Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas.

OBJECTIVE: To investigate the clinical significance of vimentin expression at early and late events of tobacco/areca nut-associated oral tumorigenesis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was carried out on paraffin-embedded tissues of oral mucosa normal (n = 10), inflammatory lesions (n = 19), leukoplakia (n = 52), submucous fibrosis (n = 71) and tumours/cut margins (n = 227 each), using anti-vimentin antibody, and the expression profile was correlated with patients' clinical parameters. Immunofluorescence, Western blot and RT-PCR analysis were also carried out wherever adequate and fresh tissues were available. RESULTS: Aberrant vimentin expression was seen in hyperplastic, dysplastic and fibrotic tissues, which showed statistically significant correlation with the histopathological grade of dysplasia (P = 0.001) and fibrosis (P = 0.009). Vimentin expression also showed statistically significant correlation with tumour size (P = 0.048), clinical stage (P = 0.013), regional lymph node metastases (P = 0.001), local recurrence (P = 0.001) and survival (P = 0.021) of patients with oral squamous cell carcinoma (OSCC). Its expression in invasive fronts statistically correlated with development of nodal metastasis and local recurrence. CONCLUSIONS: Our results suggest possible role of vimentin in early events of tobacco/areca nut-associated oral tumorigenesis, which may prove useful to predict the malignant potential of high-risk oral lesions. Further, association between vimentin expression in invasive fronts and aggressive phenotype of tumours may help clinicians to choose the appropriate treatment modality for OSCC management.

Translational barriers and opportunities for emergency preservation and resuscitation in severe injuries.

BACKGROUND: Hypothermia is commonly used for organ and tissue preservation in multiple clinical settings, but its role in the management of injured patients remains controversial. There is no doubt that temperature modulation is a powerful tool, and hypothermia has been shown to protect cells during ischaemia and reperfusion, decrease organ damage and improve survival. Yet hypothermia is a double-edged sword: unless carefully managed, its induction can be associated with a number of complications. METHODS: A literature review was performed to include important papers that address the impact of hypothermia on key biological processes, and explore the potential therapeutic role of hypothermia in trauma/haemorrhage models. RESULTS: No clinical studies have been conducted to test the therapeutic benefits of hypothermia in injured patients. However, numerous well designed animal studies support this concept. Despite excellent preclinical data, there are several potential barriers to translating hypothermia into clinical practice. CONCLUSION: Therapeutic hypothermia is a promising life-saving strategy. Appropriate patient selection requires a thorough understanding of how temperature modulation affects various biological mechanisms.

Molecular identification, characterization, and antagonistic activity profiling of Bacillus cereus LOCK 1002 along with the in-silico analysis of its presumptive bacteriocins.

Objectives: This research aimed to isolate, identify, and characterize a new strain of Bacillus cereus through different molecular biology approaches so that it could be further studied for therapeutic purposes against selective enteric pathogens. Materials and Methods: Pure isolates of B. cereus were prepared from buffalo yogurt samples in REMBA medium. Initially, the morphological, physiological, and biochemical properties were studied accordingly. Following the tests, the molecular identification for the strain identification was conducted through plasmid DNA extraction, PCR, agarose gel electrophoresis, and 16S rRNA sequencing up to 1.37 kb. Afterward, the antibiotic sensitivity [Epsilometer test (E-Test)] and antifungal activity were tested considering different concentrations. Being classified from the aforementioned tests, a comprehensive antimicrobial activity test was conducted using the cell-free-supernatant (CFS) of the test strain against selective enteric pathogens in humans in vitro. Besides, the different clusters of genes were identified and characterized for understanding the presumptive bacteriocins present in the CFS of the strain in silico, where molecular string properties were calculated. Finally, the evolutionary relationship among diversified bacteriocins synthesized by different Bacillus strains was studied to predict the CFS-containing bacteriocins of the new strain. Results: Purified isolates of B. cereus were Gram-positive rods and showed significant tolerance (p < 0.0001) to different concentrations of pH, phenol, bile salt, and NaCl. 16S rRNA revealed the strain as LOCK 1002, which was strongly sensitive to all the antibiotics used and resistant to selective antifungal agents. The CFS of B. cereus LOCK 1002 was found to be a very promising antagonist to all the enteric pathogens used in the culture condition. Two gene clusters were predicted to be interconnected and responsible for different presumptive bacteriocins. Conclusion: The newly identified LOCK 1002 can be a very potent strain of B. cereus in use as an antimicrobial agent for having different bacteriocin coding gene clusters.

Characteristics of infertile couples.

The objective of the study was to evaluate the sociodemographic characteristics and to find out the causes of infertility among the couple attending out patient department of infertility unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) from January to December 2007. This is a descriptive observational study. Data were analyzed done manually and statistical analysis was calculated by Statistical package for social sciences (SPSS) program. During this period 3184 patients were attended out patient department (OPD) of infertility unit (IU-I & II). Among them primary infertility was present in 1971(61.90%) and secondary infertility in 1213(38%) cases. One thousand four hundred and two (1402) patient's complete data were reviewed from OPD register book of IU-I. The mean duration of the infertility was 4.7(4.52) years. The mean age of female patient was 26.5±5.35 years. The mean age of male patient was 34.56±6.33 years. A positive male factor problem alone was found in 13% couples, female factors in 71.46% couples and unexplained infertility in 15.47% couples. Among the male factor Oligozoospermia (33.33%) was the most common cause of male infertility. Anovulation (52.16%) was the most common cause of female infertility and major cause of anovulation was Polycystic ovary syndrome (PCOS) (29.90%). Fibroid uterus, Bilateral tubal block and Pelvic inflammatory disease (PID) were significantly (p<0.001) higher in secondary infertility. Endometriosis and unexplained infertility were significantly (p<0.001) higher in primary infertility. Distribution of other causes of infertility was same for both primary and secondary infertility.

Status of HIV infection among the pregnant women attending in outpatient department.

Human immunodeficiency virus (HIV) infection has been spreading rapidly in the developing countries and vertical transmission also taking place. This study has been done to find out the prevalence of HIV infection among the pregnant women, so that necessity of routine screening test can be identified. It is a cross sectional study. Five hundred two pregnant women were included. Three ml venous blood was taken and then HIV screening test was done by ELISA method. All reactive tests were confirmed by Western blot antibody testing. The positive cases were followed up and necessary treatment was given. Delivery was conducted in this hospital. Baby's blood was tested to see vertical transmission after 18 months. Most of the subject were educated housewife, mean age was 25 years. Six (6%) husband was overseas service holder, 12% were smoker and 1.6% had drug addiction. Eight (8%) subject had previous history of blood transfusion and 49% subject or her husband had history of surgery or got parental therapy. 2% subject gave the history of familial disharmony and 2% had multiple sex partners. HIV infection was found in 2 patients (0.4%). Both of them got infection from their husband. One husband was over seas service holder and another one was injecting drug user. For the prevention of spread, reduction of vertical transmission and providing early management to the positive patient all pregnant women should be screened for HIV routinely.

Ethical awareness in surgical management.

Getting information about disease has been suffering, the management needed, procedure and complication of that management, is the right of the patients. Giving that information to the patients is the responsibility of the physician/surgeons. The objective of this study was to assess the existing awareness of the surgeons and female patients regarding ethical issues of medical practices. This observational study was undertaken in the gynecological department of two tertiary hospital of the capital city of Bangladesh. One hundred fifty five patients were interviewed who were underwent surgical management for different gynecological problems. Mean age of the studied population was 41 (SD+/-10) years. All of them were from lower and lower middle economical classes. Sixty three percents (63%) were illiterate. Consent for the surgery was given by the husband in 52% cases, by son in 22% cases, by herself in 1% case and remaining by other relatives. About 50% of the patients did not know the name of their disease, 75% of them never talked with the surgeon. Only in 31% cases surgeon spontaneously explained them about her disease. Most of them had no knowledge about anaesthesia, operating time, need of blood transfusion, operating complications and long-term effects of the surgery they had. The result of this study showed very poor awareness about medical ethics and patient's right.

[The war on (too many) fluids. New horizons in combat medicine]. / Krieg und Flüssigkeitsmanagement. Neue Horizonte.

In the coming years, our approach to the bleeding patient will have to change radically. The inevitable knowledge from the wars in Iraq and Afghanistan permits the prediction that conventional crystalloids will sooner or later disappear from volume replacement therapy. The dogma that fluids must always be given will be abandoned, to be replaced by the practice of careful and goal-directed resuscitation. In the near future, we would rely on designer fluids and sophisticated pharmacological agents to deliver personalized resuscitation based upon the specific needs of the individual patient.

An update on fluid resuscitation.

Hemorrhagic shock is the leading cause of death in civilian and military trauma. Effective hemorrhage control and better resuscitation strategies have the potential of saving lives. However, if not performed properly, resuscitation can actually exacerbate cellular injury caused by hemorrhagic shock, and the type of fluid used for resuscitation plays an important role in this injury pattern. It is logical to prevent this cellular injury through wiser resuscitation strategies than attempting immunomodulation after the damage has already occurred. It is important to recognize that unlike numerous other variables, resuscitation is completely under our control. We decide who, when and how should get resuscitated. This paper summarizes data from a number of studies to illustrate the differential effects of commonly used resuscitation fluids on cellular injury, and how these relate to clinical practice. In addition, some novel resuscitation strategies are described that may become clinically available in the near future.

Design of preservation solutions for universal tissue preservation in vivo: demonstration of efficacy in preclinical models of profound hypothermic cardiac arrest.

The design of new solutions for the universal preservation of tissues is a quest that would facilitate multiple-organ harvesting from organ donors since current preservation solutions do not provide optimum preservation for all organs. In contrast, a new approach to bloodless surgery using hypothermic blood substitution (HBS) to protect the whole body during profound hypothermic circulatory arrest (clinical suspended animation) has focused on the development of a hybrid solution design with the objective of providing universal tissue preservation. In this study, a porcine model of uncontrolled lethal hemorrhage was employed. A combination of two new solutions, maintenance and purge, was used in a cardiopulmonary bypass (CPB) technique to affect profound hypothermia and prolonged cardiac arrest (60 min), with resuscitation after surgical repair of the vascular deficit induced to affect exsanguination. After rewarming and recovery, pigs were monitored for 6 weeks for neurological deficits, cognitive function (learning new skills), and organ dysfunction. All the normothermic control animals died (n = 10), whereas 90% (9 of 10) in the HBS group survived (P < .05). Moreover, all of the survivors were neurologically intact, displayed normal learning and memory capability, and had no long-term organ dysfunction. Histology of brains after 6 weeks revealed no ischemic damage in marked contrast to control animals, which all showed diffuse ischemic damage. The demonstrated efficacy of these synthetic, acellular HBS solutions for protection of all the tissues in the body during clinical suspended animation justifies their consideration for multiple-organ harvesting from cadaveric and living donors.

Magneto-structural coupling in [Formula: see text].

[Formula: see text] compound is well Known to show the frustration of the spin structure. At 12 K, [Formula: see text] distorts to break symmetry of the degenerated frustrated spin states by the spin-Peierls-like phase transition, accompanying with the antiferromagnetic ordering. On the other hand, [Formula: see text] undergoes a Jahn-Teller phase transition at a temperature of 310 K, differing from the low temperature ferrimagnetic transition temperature [Formula: see text] of about 60 K. It is also reported that [Formula: see text] shows another magnetic phase transition at about 30 K. These two phase transitions accompanying with the lattice change can be understood by the magneto-elastic interactions. Two interactions, the Jahn-Teller interaction and the spin-Peierls-like interaction are co-exist in [Formula: see text] system. In this report the [Formula: see text] compounds with x = 0.8, 0.6 and 1 are investigated by the X-ray diffraction measurements. From these measurements the crystal structures are determined. The full width at half maximum and integrated intensity give the fruitful information for magnetic elastic interactions.

Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model.

BACKGROUND: Seven isoforms of histone deacetylase Class III have been reported - Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1, reduces mortality in a mouse model of lethal-cecal-ligationand- puncture (CLP)-induced septic shock. Our present study was aimed at determining whether selective inhibition of SIRT2, with AGK2, would decrease animal death and attenuate the inflammatory response in a septic model. METHODS: Experiment I: C57BL/6J mice were intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2 h later subjected to CLP. Survival was monitored for 240 hours. Experiment II: mice treated the same way as Experiment I, were grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritoneal fluid and peripheral blood were examined at 24 and 48 hours for cytokine production. Samples of blood at 48 h were also allocated to assess coagulability using Thrombelastography (TEG). Morphological changes of bone marrow were evaluated from long bones (femurs and tibias) with hematoxylin and eosin (H&E) staining. Bone marrow atrophy was quantified by a blinded pathologist. Experiment III: cytokines in supernatant of the cultured normal primary splenocytes were measured after the cells were stimulated by lipopolysaccharide and treated with or without AGK2 (10 µM) for 6 hours. RESULTS: AGK2 significantly reduced mortality and decreased levels of cytokines in blood (TNF-α: 298.3±24.6 vs 26.8±2.8 pg/ml, p=0.0034; IL-6: 633.4±82.8 vs 232.6±133.0 pg/ml, p=0.0344) and peritoneal fluid (IL-6: 704.8±67.7 vs 391.4±98.5 pg/ml, p=0.033) compared to vehicle control. Also, AGK2 suppressed the TNF-α and IL-6 production in the cultured splenocytes (TNF-α: 68.1±6.4 vs 23.9±2.8 pg/ml, p=0.0009; IL-6: 73.1±4.2 vs 49.6±3.0 pg/ml; p=0.0051). The TEG data showed that the mice subjected to CLP displayed prolonged fibrin formation and fibrin cross-linkage time, slower clot formation, decreased platelet function, and clot rigidity. AGK2 treatment was associated with dramatic improvements in fibrin cross-linkage and clot formation times, without a significant impact on the clot initiation parameters or platelet function. Additionally, AGK2 significantly attenuated the bone marrow atrophy (58.3±6.5 vs 30.0±8.2%, p=0.0262). CONCLUSION: Selective inhibition of SIRT2 significantly improves survival, and attenuates sepsis-associated "cytokine storm", coagulopathy, and bone marrow atrophy in a mouse model of lethal septic shock.

A five-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding.

A 5-year prospective study of 4,934 children of different ethnic groups has demonstrated a 3-fold increase of postneonatal mortality and childhood morbidity in the offspring of consanguineous Pakistani parents. Most of these families contained more than one consanguineous union, resulting in a mean inbreeding coefficient for their children of 0.0686. It is estimated that 60% of the mortality and severe morbidity of this group of children could be eliminated if inbreeding ceased. However consanguinity is much favoured in this minority group, and health education will have to be carefully and sensitively handled.

Saphenous vein graft infection: a fatal complication of postoperative mediastinitis.

Infection and erosion of the saphenous vein graft with mediastinal hemorrhage is a rare but highly lethal complication of cardiac surgery. This is associated with a mortality rate of 50%. We present a patient who died during the postoperative period due to this complication.

Can pleural effusions cause cardiac tamponade?

Pleural effusion(s) can increase the pressure of an otherwise insignificant pericardial effusion to a degree that can result in cardiac tamponade. The case histories presented here illustrate the importance of recognizing this phenomenon and altering our treatment algorithm to drain the pleural effusions instead of the pericardial collections.

A placental-derived tissue matrix as a bowel wall substitute in rats: preliminary study.

BACKGROUND: Occasionally, conventional closure of an intestinal wall defect (fistula) is not possible. The development of a biologic material that can be used in this setting would solve a significant clinical problem. We hypothesized that a collagen patch (connective tissue matrix [CTM]) designed to allow tissue regeneration was such a material. METHODS: To test this hypothesis, we performed a laparotomy on 75 male Sprague-Dawley rats (experiment A) and removed 25% of the anterior cecal wall (1 cm in diameter) to compare intestinal wound healing in four situations: (1) control (no repair), (2) fibrin glue repair, (3) primary repair, and (4) repair with CTM (human placental bilayer, types I, III, and IV). Animals were killed at 1, 2, 4, and 6 weeks. Healing was graded by bursting pressure expressed in millimeters of mercury, histologic score (0 to 4), and mortality rates. After this, we used the same protocol to remove 80% of the cecal wall (1.5 x 2.0 cm) in 19 animals (experiment B) to compare (5) fibrin glue repair alone with (6) CTM repair in a situation in which the defect was too large for primary repair. RESULTS: CTM repair of a lethal cecal wall defect (experiment A) is equivalent to either primary repair or fibrin glue repair. When the defect is too large for primary repair (experiment B), repair with fibrin glue also does not work. However, in this same setting, CTM repair is successful (p < 0.00001). CONCLUSIONS: Intestinal wall defects not suitable for conventional closure can be repaired successfully with a collagen patch, with histologic characteristics similar to those seen with primary repair.

Resuscitation-induced pulmonary apoptosis and intracellular adhesion molecule-1 expression in rats are attenuated by the use of Ketone Ringer's solution.

BACKGROUND: Resuscitation with Lactated Ringer's solution after hemorrhagic shock in rats has been shown to cause early cellular injury in the lung. We hypothesized that the use of energy substrates, such as ketone bodies, in the resuscitation fluids would protect against this injury. As markers of cellular injury we measured the induction of apoptotic cell death and the expression of Intracellular Adhesion Molecule-1 (ICAM-1). STUDY DESIGN: Male Sprague Dawley rats (n = 35) under inhaled isoflurane anesthesia had placement of femoral arterial and venous catheters. A three-stage hemorrhage model was used for this experiment. There was an initial hemorrhage of 27 mL/kg for 10 minutes. During the next 75 minutes another 8 mL/kg of blood was withdrawn at a steady rate. The resuscitation fluids were then infused for 45 minutes during which the third continuous hemorrhage of 8 mL/kg was performed. The animals were randomized to five groups: 1) sham hemorrhage (n = 6); 2) sham resuscitation (n = 7); 3) Lactated Ringer's resuscitation, three times the volume of shed blood (n = 8); 4) Ketone Ringer's (containing 28 mEq/L of beta-hydroxybutyrate) resuscitation, three times the volume of shed blood (n = 7); and 5) plasma resuscitation, volume equal to shed blood (n = 7). The animals were sacrificed 1 hour after resuscitation and lungs were harvested. Western blot technique was used for the determination of proapoptotic protein (bax), antiapoptotic protein (bcl-2), apoptotic fragments of poly ADP-ribose polymerase, and ICAM-1. Sections of lung were also subjected to immunostaining using antibodies to bax and ICAM-1 proteins (reported as number of positive cells/mm2). RESULTS: Lactated Ringer's resuscitation caused a significant increase in pulmonary apoptosis and ICAM-1 expression compared with the sham hemorrhage group. Animals resuscitated with Ketone Ringer's solution and plasma did not show this injury pattern. CONCLUSIONS: Substitution of lactate with ketone bodies in the resuscitation fluid attenuates the expression of cellular injury markers in the lung.

Race, consanguinity and social features in Birmingham babies: a basis for prospective study.

STUDY OBJECTIVE: The aim of the study was to investigate the influence of consanguinity on children's health. DESIGN: The study is a prospective survey from birth to five years of a cohort of babies born in a multiracial community. This report details the initial findings on consanguinity. SETTING: Participating families live predominantly in three health districts of Birmingham, and were recruited in three local maternity hospitals. PARTICIPANTS: Babies of 2432 European mothers, 509 Afro-Caribbean mothers, 625 Indian mothers, 956 Pakistani mothers, and 216 Bangladeshi mothers have been enrolled in the study. Eighty mothers refused to participate. MEASUREMENTS AND RESULTS: Sociodemographic information was obtained using a structured questionnaire administered at interview. Interview data were supplemented with obstetric information from the medical records. The highest prevalence of parental consanguinity was in Pakistani Muslims (69%), whereas in Muslims from other countries it was 23%, and it was less than 1% in non-Muslims. In the majority of consanguineous Muslim pedigrees the degree of inbreeding was greater than that for first cousin parents. CONCLUSIONS: This prospective study will allow an assessment to be made about any ill health in childhood arising from parental consanguinity, about whether screening programmes are indicated for particular autosomal recessive diseases, and about whether premarital health education might be beneficial. The study has also documented parental ages in different races and this, together with the levels of parental consanguinity in all races, will be useful in genetic methods for assessing the frequency of recessive genes, the possibility of genetic heterogeneity, and whether or not parental age effect exists for new mutations of specific genetic disorders.

Portal vein thrombosis in the adult: surgical implications in an era of dynamic imaging.

Extrahepatic portal vein thrombosis (EHPVT) is the leading cause of variceal hemorrhage in patients with healthy livers; however, in an era of dynamic imaging, the incidental discovery of EHPVT places a special burden on the surgeon to understand the surgical implications of the disease in this setting. During the period 1989 to 1995, 23 patients (12 males and 11 females) were found to have EHPVT. In 20 (87%), this was an unexpected finding on ultrasound (11 of 23), abdominal CT scan (9 of 23), or both (9 of 23). In two patients, the diagnosis was suspected and confirmed with angiography, whereas in the other, the lesion was discovered at surgery. Only seven (30%) had hemorrhage as a presenting complaint. More typically (61%), abdominal pain alone or pain with sepsis was the indication for evaluation. In 20 patients (87%), there was an identifiable etiology for the EHPVT. A total of 15 operations were performed on 12 patients (52%), in 7 (4, variceal hemorrhage, and 3, bowel ischemia) as a direct consequence of the EHPVT and in five, for conditions not directly related to the EHPVT. Three of the 23 patients (13%) died, two (17%) following surgery and one (9%) from advanced malignant disease. No patients with hemorrhage (seven), even those who required a shunt for decompression (three) or devascularization (one), died. We found that the diagnosis of EHPVT is usually not related to variceal hemorrhage, but rather, abdominal symptoms that serve as an indication for the imaging study. Three subsets of patients emerged: (1) those requiring no surgery (11 patients), (2) those requiring surgery related to hemorrhage (4 patients), and (3) those requiring surgery for conditions other than varices (8 patients). In any of these circumstances, mortality (13%) was related to the underlying disease process rather than EHPVT. Given the earlier recognition of EHPVT, the natural history of the disease has been altered, with outcome reflecting the underlying disease rather than the sequelae of portal hypertension.

Does resuscitation produce a reperfusion injury?

Conceptually, shock with resuscitation should produce cellular changes that parallel those observed in a single organ exposed to ischemia with reperfusion, i.e., a transient worsening of the injury pattern after reperfusion with the degree of recovery reflecting the magnitude of the ischemic injury. To test this hypothesis, 74 male Sprague Dawley rats (300-400 g) were randomized into two groups with controls and exposed to 1) hemorrhagic shock (mean arterial pressure < 50 mm Hg) for 2 hours before sacrifice, or 2) shock (2 hours) with reinfusion of shed blood over 1 hour before sacrifice. Mean arterial pressure, blood loss, serum lactate, base excess, and bicarbonate were serially measured to determine the degree of tissue ischemia. At sacrifice, hepatic mitochondrial function was determined by the respiratory control ratio. Our findings were as follows: 1) Hemorrhagic shock produced significant (P < 0.001) tissue ischemia and impairment of mitochondrial function (P < 0.001), 2) resuscitation rapidly corrects the metabolic sequelae of tissue ischemia, and 3) mitochondrial function was unaffected by resuscitation. We conclude that resuscitation rapidly corrects the tissue ischemia associated with hemorrhagic shock, without producing any measurable reperfusion injury at the mitochondrial level.