Dystonia in children with acquired brain injury.

AIM: To quantify the proportion of children who develop dystonia after acquired brain injury (ABI) admitted to a tertiary paediatric intensive care unit (PICU) and analyse the trajectory of dystonia over a 6 month period. METHODS: Children's Health Ireland at Temple Street PICU electronic database was searched for key terms related to ABI from January 1, 2016 to March 14, 2021. Individuals meeting inclusion criteria were analysed, and clinical data pertinent to ABI, dystonia, treatment and outcomes were reviewed. RESULTS: Six-hundred and forty-three PICU episodes (580 patients) met search criteria for ABI, with 379 included in the final analysis. Twelve patients developed dystonia following ABI, giving an incidence of 3.2%. The incidence was higher in the hypoxia/anoxia and TBI cohort at 8.3% and 6.2%, respectively. All patients developed dystonia within the first month following ABI (50% by a week). Patients who developed dystonia compared to non-dystonia cohort had a median lower GCS on admission (4.5 versus 7.0, p value 0.032), longer median length of PICU stay (14.0 versus 3.0 days, p value < 0.001) and were older (median age 9.08 versus 4.68 years, p value 0.06). Dystonia persisted in the majority at 6 months (10/11), requiring on-going medical therapies. CONCLUSION: In our retrospective study, the estimated incidence of dystonia following ABI admitted to the PICU was 3.2%, highest in the hypoxia/anoxia (8.3%) and TBI (6.2%) cohorts. Dystonia emerged early and persisted at 6 months in the majority. This is the first review of dystonia, clinical trajectory and outcomes conducted post-PICU admission for ABI. Future prospective studies are required to determine the true prevalence and burden of disease in the PICU setting.

Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats.

OBJECTIVE: Synthetic dyes have been reported to exert detrimental effects on the health of humans. This study evaluated the effects of a diet containing tartrazine (Tz) on rats which included: i) biochemical parameters including hepatic enzymes, kidney functions and profiles of lipids; ii) markers of oxidative stress in cells by measuring concentrations of malondialdehyde (MDA) and glutathione (GSH); iii) activities of selected, key hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx); iv) pathologies of liver. Also, protective effects of three doses of curcumin (CUR), a natural food coloring agent, on these parameters in rats that had been co-exposed to Tz. MATERIALS AND METHODS: Fifty Wistar male albino rats were randomly divided into five groups: Group I, control, where rats were fed a normal diet; Group II, rats were fed normal diets containing 7.5 mg Tz/kg diet, dry mass (dm); In Groups III, IV and V, rats were fed diets containing Tz plus 1.0, 2.0 or 4.0 g CUR/kg diet, dm, respectively. Whole blood was collected after 90 d of exposure, homogenates of liver were prepared and the above analyses were conducted. RESULTS: Exposure to Tz in the diet caused statistically significant (p<0.05) greater concentrations of lipids, hepatic enzymes, and kidney function parameters as well as the indicator of oxidative stress MDA. Alternatively, activities of several antioxidant enzymes (i.e. CAT, SOD and GPx) and concentration of the substrate GSH, an indicator of non-enzymatic antioxidant capability, were significantly (p<0.05) less than those in control rats not exposed to Tz. Tz caused various histopathological changes in livers of rats, which were characterized by hemorrhage and dilatation of the central vein and sinusoids, hepatocyte necrosis, intracellular vacuolization. Co-administration of 2.0 (Group IV) or 4.0 g CUR/kg diet (Group V) with Tz significantly mitigated effects on functions of liver and kidney and the profile of relative concentrations of lipids. CUR significantly (p<0.05), and almost completely, reversed effects on enzymatic and non-enzymatic antioxidant and indicators of oxidative stress about rats fed Tz (Group II) to values in control rats. However, co-administration of 1.0 g CUR with Tz (Group III) exhibited a negligible effect on those parameters. The results of this study suggest benefits of the use of CUR, as a promising natural food additive to counteract oxidative stress caused by dietary exposure to the synthetic dye Tz due to potent protective antioxidant activity. CONCLUSIONS: Blending some natural food additives, such as CUR with diets containing synthetic dyes, could moderate potential effects of these artificial dyes. Decreasing or removing toxins in food is an essential step for the amelioration of human health status and decreasing risk of onset or progression of degenerative diseases.

Anti-diabetic molecules from Cycas pectinata Griff. traditionally used by the Maiba-Maibi.

Bioactivity guided chemical investigation on active anti-diabetic constituents of the fruits of Cycas pectinata Griff. (FCP) characterized EAFr-5 as the most potent sub fraction which significantly reduced the blood glucose level to normal in STZ induced diabetic rats. It was shown to contain the biflavonoids amentoflavone (1) and 2,3-dihydroamentoflavone (2) which exhibited significantly high inhibitory potency against α-glucosidase (IC50 8.09 ± 0.023 and 9.77 ± 0.032 µM, respectively) and α-amylase (IC50 73.6 ± 0.48 and 39.69 ± 0.39 µM, respectively). This is the first report of bioactivity guided isolation of anti-diabetic constituents from the traditionally used fruits of Cycas pectinata Griff.

Isolation and distribution of mosquito-larvicidal cry genes in Bacillus thuringiensis strains native to Saudi Arabia.

A total of 157 environmental samples were collected from 11 ecological regions across Saudi Arabia to isolate native Bacillus thuringiensis (Bt) strains. Bt isolates (n=103) were recovered by the 50% (v/v) ethanol treatment method with Bt index range of 0.01 to 0.4. Most of Bt isolates showed spherical crystals (54%), while, irregular, bi-pyramidal, and spore-attached crystal constituted 27, 16 and 3% respectively. PCR analysis with eight general and specific dipteran primers of Cry and Cyt genes, revealed positive amplification for cry4 & cyt1, and cry4A, cry4B and cyt2, and cry 10 and cry 11 genes in 28%, 26%, 22%, and 25% of tested strains respectively; whereas cry2 gene was not detected except with the reference Bt kurstaki HD-1 strain. Bioassays against Aedes caspuis and Culex pipiens larvae indicated that 11 strains displayed better larvicidal activity compared with Bacillus thuringiensis H14 (Bti) reference (LC50 0.6 µg/ml) strain against Ae. caspuis, but only two strains (620A & 633R1, LC50 of 0.09 µg/ml & 0.064 µg/ml) that gave significant enhancement. Additionally, one strain (633R1) showed LC50 similar to that of Bti H14 (LC50 0.064 µg/ml) against Cx. pipiens. With the exception of cyt primers, sequenced DNA of all positive primers amplicons revealed 95 to 99% identity in GenBank with Bacillus thuringiensis subsp. israelensis plasmid pBtoxis and also correlated with its SDS-PAGE expressed protein profiles analysis. It is hoped that our wild bio-insecticide Bt strains can be explored in future in the control of mosquito-vector borne diseases in Saudi Arabia.

Isolation and distribution of mosquito-larvicidal cry genes in Bacillus thuringiensis strains native to Saudi Arabia

A total of 157 environmental samples were collected from 11 ecological regions across Saudi Arabia to isolate native Bacillus thuringiensis (Bt) strains. Bt isolates (n=103) were recovered by the 50% (v/v) ethanol treatment method with Bt index range of 0.01 to 0.4. Most of Bt isolates showed spherical crystals (54%), while, irregular, bi-pyramidal, and sporeattached crystal constituted 27, 16 and 3% respectively. PCR analysis with eight general and specific dipteran primers of Cry and Cyt genes, revealed positive amplification for cry4 & cyt1, and cry4A, cry4B and cyt2, and cry 10 and cry 11 genes in 28%, 26%, 22%, and 25% of tested strains respectively; whereas cry2 gene was not detected except with the reference Bt kurstaki HD-1 strain. Bioassays against Aedes caspuis and Culex pipiens larvae indicated that 11 strains displayed better larvicidal activity compared with Bacillus thuringiensis H14 (Bti) reference (LC50 0.6 μg/ml) strain against Ae. caspuis, but only two strains (620A & 633R1, LC50 of 0.09 μg/ml & 0.064 μg/ml) that gave significant enhancement. Additionally, one strain (633R1) showed LC50 similar to that of Bti H14 (LC50 0.064 μg/ml) against Cx. pipiens. With the exception of cyt primers, sequenced DNA of all positive primers amplicons revealed 95 to 99% identity in GenBank with Bacillus thuringiensis subsp. israelensis plasmid pBtoxis and also correlated with its SDS-PAGE expressed protein profiles analysis. It is hoped that our wild bio-insecticide Bt strains can be explored in future in the control of mosquitovector borne diseases in Saudi Arabia.

Clinical outcomes for Saudi and Egyptian patients receiving deceased donor liver transplantation in China.

Long waiting list times in liver transplant programs in Saudi Arabia and unavailability of deceased donor transplantation in Egypt have led several patients to seek transplantation in China. All patients who received transplants in China and followed in three centers from January 2003-January 2007 were included. All patients' charts were reviewed. Mortality and morbidity were compared to those transplanted in King Faisal Specialist Hospital & Research Centre (KFSH&RC) during the same period. Seventy-four adult patients were included (46 Saudi nationals; 28 Egyptians). One-year and 3-year cumulative patient survival rates were 83% and 62%, respectively compared to 92% and 84% in KFSH&RC. One-year and 3-year cumulative graft survival rates were 81% and 59%, respectively compared to 90% and 84% in KFSH&RC. Compared to KFSH&RC, the incidence of complications was significantly higher especially biliary complications, sepsis, metastasis and acquired HBV infection posttransplant. Requirements of postoperative interventions and hospital admissions were also significantly greater. Our data show high mortality and morbidity rates in Saudi and Egyptian patients receiving transplants in China. This could be related to more liberal selection criteria, use of donation after cardiac death (DCD) donors or possibly more limited posttransplant care.

Donor outcome after living liver donation: a single-center experience.

OBJECTIVES: To objectively evaluate outcomes after living donor hepatectomy. PATIENTS AND METHOD: Between November 2002 and August 2006, a total of 44 procedures were performed (35 right, eight left, and one aborted after surgical incision). The Clavien classification was used to record surgical complications as follows: grade I, alterations from the ideal postoperative course not requiring specialized pharmacological or surgical treatment; grade II, complications requiring specialized pharmacological treatment, blood transfusion, or total parental nutrition; grade III-a, complications requiring invasive intervention without general anesthesia; Grade III-b, requires general anesthesia; Grade IV-a, single organ dysfunction; Grade IV-b, multiorgan dysfunction; grade V, death; The suffix "d" indicated disability. In this study, grades I and II complications were considered minor, while grades III and V and any lasting disability, serious complications. RESULTS: Male/female ratio was 34/10; median age was 25 years (range, 18 to 42); median hospital stay was 6 days (range, 4 to 14); and only two donors required intraoperative blood transfusion. After a median follow-up of 529 days (range, 8 to 1354), a total of 28 morbidities were encountered in 17 donors (38.6%), including nine donors (20.4%) who had serious complications. Among the 28 donor morbidities, 18 were grade I complications; three were grade III-a complications; five were grade III-b complications; and two were grade IV-a complications. No death was encountered in our experience. CONCLUSIONS: In our experience, donor hepatectomy was not an entirely safe procedure; therefore, extreme care should always be given by the transplant teams to living donors to avoid any distressing morbidity or even, the less likely but more catastrophic, mortality.

Liver transplantation for autoimmune hepatitis: a single-center experience.

OBJECTIVE: To present our experience with deceased donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT) for autoimmune hepatitis (AIH). PATIENTS AND METHOD: Between April 2001 and November 2006, a total of 116 LT procedures were performed (73 DDLTs and 43 LDLTs) in 112 patients (4 retransplants). Of the 112 recipients, 16 patients (14.3%) were transplanted for AIH (15 DDLTs and 1 LDLT). All recipients received FK506- and steroid-based immunosuppressive regimens. RESULTS: The male/female ratio was 3/13, median age was 22 years (range, 15 to 35), and the median MELD score was 25 (range, 11 to 40). Arterial reconstruction was needed in four DDLTs due to severe steroid-induced angiopathy. After a median follow-up period of 530 days (range, 11 to 2016), the overall patient and graft survival rates were 93.8%. Only one patient died following LDLT due to primary graft nonfunction. Histopathologic recurrence was seen in three patients (18.7%) and was successfully treated by optimizing immunosuppression. Markedly elevated serum CA19-9 levels (median, 1069; range, 217 to 2855) was seen in four patients (28%), malignancy was ruled out and all patients normalized serum CA19-9 levels within the first 3 months posttransplant. Steroids withdrawal failed in all recipients and was always accompanied with almost immediate elevation of liver enzymes. CONCLUSIONS: In our experience, LT for AIH shows excellent long-term outcomes, patients are usually young women who present with acute deterioration and high MELD scores, and usually require long-term steroids to prevent rejection and disease recurrence. Some patients have markedly high CA19-9 in absence of malignancy. Some patients also have severe steroid-induced hepatic artery angiopathy necessitating arterial reconstruction during the transplant surgery.

Penile involvement in pityriasis versicolor.

Pityriasis versicolor is a superficial fungal infection of the skin caused by Malassezia furfur (Pityrosporum orbiculare) which is a part of the normal flora of the human skin. The factors which govern the pathogenic conversion of this fungus are not fully understood but a hot humid environment is considered to be a predisposing factor and the disease is very common in tropical countries. Clinically the disease is characterized by scaly hypo- or hyperpigmented macular lesions that are typically located in the trunk, neck and upper arms. The penis is rarely affected. In this report a patient of pityriasis versicolor with involvement of the shaft of the penis is presented.

Disseminated bipolaris infection in an asthmatic patient: case report.

We present the case of a patient with a history of asthma who developed cough and hemoptysis that were unresponsive to antituberculous therapy. Chest roentgenography demonstrated right-sided collapse with consolidation and a pleural effusion. Bronchial biopsy revealed fungal hyphae, and cultures later yielded Bipolaris spicifera. In addition, weight loss and intractable hypotension in association with hyponatremia and elevated potassium levels suggested addisonian crisis, which was confirmed by measurement of serum ACTH and cortisol levels. Computed tomography of the abdomen revealed bilateral adrenal involvement. Tissue obtained on biopsy of the adrenal glands yielded B. spicifera. The patient responded to treatment with 2 g of iv amphotericin B; the adrenal masses and pneumonia resolved, and he remained well until last seen in July 1992. However, he requires replacement therapy with prednisone and fludrocortisone. On review of the available literature, we were unable to find a previously reported case.

Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia.

Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S-phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti-BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1-10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff-) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3-4+ Diff+ as compared to Diff- (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long-term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation.

In vivo cell cycle characteristics of pediatric leukemia patients.

Following i.v. bromodeoxyuridine infusion, a double-label technique using in vitro tritiated thymidine was used to determine the labeling index (LI), duration of S-phase (Ts), and cell cycle time (Tc) in pediatric leukemia patients. Eleven patients with acute lymphoblastic leukemia (ALL) and six patients with acute nonlymphoblastic leukemia (ANLL) were studied. Results of cell cycle kinetic studies are given for each group. Although median values for AML and ALL patients are similar to values reported in previous studies, there is a wide range of values among individual patients. The variation among the kinetic properties of blast cells in these patients reflects the heterogeneity of the acute leukemias of childhood. Further studies will be done to determine if these parameters correlate with outcome of therapy for pediatric leukemia patients.

Eating style and eating behaviour in adolescents.

The relationship between eating style, attitudes towards food and food intake was investigated in 846 British adolescent schoolchildren. Eating style was assessed with the Dutch Eating Behaviour Questionnaire, attitudes towards food with a series of specially prepared questions, and food intake with a diet history taken by a dietitian. The results showed that restraint, external and emotional eating were associated with very different profiles of attitudes and behaviour. Restrained subjects had a higher body weight, more negative attitudes towards food, a lower likelihood of overeating and a lower overall energy intake. External eaters had a lower body weight, positive attitudes to food, and reported a higher energy intake. Emotional eaters fell in between in some ways, with some signs of situational loss of control combined with a negative attitude towards overeating. While external eating appeared to be attenuated by restraint, emotional eating was enhanced by it. The implications of these eating styles for later patterns of eating and weight are discussed.

High expression of transforming growth factor-beta long cell cycle times and a unique clustering of S-phase cells in patients with acute promyelocytic leukemia.

Expression of transforming growth factor-beta (TGF-beta), which inhibits the proliferation of hematopoietic progenitors, was investigated simultaneously with cell cycle characteristics in 63 bone marrow biopsies from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine (BrdU) was administered to every patient (17 newly diagnosed) for determination of the labeling index (LI) and the durations of S-phase (Ts) and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1% v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when compared with other French-American-British subtypes. TGF-beta expression (detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically high, especially in interstitial areas of the biopsies. S-phase cells were found as geographically restricted islands of proliferation (GRIPs) in 20 of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of 15. We conclude that the presence of high TGF-beta expression may explain the biologic basis for the slowly cycling nature of leukemic promyelocytes in APL as well as the unique clustering of S-phase cells observed in GRIPs.

In situ cell cycle kinetics in bone marrow biopsies following sequential infusions of IUdR/BrdU in patients with hematopoietic malignancies.

Examination of the proliferative characteristics of myeloblasts was undertaken in situ in bone marrow (BM) biopsies of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following sequential infusions of iodo- (IUdR) and bromodeoxyuridine (BrdU). The ability to identify S-phase cells which have incorporated both or either one of the labels in vivo by using two monoclonal antibodies in vitro permitted the measurement of labeling index (LI) and durations of S-phase (Ts) and the total cell cycle (Tc) both from the BM aspirates and biopsies. While the LI is 2-3 times higher in biopsies, Ts and Tc are fairly comparable in the two samples in 8/10 cases (p = 0.02 and 0.003 respectively). Advantages associated with the determination of cell cycle parameters in BM biopsies have been discussed at length.

Cell cycle parameters and DNA ploidy in colorectal carcinomas.

Seven patients with colorectal adenocarcinoma and one with squamous cell carcinoma of anorectal region were infused preoperatively with iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU) in sequence (100 mg/m2 x 1 hr each with 1-hr interval in between) to label S-phase cells. The tumor biopsy specimens were embedded in glycol-methacrylate and 2-microns thick sections were treated with two monoclonal antibodies which permitted the identification of cells which incorporated IUdR only, BrdU only, both IUdR and BrdU, or neither IUdR or BrdU. The labeling index of tumors varied from 17.3 to 35.6% (mean = 25.78 +/- 6.162), duration of S-phase ranged from 14.0 to 23.9 hr (mean = 18.73 +/- 3.712), and total cell cycle time ranged from 39.4 to 123.4 hr (mean = 76.78 +/- 24.165). The architecture of the tumor was well preserved and a variable number of DNA synthesizing mononuclear cells were identified within and around the tumor. Image analysis of Feulgen-stained smears of the tumors was done to measure the DNA content of seven tumor samples. Each tumor was found to be hyperdiploid with multiple modal values. The studies described here demonstrate the feasibility of performing cell cycle kinetic measurements on gastrointestinal tumors which have been labeled in vivo. The ability to perform these measurements on tumor biopsies allows the avoidance of artifacts introduced when solid tumors are disaggregated in vitro for study.

Simultaneous immunohistochemical detection of IUdR and BrdU infused intravenously to cancer patients.

Cell cycle kinetics of solid tumors in the past have been restricted to an in vitro labeling index (LI) measurement. Two thymidine analogues, bromodeoxyuridine (BrdU) and iododeoxyuridine (IUdR), can be used to label S-phase cells in vivo because they can be detected in situ by use of monoclonal antibodies (MAb) against BrdU (Br-3) or IUdR (3D9). Patients with a variety of solid tumors (lymphoma, brain, colon cancers) received sequential intravenous IUdR and BrdU. Tumor tissue removed at the end of infusion was embedded in plastic and treated with MAb Br-3 and 3D9 sequentially, using a modification of a previously described method. Clearly single and double labeled cells were visible, which enabled us to determine the duration of S-phase (Ts) and the total cell cycle time (Tc), in addition to the LI in these tumors. Detailed control experiments using tissue culture cell lines as well as bone marrow cells from leukemic patients are described, including the comparison of this double label technique with our previously described BrdU-tritiated thymidine technique. We conclude that the two methods are comparable and that the IUdR/BrdU method permits rapid and reliable cell cycle measurements in solid tumors.