enterococcus faecium, Enterobacter aerogenes and Enterobacter cloacae (1 case each). Mean bacterial concentrations in positive samples derived from the neck (272.2 +/- 187.5) were higher (P<0.01) when compared to those derived from both the body (38.2 +/- 28.7) and the fundus (12.5 +/- 11.3). Mean bacterial concentrations in positive samples derived from the body were higher (P<0.01) than those derived from the fundus. CONCLUSION: The neck of the gallbladder hosts the biggest bacterial load in comparison with the body and the fundus. This difference might be attributed to the presence of Rokitansky-Aschoff sinuses, which is the main histological characteristic of the region.

Cross-transmission of multidrug-resistant Acinetobacter baumannii clonal strains causing episodes of sepsis in a trauma intensive care unit.

OBJECTIVE: To investigate the mode of transmission of imipenem-resistant Acinetobacter baumannii strains causing episodes of sepsis. SETTING: A 7-bed trauma intensive care unit (ICU) in an orthopedic hospital in Greece. DESIGN: During a 14-week period (from January 10 to April 16, 2006), clinical specimens, along with samples taken on a weekly basis from the ICU environment and from the hands of health care workers (HCWs), were prospectively tested for imipenem-resistant A. baumannii. Pulsed-field gel electrophoresis was used to study the genetic relatedness of the isolates recovered from these specimens and samples. RESULTS: During the survey, imipenem-resistant A. baumannii was identified in 14 hospitalized patients, from whom 40 multidrug-resistant and imipenem-resistant A. baumanii isolates were recovered. These pathogens caused episodes of bacteremia and sepsis in all but one of the patients and contributed to the death of 3 patients. Samples for culture were obtained from the environment and from the hands of HCWs; 29 imipenem-resistant A. baumannii isolates were recovered from the environment, and 12 from HCWs. One predominant genotype and 2 less predominant genotypes were detected among the 81 imipenem-resistant A. baumannii isolates. All 3 of these genotypes were found among patients and HCWs and were recovered from environmental samples. INTERVENTIONS: Control measures consisted of the closure of the ICU and the transfer of the patients to other units. The ICU was disinfected, and adherence to proper hand hygiene protocol was reinforced. These same clonal isolates were not recovered from clinical or environmental samples during the month after the reopening of the ICU. CONCLUSIONS: The extensive dissemination of imipenem-resistant A. baumannii clonal strains causing episodes of bacteremia and/or sepsis resulted from modes of transmission via multiple contaminated surfaces and objects and transiently colonized HCWs' hands. Closure of the ICU and its meticulous environmental decontamination led to the successful control of the outbreak.

Patient severity as an indicator of nursing workload in the intensive care unit.

The importance of measuring nursing workload in the intensive care unit (ICU) has been supported by both an increasing demand for nursing personnel and the relationship of nursing workload with patient safety. According to previous studies, the correlation between clinical severity of ICU patients and nursing workload measured by Therapeutic Intervention Scoring System has been estimated to be particularly high. The aim of this study was to investigate whether clinical severity of ICU patients can be used for the prediction of nursing workload on a daily basis. All patients admitted in the ICU of the General University Hospital of Patras for a 5-month period were enrolled in the study. Projet de Recherche en Nursing (PRN) Réa and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of patients were calculated, the first on a daily basis and the second on the day of admission. Simple linear regression was used for statistical analysis of data. One hundred thirty-eight patients were studied. A progressive increase in mean daily PRN Réa of patients all along the amplitude of APACHE II values was shown. APACHE II could predict 25.6% (p < 0.01) of the daily variability of PRN Réa of patients. Regarding categories of PRN Réa, respiration, communication, diagnostic methods and treatments were significantly predicted by APACHE II. APACHE II explained higher proportions of PRN Réa in medical male patients aged >60 years. Clinical severity of the ICU patients measured by APACHE II is an important early indicator of daily nursing workload, especially of care demands associated with respiration, diagnostic methods and treatments.

Anatomical landmarks: dimensions of the mastoid air cell system in the Mediterranean population. Our experience from the anatomy of 298 temporal bones.

The mastoid apophysis originates from a recent phylogenetic formation, associated with the standing attitude and it is currently considered as an evolution of the bone super-structures. The aim of the present study was to measure the diameters of the mastoid and the temporal bone in the Greek adult population. A total of 298 temporal bones from 149 cadavers (74 male, 75 female) were examined. The distances between six landmarks were measured by means of a pachymeter on both vertical and transverse axes of the mastoids and the temporal bone. The estimated mean values for each dimension were as follows: vertical diameter, 2.37 +/- 0.42 cm; transverse diameter, 2.33 +/- 0.51 cm; anterior margin, 2.12 +/- 0.67 cm; posterior margin, 1.96 +/- 0.55 cm; oblong diameter, 10.30 +/- 0.60 cm; while the mean distance between the mastoid apex and mandibular fossa calva was 3.67 +/- 0.35 cm. Gender differences were detected for the vertical (P < 0.001), the transverse diameter of the mastoid (P < 0.001), the anterior (P < 0.001) and the posterior margin of the mastoid (P < 0.001). In both genders, the vertical diameter of the mastoid was positively correlated with the transverse diameter, as well as with its anterior and posterior margins. In the present study, direct measurements of the mastoid and temporal bone in a Mediterranean population are reported. This description may facilitate a more accurate surgical approach to the temporal bone structures.

Nitric oxide, antioxidant capacity, nitric oxide synthase and xanthine oxidase plasma levels in a cohort of burn patients.

BACKGROUND: Nitric oxide (NO) is an important signal molecule in many types of cells and tissues. Efficiently balanced NO production was noted to play an important role in the healing of burns. However, the exact pathophysiological role of NO in burns and its potent relation with clinical and laboratory parameters has not been elucidated. METHODS: A cohort of 23 burn patients followed for 5 days were enrolled. NO, antioxidant capacity (AC), NO synthase (NOS) activity and xanthine oxidase (XO) activity were indirectly determined by fluorophotometer. Multiple regression against total burn surface area (TBSA), age, weight, height, proximity of septic episode, hemoglobin, white blood cells, percent of neutrophils, platelets, glucose, urea, potassium, sodium and albumin was performed. RESULTS: Elevation of NO, XO and AC levels is observed from day 2 (p<0.00001), day 4 (p=0.005) and day 6 (p=0.036), respectively. At the end of follow-up period (day 6), NO production was found to independently correlate with TBSA, glucose levels and percent of neutrophils (p=0.0004), AC with age, hemoglobin and glucose levels (p=0.012), and NOS with proximity of septic episode and glucose levels (p=0.027). CONCLUSIONS: NO production exerts its prophylactic effect from the first 24h after burn, and is independently correlated with severe injury, enhanced neutrophil motivation and augmented glucose levels, thus possibly representing a response to stress. This need might trigger induction of XO and salvage of antioxidants, as suggested by their rise at a later stage. These data underline that an effort to compromise stress and to administer antioxidants could be a priority in the treatment of these patients.

Haemostasis impairment in patients with obstructive jaundice.

As part of the multifactorial role of liver in protein synthesis, many coagulation factors, natural anticoagulants, and compounds of the fibrinolytic system are produced in the liver. A prolonged liver disease, either biliary obstruction or parenchymal liver disease, is consecutively accompanied by abnormal clotting. In the present paper we review the haemostasis impairment in obstructive jaundice with special reference to the hepatic cirrhosis and failure, to systemic inflammation and sepsis that develops in cholestatic diseases, and finally in some other benign or malignant diseases including pancreatic adenocarcinoma, acute pancreatitis, cholangiocarcinoma, and hepatocellular carcinoma. Finally, a special reference to the possible therapeutic interventions has been made. The aim of the present review is to collect the current concepts concerning the haemostasis impairment in obstructive jaundice and provide practical guidelines for the diagnostic and therapeutic strategies. Understanding the pathophysiology of haemostatic changes in patients with cholestasis, and, more generally, liver disease, is the hallmark of accurate diagnosis and treatment.

Fever and standard monitoring parameters of ICU patients: a descriptive study.

OBJECTIVE: To investigate the effect of fever episodes and fever characteristics on heart rate, arterial blood pressure and arterial oxygen saturation of intensive care unit (ICU) patients. METHODS: This was a prospective study conducted in the medical-surgical ICU of General University Hospital of Patras, Greece. All patients who were consecutively admitted from October 2005 to February 2006 and manifested fever during ICU stay were enrolled. A tympanic membrane or an axillary thermometer was used for the measurement of patient temperature. Standard monitoring parameters were recorded by nursing personnel at 1-h intervals. RESULTS: Seventy-five ICU patients manifested fever during the study period. Increase of core temperature during fever episodes was followed by a significant increase in heart rate (p<0.001) and decreases in arterial blood pressure (p<0.001) and arterial oxygen saturation (p=0.002). Alterations of heart rate and arterial blood pressure were significantly affected by magnitude of fever, while alteration of arterial oxygen saturation was affected by etiology of fever. CONCLUSIONS: The present findings confirmed the effect of fever episodes on standard monitoring parameters of ICU patients. However, alterations of these parameters, although statistically significant, were not clinically important and cannot guide antipyretic treatment.

Tissue concentration of transforming growth factor beta1 and basic fibroblast growth factor in skin wounds created with a CO2 laser and scalpel: a comparative experimental study, using an animal model of skin resurfacing.

Although a number of ablative-laser techniques based on CO(2) and Er: YAG laser devices have been successfully developed and used in the clinical setting, the bio-molecular processes influencing wound healing after exposure to laser energy are not well elucidated. In this study, we aim to assess the impact of the mechanism of injury on the secretion of transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) in various stages of wound healing, in wounds created with a CO(2) laser and scalpel. Ten Wistar rats were used to determine the levels of growth factor proteins TGF-beta1 and bFGF after CO(2) laser- and scalpel-induced skin injury. Tissue was excised on day 0 for untreated skin (control sites), and on days 1, 10, 30, and 90 following laser and scalpel surgery. Specimens were processed for histopathological analysis and for determining the concentration of growth factors by a Western blot technique. The concentration of TGF-beta1 increased markedly, at day 1 postinjury, from a baseline of 130+/-16 mm(2) (mean surface area of blotted-protein lanes) to 261+/-23 mm(2) and 394+/-22 mm(2) for laser-inflicted injury and scalpel wounds, respectively; the latter values were found to differ significantly (p<0.001). The concentration of b-FGF on day 10 postinjury differed significantly (p<0.001) between the laser sites (553+/-45 mm(2)) and the corresponding scalpel sites (418+/-41 mm(2)). Laser energy alters local tissue secretion of TGF-beta1 and bFGF of skin injuries created with the CO(2) laser compared with wounds created with a scalpel. These differences might have an impact on various aspects of wound healing of skin injuries created by a laser.

In vivo effect of carbon dioxide laser-skin resurfacing and mechanical abrasion on the skin's microbial flora in an animal model.

BACKGROUND: Although beam-scanning carbon dioxide (CO2) lasers have provided a highly efficient tool for esthetic skin rejuvenation there has been no comprehensive animal studies looking into microbial skin changes following CO2 laser skin resurfacing. OBJECTIVE: To evaluate the in vivo effects of CO2 laser skin resurfacing in an experimental rat model in comparison with mechanical abrasion on the skin microbial flora. METHODS: Four separate cutaneous sections of the right dorsal surface of 10 Wistar rats were treated with a CO2 laser, operating at 18 W and delivering a radiant energy of 5.76 J/cm2, while mechanical abrasions of the skin were created on four sections of the left dorsal surface using a scalpel. Samples for culture and biopsies were obtained from the skin surfaces of the rats on day 1 of application of the CO2 laser or mechanical abrasion, as well as 10, 30, and 90 days after the procedure. The presence of four microorganisms (staphylococci, streptococci, diphtheroids, and yeasts) was evaluated as a microbe index for the skin flora, and colony counts were obtained using standard microbiological methods. RESULTS: Skin biopsy specimens, following CO2 laser treatment, initially showed epidermal and papillary dermal necrosis and later a re-epithelization of the epidermis as well as the generation of new collagen on the upper papillary dermis. The reduction in microbial counts on day 1 of the CO2 laser-inflicted wound was statistically significant for staphylococci and diphtheroids compared with the baseline counts (p=.004 and p<.001, respectively), and for staphylococci, diphtheroids, and yeasts compared with the scalpel-inflicted wound on the same day (p=0.029, p<.001, and p=.030, respectively). CONCLUSIONS: Skin resurfacing using CO2 lasers considerably reduces microbial counts of most microorganisms in comparison with either normal skin flora or a scalpel-inflicted wound. This might contribute to the positive clinical outcome of laser skin resurfacing.

CTX-M-1 extended-spectrum beta-lactamase-producing Proteus mirabilis in Greece.

To examine the dissemination of CTX-M-type extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Proteus mirabilis, 91 nonrepetitive ESBL-producing P. mirabilis were collected from infected patients in a tertiary Greek hospital during September, 2001, to May, 2004. A bla (CTX-M) gene was amplified in one isolate (strain A328), but bla (CTX-M) was not detected in any of the remaining ESBL producers. Sequencing results showed that P. mirabilis A328 produced a CTX-M-1 enzyme while PCR mapping of the genetic element carrying bla (CTX-M-1) revealed that the gene was located downstream of an ISEcp1B element. The cefotaxime resistance determinant was easily transferable and carried on a 70-kb plasmid. The emergence of CTX-M-1- producing P. mirabilis indicates the need for early recognition of such strains to be able to control their spread in our hospital and community environment.

A fatal case of Ludwig's angina and mediastinitis caused by an unusual microorganism, Gemella morbillorum.

We present a case of Ludwig's angina in a 48-y-old immunocompetent male caused by an unusual pathogen, Gemella morbillorum. The infection was complicated with mediastinitis and despite aggressive management of the disease the patient died after 12 d of hospitalization. This is the first reported case of Ludwig's angina caused by G. morbillorum and emphasizes that the disease remains a potentially lethal infection.

Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy.

AIMS/BACKGROUND: Hepatic stimulator substance (HSS) is a liver-specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats. METHODS: Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA. RESULTS: Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA-intoxicated and HSS-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, HSS ameliorated liver regenerative indices--DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity--in a statistically significant manner. CONCLUSIONS: Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.