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Background: Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients' survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases., Objectives: In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years., Materials and Methods: All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score)., Results: Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis., Conclusions: Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.

Objective: Incidence of CNS acquired demyelinating syndrome (ADS), especially multiple sclerosis (MS) in children, appears to be on the rise worldwide. The objective of this study was to determine prevalence, clinical presentation, neuroimaging features, and prognosis of different types of ADS in Iranian children., Materials & Methods: During the period 2002-2012, all the patients (aged 1-18 years) with ADS, such as MS, acute disseminated encephalomyelitis (ADEM), optic neurotic (ON), Devic disease, and transverse myelitis (TM), referred to the pediatric neurology ward, Nemazee Hospital, Shiraz University of Medical Sciences, were included in this study. Demographic data, clinical signs and symptoms, past and family history, preclinical findings, clinical course, and outcome were obtained., Results: We identified 88 patients with ADS in our center. The most prevalent disease was MS with 36.5% (n=32), followed by AEDM 26.1% (n=31), ON 17% (n=13), TM 15.9% (n=14), and Devic disease 4.5% (n=4). MS, ON, TM were more common among females while ADEM was more common in males. Children with ADEM were significantly younger than those with other types of ADS. Family history was positive in 10% of patients with MS. Previous history of recent infection was considerably seen in cases with ADEM. Clinical presentation and prognosis in this study was in accordance with those in previous studies on children., Conclusion: In this study, the most common type of ADS was MS, which was more common in female and older age cases. ADEM was more common in male and younger children. ADEM and ON had the best and Devic disease had the worst prognosis.

Objectives: The first liver transplant program in Tehran was started at Tehran University of Medical Sciences in 2002. The purpose of this study was to evaluate patient outcomes in this program., Materials and Methods: From January 2002 to February 2013, there were 172 deceased-donor orthotopic liver transplants performed in 166 patients, including revision transplant in 6 patients. Outcomes were evaluated for 4 phases of the program: (1) phase 1 (2002 to 2005; 9 transplants); (2) phase 2 (2006 to 2009; 41 transplants); (3) phase 3 (2010 to 2011; 49 transplants); and (4) phase 4 (2012 to 2013; 73 transplants)., Results: The most frequent indications for liver transplant included cryptogenic cirrhosis, autoimmune hepatitis, and hepatitis B and C cirrhosis. During the progression from phase 1 to 4, there were significant decreases in median cold ischemia time, operative time, and transfusions (platelets, packed red blood cells, and fresh frozen plasma). The most frequent complications included infection and acute rejection. The overall median follow-up for all patients was 26 months (range, 9-144 mo). Frequency of 1-month, 3-month, 1-year, and 2-year survival increased from phase 1 to 4. Kaplan-Meier plots showed significant improvement in patient survival from phase 1 to 4 (P ≤ .001). The most common causes of death were sepsis and bleeding., Conclusions: Clinical outcomes with deceased-donor liver transplant may be improved with a cooperative multidisciplinary team, coordinated care from different specialties, increased experience, and modifications of anesthetic and surgical techniques. Comprehensive unified written protocols for preoperative, perioperative, and postoperative treatment may help improve outcomes after sufficient experience is achieved.

Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.

Although fluctuations in the waiting time series have been studied for a long time, some important issues such as its long-range memory and its stochastic features in the presence of nonstationarity have so far remained unstudied. Here we find that the "waiting times" series for a given increment level have long-range correlations with Hurst exponents belonging to the interval 1/2

The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases. Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 µg/ml SCE. Cultures were evaluated by two-color flow cytometry for percent representation of CD3+ IL8+ and CD3+TNF-α cells which express interleukin-8 (IL-8), and tumor necrosis factor-α, (TNF-α+) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE). SCE dosage ranges of 0.5-100 µg/ml in cell cultures significantly suppressed LPS-increased CD3+TNF-α+ and CD3+IL8+ representation from all participants (p < 0.05), with greater pharmacological effect noted in suppression of CD3+TNF-α+ noted in cells from T2DM patients versus healthy control subjects. These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0.05). Since TNF-α and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: Adipocytokines have been reported to contribute to the pathogenesis of colorectal cancer (CRC). The aim of this matched case-control study was to explore circulating novel adipocytokines, such as serum visfatin, omentin-1 and vaspin levels in patients with CRC., Method: Serum visfatin, omentin-1, and vaspin levels were measured in 69 subjects (39 patients with colorectal cancer and 30 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods., Results: Compared with the controls, patients with CRC had significantly higher circulating omentin-1 (203.23 vs 9.12 ng/ml, p < 0.0001) visfatin (4.03 vs 2.01 ng/ml, p < 0.0001) and vaspin (0.54 vs 0.31 ng/ml, p = 0.015) levels. After adjustment for covariates (age and body mass index), patients with CRC had significantly higher serum omentin-1 (p < 0.0001), visfatin (p < 0.0001), and vaspin (p = 0.040) levels than the control group. Furthermore, the results did not change when age and waist-to-hip ratio were considered as covariates in the general linear models., Conclusions: The observed higher levels of omentin-1, visfatin, and vaspin in patients with CRC, independent of measures of obesity, suggest that these adipocytokines may have a potential role in the development of CRC through mechanisms other than the indirect mechanisms that are active in the association between obesity and CRC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Diabetes continues to be an overwhelmingly prevalent endocrine disorder that leads to several micro- and macrocomplications. It has been widely accepted that changes in dietary habits could induce or prevent the onset of diabetes. It is shown that low carbohydrate ketogenic diet (LCKD) is effective in the amelioration of many of the deleterious consequences of diabetes. However, its role in preventing the onset of diabetes is not understood. Therefore, this study is focused on the effect of LCKD in preventing the induction of diabetes using streptozotocin (STZ) in rats by biochemical and histological methods. Forty-two Wistar rats weighing 150-250 g were used in this study. The animals were divided into three groups: normal diet (ND), low carbohydrate ketogenic diet (LCKD), and high carbohydrate diet (HCD). Specific diets ad libitum were given to each group of animals for a period of 8 weeks. Each group was further subdivided into normal control, sham control and diabetic groups. Animals in the diabetic group were given a single intraperitoneal injection of STZ (55 mg/kg). All the animals were sacrificed 4 weeks after the injection of STZ. Daily measurements of food and water intake as well as weekly measurement of body weight were taken during the whole 12 weeks of the experiment. After injecting with STZ, the blood glucose level of all the groups increased significantly except for the group fed on LCKD (p value<0.01). Also, food intake, water intake and urine output were significantly increased in all groups except for the LCKD group (p value<0.01). There was also a significant decrease in the weight gain of the animals that were fed on a LCKD as compared to other groups (p value<0.05). Although, substantial decrease in the number of β cells was noticed in diabetic rats, there were no change in the number of β cells in the LCKD treated diabetic animals as compared to LCKD control group. The results presented in this study, therefore, suggests that LCKD prevents the development of diabetes using streptozotocin in rats., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Oesophageal cancer is endemic in some regions of the Islamic Republic of Iran and efforts have made to find factors that play a role in its prognosis. We retrospectively examined the correlation of serum alkaline phosphatase (ALP) levels with several clinicopathological characteristics of 207 cases of oesophageal carcinoma. The mean ALP level in patients with lymph node involvement was significantly higher [141 (SD 77) U/L] than with node negative cancers [116 (SD 63) U/L]. Patients with ALP levels 165 U/L were 3.29 times more likely to have lymph node involvement than patients with ALP levels < or = 165 U/L. There was no statistically significant correlation between ALP level and sex, age, tumour histological type, site and size of tumour, depth of penetration, distant metastasis, degree of differentiation, presence of lymphatic invasion and presence of simultaneous multiple cancers. Elevated ALP in patients with oesophageal cancer may predict lymph node involvement.

Background and Aims: Temporomandibular disorders (TMDs) are the most common condition affecting the tem-poromandibular joint and associated structures. The aim of this study was the epidemiologic evaluation of TMDs and re-lated factors in a group of Iranian adolescents., Materials and Methods: This descriptive cross-sectional survey included a sample of800 high school students (400 girls and 400 boys) aged 14 to18 years, in Mashhad, Iran, selected using cluster sampling. Examiners completed question-naires and performed the clinical examinations. Data were analyzed with the Chi-square and Fisher exact tests., Results: The prevalence of TMDs in the studied sample was 34.7%. The most common signs of TMDs were clicking, muscle tenderness and TMJ tenderness. The most prevalent predisposing factors of TMDs were clenching, premature con-tact in protrusive movement and bruxism. A clear predominance was seen in girls (40.5%) compared with boys (29%) (P = 0.001)., Conclusion: Signs and symptoms of TMDs were prevalent in Iranian adolescents with a clear female predominance.

Background/aim: Thrombocytosis is found to be associated with unfavorable prognosis in esophageal carcinoma. Platelets produce thymidine phosphorylase which is a platelet-derived endothelial cell growth factor with angiogenic activity. Increased platelet count may be translated into enhanced tumor growth. We examined the relation between platelet count and several prognostic variables in patients with esophageal cancer., Patients and Methods: Three hundred and eighty-one cases with esophageal cancer that underwent esophagectomy in a referral cancer institute during a 5-year period were studied retrospectively. The relation between preoperative platelet count and patient age, gender, site of tumor, presence of multiple cancers and clinicopathological characteristics including histological type, tumor size, depth of penetration (T), lymph node involvement (N), distant metastasis (M), degree of differentiation, presence of vascular, lymphatic and perineural invasion was examined., Results: Squamous cell carcinoma (SCC) constituted 93% and adenocarcinoma 7% of cases. Most of patients were in stage III, followed by stage II. The mean platelet count was 245±76 (Χ 10(9)/L). There was no statistically significant correlation between platelet counts with prognostic factors except a weak linear correlation between platelet count and and tumor size (P = 0.03, Pearson correlation coefficient: 0.16). Patients with adenocarcinoma had a higher platelet count than those with SCC (P = 0.003)., Conclusion: Platelet count does not correlate with prognostic factors in esophageal cancer. However, it is significantly different between SCC and adenocarcinoma of esophagus.

Statistical behavior and scaling properties of isoheight lines in three different saturated two-dimensional grown surfaces with controversial universality classes are investigated using ideas from Schramm-Loewner evolution (SLE&#95;{κ}). We present some evidence that the isoheight lines in the ballistic deposition (BD), Eden and restricted solid-on-solid (RSOS) models have conformally invariant properties all in the same universality class as the self-avoiding random walk (SAW), equivalently SLE&#95;{8/3}. This leads to the conclusion that all these discrete growth models fall into the same universality class as the Kardar-Parisi-Zhang (KPZ) equation in two dimensions.

Background: Green tea has been shown to repair fasting-induced mucosal damage in rat intestine. The aim of this study was to elucidate the underlying mechanism., Methods: Five groups of rats were used. Group 1 had free access to chow diet and water, and those in group 2 were fasted for 3 days. Animals in group 3 were fasted for 3 days, then were allowed drinking water for a further 7 days. Groups 4 and 5 were fasted for 3 days, then given drinking water containing green tea or vitamin E respectively for 7 days. Blood was collected for estimation of total plasma antioxidants, and jejunal samples were used for immunohistochemical analysis of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and for estimation of myeloperoxidase (MPO) activity., Results: Use of green tea was associated with a significant increase in total plasma antioxidants (P < 0.001), and mucosal SOD (P < 0.001), catalase (P = 0.006) and GPx (P = 0.017), but a significant decrease in MPO activity (P < 0.001). Vitamin E produced similar changes, but the effects were smaller., Conclusion: Green tea reverses the fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect., (2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Surgery is still the best way for treatment of esophageal cancer. The increase in life expectancy and the rising incidence of esophageal tumors have led to a great number of elderly candidates for complex surgery. The purpose of this study was to evaluate the effects of advanced age (70 years or more) on the surgical outcome of esophagectomy for esophageal cancer at a single high-volume center., Materials and Methods: Between January 2000 and April 2006, 480 cases with esophageal cancer underwent esophagectomy in the referral cancer institute. One hundred sixty-five patients in the elderly group (70 years old or more) were compared with 315 patients in the younger group (< 70 years). All in-hospital morbidity and mortality were studied., Results: The range of age was 38-84 years, with a mean of 58.7. The mean age of the elderly and younger groups was 74 and 53.2, respectively. In the younger group, 70 patients (22.2%) and in the elderly group, 39 patients (23.6%) were complicated (P 0.72).The most common complications in the two groups were pulmonary complications (9.8% in younger and 10.3% in elderly) (P 0.87). Rates of anastomotic leakage and cardiac complications were also similar between the two groups. Hospital mortality rates in younger and elderly patients were 2.8% and 3%, respectively. There was no significant difference between the two groups in morbidities and mortality (P-value > 0.05)., Conclusions: With increased experience and care, the outcomes of esophagectomy in elderly patients are comparable to young patients. Advanced age alone is not a contraindication for esophagectomy.

Appreciation of stochastic Loewner evolution (SLE&#95;{kappa}) , as a powerful tool to check for conformal invariant properties of geometrical features of critical systems has been rising. In this paper we use this method to check conformal invariance in sandpile models. Avalanche frontiers in Abelian sandpile model are numerically shown to be conformally invariant and can be described by SLE with diffusivity kappa=2 . This value is the same as value obtained for loop-erased random walks. The fractal dimension and Schramm's formula for left passage probability also suggest the same result. We also check the same properties for Zhang's sandpile model.

Major complications after maxillary orthognathic surgery are fortunately uncommon when executed properly. However, segmental necrosis has been reported. When this occurs, comprehensive reconstruction of the maxilla becomes difficult because both hard and soft tissues are lost. Use of a free flap such as the fibula for this purpose is difficult because it is bulky. We report a 40-year-old woman who presented with a defect of the anterior maxilla that occurred after necrosis of the premaxilla, which we treated with a modified prefabricated osteocutaneous free fibula flap and dental implants with long-term follow-up. The modified prefabricated free fibula flap is suitable for maxillary reconstruction.

Autogenous bone grafting of uncontained tibial bony defects was carried out in 18 patients during a cemented total knee arthroplasty. American Knee Society scores were used to compare the results of the grafted group with those of a control group of 132 total knee arthroplasty patients without a significant tibial bony defect. The patients were followed up for 10 years. There was a statistically significant difference in the mean knee scores of the 2 groups at the preoperative assessment. Postoperative results were comparable between the 2 groups, indicating a significant and similar improvement in the knee scores of the grafted and control groups. Autogenous bone grafting is an easy and reproducible method of dealing with uncontained tibial bony defects during a total knee arthroplasty.

Nongenetic breast cancer risk factors have never been evaluated in Kuwait. Accordingly, we aimed at examining these factors as well as the immune profile of the patients. Fifty stage I breast cancer patients and 50 age group-matched normal controls were assessed for the level of their peripheral blood lymphocyte subsets and for risk factors associated with their demographic and reproductive characteristics and with diet. The percentages of CD4+ T lymphocytes, CD4+:CD8+ ratio, and CD19+ B lymphocytes were significantly higher in the patients as compared to controls, while the percentages of CD8+ T lymphocytes and natural killer (CD56+) cells were significantly reduced. Risk factors associated with the disease included higher BMI, lack of regular exercise and physical activity in the past 5 years, early age at menarche, late age at first pregnancy, lack of previous information about breast cancer, hormonal therapy, and presence in Kuwait during the invasion/liberation. Other parameters included significantly more frequent consumption of carbohydrate, sweets, animal fat, and vegetable oil (margarine) and less frequent consumption of fresh vegetables and olive oil. This is the first study to highlight the environmental risk factors associated with breast cancer among the Kuwaiti women. We recommend introducing a nationwide campaign to further investigate these factors and to address them accordingly.

Purpose: To determine whether flexion contracture continues to improve up to 5 years after total knee arthroplasty (TKA)., Methods: Records of 200 women and 123 men (mean age, 72 years) with osteoarthritis and preoperative flexion contracture were reviewed. 155 (48%) involved the left knee and 168 (52%) the right knee. Patients were assessed clinically before TKA and one and 5 years later, by a single researcher using a goniometer to measure flexion contracture, range of movement, maximum flexion, and the Knee Society Score. In all patients the same prosthesis design was used. The surgical technique was standard and involved a medial parapatellar approach with bone resection., Results: All variables improved significantly from pre-TKA to one-year post-TKA and from one-year post-TKA to 5-year post-TKA; respectively the mean flexion contracture decreased from 11 to 3 to 2 degrees; the mean knee range of movement increased from 90 to 103 to 107 degrees; the mean maximum flexion increased from 101 to 106 to 109 degrees; and the mean Knee Society Scores increased from 39 to 87 to 90., Conclusion: Functional outcome and flexion contracture may continue to improve up to 5 years after TKA.

Many patients who undergo total hip arthroplasty still have a high level of activity. A popular low-intensity exercise in this patient group is golf. This study sought to investigate the group of patients who have had a hip arthroplasty procedure and who list golf as one of their pastimes, assessing the impact of surgery on their ability to participate in and perform at the game. Seven hundred fifty consecutive patients who had undergone total hip arthroplasty were sent questionnaires relating to their golfing habits. There was no significant change from their predisease state to their 1-year postoperative golf performance and level of participation. Harris hip scores were significantly higher for the golfing population both preoperatively and at all stages of follow-up.

The aim of this study was to assess the effects of alpha-interferon and alpha-tocopherol (vitamin E), or a combination of both, in reversing hepatic fibrosis following the induction of cirrhosis using thioacetamide by histological and biochemical analysis. Fifty male Wistar rats were used in this study. The animals were divided equally into five groups. Animals in group I were used as controls. The remaining animals (groups II-V) were provided with 0.5 g/L of thioacetamide in order to induce liver cirrhosis. Group II animals were used as the cirrhotic control. Animals of groups III, IV and V were given alpha-interferon, alpha-tocopherol and interferon together with alpha-tocopherol, respectively, for 30 days. After 30 days the animals were killed and following gross morphological examination of the liver, the hepatic tissues were processed for histological analysis and the serum was used for liver function tests. Morphological analysis showed a decrease in the number of nodules on the surface of the liver in both interferon- as well as vitamin E-treated cirrhotic rats. Histopathological analysis showed that the abnormalities of the cirrhotic liver were partially reversed and liver function tests showed an overall improvement following treatment of animals of groups III, IV and V. Combination therapy using both interferon and alpha-tocopherol did not have any substantial effect on the rats compared with that when they were given separately. These findings suggest that alpha-interferon and alpha-tocopherol may have therapeutic value in reversing liver cirrhosis.

Objective: To evaluate laparoscopic adjustable gastric banding and the 'pars flaccida' techniques for treating morbidly obese patients., Subjects and Methods: Between May 1999 and July 2002, 64 patients underwent laparoscopic adjustable gastric banding. The 'perigastric' technique was performed in the first 31 patients. From September 2000 the band was positioned according to the 'pars flaccida' technique in the remaining 33 patients. The patients were divided into three groups: group 1 - 'perigastric' technique using Lap-Band size 9.75 and 10 cm (31 patients); group 2 - 'pars flaccida' technique using Lap-Band size 10 cm (12 patients), and group 3 - 'pars flaccida' technique using the Swedish band (21 patients). There were 58 females and 6 males with a mean age of 36.6 years (range 17-56). The preoperative mean body mass index was 46.2 kg/m(2)., Results: Band slippage occurred in 10/31 patients (32.2%) of group 1, 3/12 patients (25%) of group 2 and none in group 3 patients (p < 0.01)., Conclusion: The 'pars flaccida' technique significantly reduces the incidence of postoperative slippage after gastric banding. This complication is further reduced in the Swedish band group. Furthermore, we do not recommend using the 10-cm Lap-Band in the 'pars flaccida' technique., (Copyright 2007 S. Karger AG, Basel.)

We studied 70 consecutive patients with adolescent idiopathic scoliosis who underwent corrective surgery. They were divided into two groups. In the study group of 38 patients one or more modern blood-conservation measures was used peri-operatively. The 32 patients in the control group did not have these measures. Both groups were similar in regard to age, body-weight, the number of levels fused and the type of surgery. Only two patients in the study group were transfused with homologous blood and these transfusions were 'off-protocol'. Wastage of autologous pre-donated units was minimal (6 of 83 units). By contrast, all patients in the control group were transfused with homologous blood. In the study group there was a significant decrease (p = 0.005) in the estimated blood loss when all the blood-conservation methods were used. The use of blood-conservation measures, the lowering of the haemoglobin trigger for transfusion and the education of the entire team involved in the care of the patient can prevent the need for homologous blood transfusion in patients undergoing surgery for adolescent idiopathic scoliosis.

The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells.

To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with >3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.

Objectives: The aim of this prospective study was to evaluate the safety and feasibility of laparoscopic splenectomy (LS) in patients with hematological disorders of the spleen., Subjects and Methods: Between 1999 and 2001, 15 patients (11 female and 4 male), with a mean age of 30 years, underwent LS after preoperative evaluation. If difficulties were encountered in LS, one trocar site incision was enlarged to 7-8 cm to engage the left hand for hand-assisted laparoscopic splenectomy (HALS) and the procedure was completed. Various parameters were reported, including spleen size as assessed by ultrasound scan, postoperative mortality and morbidity rates, accessory spleen removal, conversion rate, operative times and length of hospital stay. LS was successfully completed in 9 patients (60%) and HALS was performed in 4 patients (26.6%). Two patients required conversion to open splenectomy., Results: The mean operative time was 209 min and the mean hospital stay was 8.1 days. The hospital stay was significantly longer among HALS patients than LS patients. The mean age of patients and splenic size were associated with a significantly higher conversion rate. No deaths were attributed to the procedure. Complications occurred in 2 of 15 patients. Accessory spleens were identified in 2 patients., Conclusions: LS is both a safe and feasible procedure, but it requires great technical care to avoid serious complications., (Copyright 2004 S. Karger AG, Basel)

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.

Objective: To compare the validity of a careful clinical examination with venous Doppler studies in the management of patients presenting with varicose veins., Subjects and Methods: Ninety-five consecutive patients presenting with varicose veins from September 1998 to August 1999 were included in this study. Of the 95 patients, 52 were males and 43 females. Eighty-four were expatriate laborers and 11 Kuwaiti nationals. Seventy-one were active workers under the age of 30. All of the patients underwent a full clinical examination for varicose veins, and a management plan was developed for each patient prior to Doppler venous study. The results of the Doppler studies were then compared with the clinical examination results, and the management plan was changed, if necessary, based on the Doppler results., Results: Both clinical and Doppler examinations were equally effective in diagnosing primary varicose vein and identifying sites of venous incompetence. A family history for varicose veins was found in 21% and standing for a long period of time was a risk factor in 51% patients. The most common symptoms were pain and heaviness. Doppler study findings were useful in changing the management plan of 14 (15%) patients, 6 with recurrent varicose vein and 8 obese patients with chronic venous insufficiency. The majority of the patients (n = 82) benefited from surgery and were free of symptoms., Conclusion: This prospective study demonstrated that detailed clinical examination was sufficient to diagnose most patients suffering from primary varicose veins. Doppler vascular studies were useful in changing the treatment modality for those presenting with recurrent varicose vein or obese patients with signs and symptoms of chronic venous insufficiency with no clinically clear varicosity., (Copyright 2004 S. Karger AG, Basel)

Objective: Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting., Methods: Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination., Results: In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage., Conclusion: The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.

Contraction of smooth muscles of the vas deferens plays an important role in the propulsion of sperm into the pelvic urethra. This study examined the influence of external Mg2+ concentration on reactivity of the rat vas deferens to electrical stimulation in vitro. Vasa deferentia isolated from adult male rats were set up in tissue baths containing physiological salt solution at 37 degrees C and were stimulated electrically. Thereafter, increasing concentrations of Mg2+ were added to the bath and their effects on electrically evoked contractions were recorded. The effect of external Mg2+ depletion on evoked contractions was also examined. External Mg2+ depletion enhanced the contractile response to electrical stimulation while increasing external Mg2+ concentration inhibited the contractions. The inhibitory effect of Mg2+ was partially reversed by increasing extracellular Ca2+ concentration and was not additive with nifedipine. The results indicate that reactivity of the vas deferens to electrical stimulation is modulated by extracellular Mg2+ concentration. The possible relevance of these data to sperm transport through the vas deferens is discussed.

Although magnesium is involved in many biological process and it is found higher levels in semen than serum, its role in human semen has not been elucidated. This investigation was conducted to evaluate the relationship between premature ejaculation and the levels of seminal magnesium. The levels of magnesium, zinc, copper, and selenium were evaluated with an atomic absorption spectrophotometer in serum and seminal plasma in 3 groups of men: (a) normal sperm parameters (15) (b) oligoasthenozoospermia (15), and genuine premature ejaculation (9). There were normal serum and semen levels of all the elements in the three groups, but significantly lower seminal plasma magnesium levels in men with premature ejaculation. The hormonal profile, body mass index (BMI) had no association with premature ejaculation. Decreased levels of magnesium gives rise to vasoconstriction from increased thromboxane level, increased endothelial intracellular Ca2+, and decreased nitric oxide. This may lead to premature emission and ejaculation processes. Magnesium is probably involved in semen transport. More research into the role of magnesium in the male physiology of reproductive tract, especially its association with premature ejaculation, is advocated.

Background: Appendicectomy for suspected acute appendicitis is a common procedure. The rate of normal appendices unnecessarily removed remains high (15-30%) despite several techniques and investigations used to improve the diagnostic accuracy. Many studies investigated the role of raised C-reactive protein in improving the diagnosis of acute appendicitis, but with conflicting results. This study emphasies the impact of a normal (rather than raised) serum C-reactive protein in reducing the rate of negative explorations., Methods: In a double blind study, blood for the measurement of serum C-reactive protein (CRP) was collected pre-operatively from 78 patients just before going to the operating room for appendicectomy. The histopathology of the 78 appendices were grouped into positive (acute appendicitis) and negative (normal appendix). White blood count (WBC), CRP and the histopathology findings were correlated., Results: In patients with histopathologically proven acute appendicitis both the WBC count and serum CRP level were significantly raised (P = 0.025 and P < 0.000,1 respectively). Serum CRP level was normal in 13 out of 15 negative explorations (normal appendix on histopathology). The specificity and sensitivity of serum CRP was 86.6% and 93.6%, respectively., Conclusion: A normal pre-operative serum CRP measurement in patients with suspected acute appendicitis is most likely associated with a normal appendix. Deferring surgery in this group of patients would probably reduce the rate of unnecessary appendicectomies.

Background: Medical treatment of peptic ulcer is highly successful, and the eradication of Helicobacter pylori (H. pylori) reduces ulcer recurrence. However, the incidence of perforated duodenal ulcer and its associated mortality have not been reduced by modern methods of therapy. Laparoscopic simple closure and omental plug by suturing, fibrin glue, and stapler have been successful., Methods: Over a 1-year period (1996-97), 21 patients with perforated duodenal ulcer were operated on in our hospital by laparoscopic simple closure and omental patch. The mean age was 36.4 +/- 11.8 years (range, 18-61). Twenty patients were male (93.7%). The mean duration of pain was 9.1 +/- 11.7 hs (range, 2-48). Three patients had a previous history of duodenal ulcer (14.3%), and another three (14.3%) patients had a history of nonsteroidal antiinflammatory drug (NSAID) intake. Erect chest radiograph showed that 19 patients had air under the diaphragm (90.5%). Sixteen patients (76.2%) had frank pus in the abdomen, and five patients had a minimal peritoneal reaction (23.8%)., Results: The mean operative time was 71.6 +/- 24.6 mins (range, 40-120), and the mean hospital stay was 5.2 +/- 1.6 days (range, 3-9). The mean time to resume oral fluids was 3.1 +/- 0.8 days (range, 2-4). Only one patient was reoperated due to leakage identified by gastrographin swallow., Conclusions: This procedure is safe and efficient; however, further study of its long-term effectiveness and comparability to existing therapy is still needed.

Recent studies show that structural parameters of bone, obtained from computerized image analysis of radiographs, can improve the noninvasive determination of bone strength when used in conjunction with bone density measurements. The present study was designed to assess the ability of image features alone to predict the mechanical characteristics of bones. A multifactorial model was used to incorporate simultaneously a number of characteristics of the image, including periodicity and spatial orientation of the trabeculae. Fifteen pairs (29 specimens) of unembalmed human distal radii were used. The cancellous bone structure was determined using computerized spectral analysis of their radiographic images and the bones were tested to failure under compression. Multilayered perceptron neural networks were used to integrate the various image parameters reflecting the periodicity and the spatial distribution of the trabeculae and to predict the mechanical strength of the specimens. The correlation between each of the isolated image parameters and bone strength was generally significant, but weak. The values of mechanical parameters predicted by the neural networks, however, had a very high correlation with those observed, namely 0.91 for the load at fracture and 0.93 for the ultimate stress. Both these correlations were superior to those obtained with dual-energy X-ray absorptiometry and with the cross-sectional area from CT scans: 0.87 and 0.49 respectively. Our observation suggests that image parameters can provide a powerful noninvasive predictor of bone strength. The simultaneous use of various parameters substantially improved the performance of the system. The multifactorial architecture applied is nonlinear and possibly more effective than traditional multicorrelation methods. Further, this system has the potential to incorporate other non-image parameters, such as age and bone density itself, with a view to improving the assessment of the risk of fracture for individual patients.

The aim of the study was to investigate the role of zinc therapy in 125 male cigarette smokers with infertility. The mechanism involved in the zinc/cadmium relationship was evaluated through the effect of a zinc-deficient diet and supplementation on testes of male adult Sprague-Drew rats. Heavy smoking was associated with low sperm count, motility, and morphology and increased seminal cadmium levels. Zinc therapy improved sperm quality and increased seminal IL-4, but reduced TNF-alpha and IFN-gamma. A zinc-deficient diet led to high cadmium testicular accumulation comparable with those supplemented with cadmium. Cadmium had a linear correlation with TNF-alpha and IFN-gamma, but not with IL-4. Cytology of testicular aspirate and histopathology were normal in supplemented groups as in controls. These results indicate that zinc modulates the putative effect of cadmium through its enhancement of T-helper 2 cytokines expression and down-regulation of T-helper 1 cytokines.

The tumour markers CEA, AFP, CA 125 and CA 199 were analyzed in a group of apparently healthy subjects in Kuwait. The sample (n = 394) included both genders in the population with a mean age of 38 (S.d. 12.0) years. The distribution of CEA levels values was significant different (Mann-Whitney U test) between Kuwaiti and non-Kuwaiti. The distribution of AFP levels was found to be the same in all groups. The distribution of CA 125 levels was significantly higher in females than in males, both in Kuwaiti and non-Kuwaiti. The distribution of CA 19-9 values was found to be significantly higher in the Kuwaiti female group when compared to the males. The upper reference level was defined as the 95 percentile of the normal values in each group. In the total population the reference level of AFP was 5.6 micrograms/l and of CA 19.9 43 kU/l. The reference level of CA 125 was 16 U/l in males and 24 kU/l in females, respectively. The CEA reference level in Kuwaitis was 6.9 micrograms/l and in non-Kuwaitis 4.4 micrograms/l. The results indicated the importance of determining the reference levels of tumour markers for each individual laboratory. It was also emphasized that care should be taken on the impact of 95 percentiles of normal and benign disease groups.

Effects of selenium deficiency, induced by thioacetamide, were investigated in rats. Thioacetamide (0.3 g/L) given in drinking water, as expected, caused a significant loss of selenium from the liver. It was accompanied by liver cirrhosis and a significant increase in the liver weight as well as liver to body weight ratio. A significant loss of selenium from spleen was also accompanied by an increase in its weight. Weights of lungs, testis and kidney, however, were not affected by thioacetamide and there was no change in their selenium content. Plasma levels of selenium were significantly reduced in the thioacetamide treated group. All these changes were confirmed to be due to selenium deficiency caused by thioacetamide, as supplementation with selenium reversed these changes. The mode of action of selenium is unknown but may involve anti-oxidant defense mechanisms.

Objectives: The role of zinc therapy on infertility caused by defective sperm quality is examined., Study Design: In this study, 100 men with asthenozoospermia were randomised into two groups--250 mg twice daily zinc therapy for 3 months and no therapy. The patients were followed up for another 6 months. Sperm parameters, circulating antisperm antibodies, sex hormones and T helper cytokines were evaluated before and after treatment for the two groups., Results: There was significant improvement in the sperm quality; sperm count (P<.02), progressive motility (P<.05), fertilising capacity (P<.01) and a reduction in the incidence of antisperm antibodies (P<.01). Zinc/cadmium was higher in the zinc therapy group (P<.02). T helper cytokine, interleukin-4 level was significantly higher after zinc therapy (P<.02) while TNFalpha showed a significant decrease (P<.05)., Conclusions: Zinc therapy has a role in improving sperm parameters in men with asthenozoospermia, probably through its membrane stabilising effect as an antioxidant and its effect on cellular and humoral immunity by reducing the levels of antisperm antibodies and TNFalpha and increasing that of IL-4.

Cirrhotic liver is predisposed to bacterial infections. Different species of bacteria including Escherichia coli, Enterobacter and Bacteroides fragilis were found to colonize thioacetamide-induced cirrhotic rat liver. Zinc treatment of the cirrhotic rats significantly corrected the histological and histochemical changes in the liver. However, this reversal with zinc treatment was not accompanied by any change in the bacterial colonies in the liver. The study shows that cirrhosis predisposes liver to bacterial colonization and the process is not reversible despite the partial reversal of the cirrhotic changes.

Oligo-elements such as zinc (Zn), selenium (Se) and copper (Cu) have a significant influence on the function of the immune system. Various immunological and inflammatory changes are known to occur in patients undergoing cardiopulmonary bypass. The aim of this study was to evaluate changes in serum oligo-elements levels during and following cardiopulmonary bypass. The serum levels of Zn, Se and Cu were determined in 67 consecutive patients, with coronary artery disease admitted for coronary artery bypass grafting. Blood samples for oligo-elements, analysis were withdrawn into metal-free tubes just prior to the start of cardiopulmonary bypass; at 30, 60 and 90 min into cardiopulmonary bypass; following weaning from cardiopulmonary bypass; 30 min after termination of cardiopulmonary bypass; at 24 h; and on the 5th postoperative day. Trace elements analyses were performed using atomic absorption spectrophotometry. Interleukin 6 and 8, as well as serum albumin, creatine phosphokinase, lactate dehydrogenase and creatine phosphokinase-MB fractions were also analyzed. The mean age was 63 +/- 9 years and 91% (61) were men. The mean preoperative left ventricular function was 52 +/- 12%, Canadian Cardiovascular Society (CCS) angina class was 3.7 +/- 0.5 and 30% (20) of the operations were re-do's. All patients had normothermic cardiopulmonary bypass. Mean cardiopulmonary bypass-time was 85 +/- 31 min. One patient was lost for the recovery sampling (hospital mortality, 1.5%). Nine patients had a postoperative cardiac index < 2.0 liter/min per m2, which required pharmacological support and additional intra-aortic balloon pump in two of them. Other postoperative complications were few. There was a rapid depletion of S-selenium and S-Zn levels, which were halved at 30 min after cardiopulmonary bypass and remained low throughout the study period. The Cu/Zn ratio increased significantly at the start of cardiopulmonary bypass, which indicated an inflammatory reaction and was not normalized until the 5th postoperative day. Length of ischemia time, presence of diabetes. hypertension and hyperlipidemia did not influence the results, while a prolonged cardiopulmonary bypass-time > 120 min resulted in a higher Cu/Zn ratio than observed for shorter cardiopulmonary bypass-times. This indicates a more profound inflammatory response. Inflammatory parameters responded in the same manner as described earlier by others. These data indicate that severe loss of various oligo elements occur in patients undergoing coronary artery bypass grafting and suggests that a supplementary administration of zinc and perhaps also selenium could be appropriate during cardiopulmonary bypass.

Kuwait is a desert country where the prevailing high temperatures, low humidity, and scant vegetation suggest a low prevalence of allergy. We evaluated the prevalence of atopic sensitization (presence of allergen-specific IgE) among young adult blood donors by screening a total of 505 subjects (male: female ratio 1.6) with mean age of 28.4 years (range 18-50 years). The Pharmacia CAP-Phadiatop test, which detects serum IgE specific to most common airborne allergens, was used. Some of the specific sensitizing allergens were also identified by the related CAP-RAST method. Sensitization was detected in 223 of the 505 subjects (44.2%) screened. Kuwaiti nationals had a significantly higher prevalence rate (50.2%) than non-Kuwaitis (34.2%) (chi 2 = 8.6, P < 0.003). The highest prevalence rate was found among male Kuwaitis (53.8%). The prevalence of current or previous allergic disease (subject-reported) was 20.6%. Bermuda grass, house-dust mite (Dermatophagoides pteronyssinus), and Chenopodium album were the most prevalent sensitizing allergens, with frequencies of 53.6%, 52.7%, and 50.9%, respectively, among the sensitized subjects (corresponding to 23.7%, 23.3%, and 22.5%, respectively) for the entire population. Sensitization increased with age, but only among the expatriates, younger Kuwaitis being as frequently sensitized as the older ones. Polysensitization was found to be common. Of the 109 CAP-RAST-positive subjects, 71 (65.1%) were sensitized to more than one allergen, and 30 of these (42.3%) were sensitized to four or more allergens. These results show that atopy is highly prevalent among young adults in Kuwait, and the higher prevalence rate among nationals than expatriates suggests the involvement of genetic or local environmental factors. The results also confirm that mite and plant pollens may be major sensitizing allergens even in a desert environment.

In vitro contractility of human and sheep gallbladders to cholinergic stimulation with carbachol and the effects of indomethacin on abnormal rhythmic activity were studied. Once hundred and thirty-two gallbladders were obtained at laparoscopic cholecystectomy, 38 from patients with acute and 94 with chronic cholecystitis. In addition, 27 specimens of sheep gallbladders served as controls. Fundal preparations from patients with cholecystitis exhibit hypocontractility: no response in 72% or in the remainder a significantly reduced maximal contraction to carbachol. Regionally graded motor responses favoring propulsion of bile were abnormal in 44% of the gallbladders studied with more forceful contractions of the duct compared to the fundus. Abnormal early rhythmic activity (ERA) of fundal preparations was only detected in gallbladders of patients (in 33%) but never in controls. In 80% of these, ERA was blocked or reduced by indomethacin which can be interpreted as evidence for a prostaglandin-mediated inflammatory response. We conclude that gallbladder motility in cholelithiasis secondary to muscarinic stimulation is reduced and regionally graded motor responses favoring bile expulsion are impaired. ERA can be blocked by indomethacin.

We report a case of a 7-year-old girl in whom a vascularized fibular head with preserved epiphyseal and metaphyseal blood supply was used to reconstruct the missing lateral malleolus. Two-year follow-up showed good bony stability and growth potential of the transplanted epiphyseal plate.