Cholecystitis: association between ultrasound findings and surgical outcomes.

AIM: To identify sonographic signs of cholecystitis that correlate with surgical outcomes. MATERIALS AND METHODS: Three hundred and thirty-three consecutive patients who underwent cholecystectomy between 22/06/2014 and 1/3/2016 and underwent abdominal ultrasound (US) within 7 days of surgery were included. Individual US signs, including gallstones, gallbladder distention, wall thickening, pericholecystic fluid, and abscess, were graded by two radiologists, 1 and 2. Outcomes included operative duration (OD), drain placement, partial cholecystectomy, conversion from laparoscopic to open cholecystectomy, surgical pathology, bile leak, infection, and 30-day readmission. US signs and outcomes were analysed using analysis of variance, chi-square test, or odds ratios (OR). RESULTS: Radiologist 1 reported 141/333 and radiologist 2 reported 128/333 patients showed gallbladder distention. For the subset with OD, radiologist 1 reported 140/320 and radiologist 2 reported 126/320 patients showed gallbladder distention. Distention was predictive of increased OD (radiologist 1, +23.2 minutes, p<0.0001; radiologist 2, +19.4 minutes, p=0.0003). Cases with gallbladder distention were more likely to have surgical drain placement (OR= 2.60; 95% confidence interval [CI]: 1.12-6.08, p=0.027 radiologist 1; OR=2.59; 95% CI: 1.13-5.95, p=0.025 radiologist 2). Wall thickening was present in 126/333 patients reported by radiologist 1 and 120/333 by radiologist 2. Cases with wall thickening were more likely to have drain placement (OR=2.66; 95% CI: 1.16-6.13, p=0.021 radiologist 1; OR=3.49; 95% CI: 1.49-8.16, p=0.004 radiologist 2). For the subset with OD, wall thickening was present for 121/320 reported by radiologist 1 and 116/320 by radiologist 2 and predicted longer OD (radiologist 1, +15.9 minutes, p=0.0033; radiologist 2, +13.3 minutes, p=0.0143). CONCLUSION: Gallbladder distention and wall thickening on US correlate with prolonged OD and surgical drain placement in patients with cholecystitis.

Evaluation of bioherbicidal potential of Carica papaya leaves / Avaliação do potencial de bioherbicida dase folhas de Carica papaya

Abstract Due to increased number of herbicide resistant weeds, it is needed to explore the allelopathic potential of plants as an alternative. The research was conducted to investigate allelopathic effects of Carica papaya L. leaf powder and aqueous extract on seeds as well as pre-germinated seeds of Avena fatua L., Helianthus annuus L., Rumex dentatus L., Zea mays L. and Triticum aestivum L. on filter paper and soil in Weed Management Program Laboratory, Department of Plant and Environmental Protection at PARC Institute of Advanced Studies in Agriculture, National Agriculture Research Centre, Islamabad, Pakistan. Germination percentage (%), radicle length (cm) and plumule length (cm) were parameters observed for 'Plant leaf powder bioassay' and 'Aqueous extract method'. Most significant growth inhibition was observed in A. fatua seedlings in filter paper method. A. fatua radicle length was reduced by C. papaya aqueous extract (80%) and leaf powder (89%) bioassays. Plumule length was reduced under the influence of aqueous extract (57-73%) and powdered material (59-77%). The inhibitory effects on other test species were in sequence of H. annuus followed by Z. mays and R. dentatus. The aqueous extract showed non-significant effect on wheat seed germination, radicle and plumule growth. It is suggested that C. papaya aqueous extract can be used as source of weed management in wheat crop.

Resumo Devido ao aumento do número de ervas daninhas resistentes aos herbicidas, é necessário explorar o potencial alelopático das plantas como uma alternativa. A pesquisa foi conduzida com o objetivo de investigar os efeitos alelopáticos do pó foliar de Carica papaya e do extrato aquoso das sementes, bem como das sementes pré-germinadas de Avena fatua, Helianthus annuus, Rumex dentatus, Zea mays e Triticum aestivum em papel de filtro e solo no Laboratório do Programa de Manejo de Ervas Daninhas, Departamento de Plantas e Proteção Ambiental do Instituto PARC de Estudos Avançados em Agricultura, Centro Nacional de Pesquisa Agrícola, Islamabad, Paquistão. A porcentagem de germinação (%), o comprimento radicular e o comprimento da plúmula (cm) foram os parâmetros observados para o 'Bioensaio de Pó de Folha de Planta' e o 'Método de Extração Aquoso'. A maior inibição do crescimento foi observada em mudas de A. fatua no método de papel de filtro. O comprimento radicular de A. fatua foi reduzido com os extratos aquosos de C. papaya (80%) e pó de folhas (89%). O comprimento das plúmulas foi reduzido sob a influência do extrato aquoso (57-73%) e material em pó (59-77%). Os efeitos inibitórios em outras espécies-teste foram na sequência de H. annuus seguido por Z. mays e R. dentatus. O extrato aquoso apresentou efeito não significativo na germinação das sementes de trigo, nos crescimentos radiculares e das plúmulas. Sugere-se que o extrato aquoso de C. papaya pode ser utilizado como fonte de manejo de plantas daninhas na cultura do trigo.

Evaluation of bioherbicidal potential of Carica papaya leaves.

Due to increased number of herbicide resistant weeds, it is needed to explore the allelopathic potential of plants as an alternative. The research was conducted to investigate allelopathic effects of Carica papaya L. leaf powder and aqueous extract on seeds as well as pre-germinated seeds of Avena fatua L., Helianthus annuus L., Rumex dentatus L., Zea mays L. and Triticum aestivum L. on filter paper and soil in Weed Management Program Laboratory, Department of Plant and Environmental Protection at PARC Institute of Advanced Studies in Agriculture, National Agriculture Research Centre, Islamabad, Pakistan. Germination percentage (%), radicle length (cm) and plumule length (cm) were parameters observed for 'Plant leaf powder bioassay' and 'Aqueous extract method'. Most significant growth inhibition was observed in A. fatua seedlings in filter paper method. A. fatua radicle length was reduced by C. papaya aqueous extract (80%) and leaf powder (89%) bioassays. Plumule length was reduced under the influence of aqueous extract (57-73%) and powdered material (59-77%). The inhibitory effects on other test species were in sequence of H. annuus followed by Z. mays and R. dentatus. The aqueous extract showed non-significant effect on wheat seed germination, radicle and plumule growth. It is suggested that C. papaya aqueous extract can be used as source of weed management in wheat crop.

Etiology-Specific Mineralization Patterns in Patients with Labyrinthitis Ossificans.

BACKGROUND AND PURPOSE: Our aim was to identify whether specific patterns of ossification in labyrinthitis ossificans are associated with the known risk factors. Labyrinthitis ossificans has been described as sequela of prior temporal bone trauma, prior infection, and other disorders including sickle cell disease. Specific patterns of mineralization in the membranous labyrinth associated with these risk factors has not been previously described. MATERIALS AND METHODS: This was a retrospective study evaluating temporal bone CT scans at our institution from November 2005 to May 2018 in patients with labyrinthitis ossificans. Membranous labyrinthine structures evaluated for ossification included the following: basal, middle, and apical cochlear turns; lateral, posterior, and superior semicircular canals; and the vestibule for both ears in all patients. These structures were assigned a severity score, 0-4, based on degree of mineralization. Clinical records were reviewed for potential labyrinthitis ossificans risk factors. Basic descriptive statistics and a mixed model were used to correlate the degree and patterns of ossification with clinical history. RESULTS: Forty-four patients (58 ears) with labyrinthitis ossificans were identified and evaluated. The most common risk factors were chronic otomastoiditis (n = 18), temporal bone surgery (n = 9), temporal bone trauma (n = 6), sickle cell disease (n = 5), and meningitis (n = 4). For all etiologies, the semicircular canals were most severely affected, and the vestibule was the least. In patients with prior temporal bone surgery, significantly greater mineralization was seen in the basal turn of the cochlea (P = .027), the vestibule (P = .001), and semicircular canals (P < .001-.008). No significant pattern was identified in patients with meningitis, sickle cell disease, or trauma. CONCLUSIONS: Significant patterns of mineralization in labyrinthitis ossificans were observed in patients with prior temporal bone surgery. For all etiologies, the semicircular canals were most severely affected. No significant mineralization pattern was observed in patients with chronic otomastoiditis, meningitis, sickle cell disease, or prior temporal bone trauma.

CT Texture Analysis of Cervical Lymph Nodes on Contrast-Enhanced [18F] FDG-PET/CT Images to Differentiate Nodal Metastases from Reactive Lymphadenopathy in HIV-Positive Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: Differentiating nodal metastases from reactive adenopathy in HIV-infected patients with [18F] FDG-PET/CT can be challenging because lymph nodes in HIV-positive patients often show increased [18F] FDG uptake. The purpose of this study was to assess CT textural analysis characteristics of HIV-positive and HIV-negative lymph nodes on [18F] FDG-PET/CT to differentiate nodal metastases from disease-specific nodal reactivity. MATERIALS AND METHODS: Nine HIV-positive patients with head and neck squamous cell carcinoma (7 men, 2 women; 29-62 years of age; median age, 48 years) with 22 lymph nodes (≥1 cm) who underwent contrast-enhanced CT with [18F] FDG-PET followed by pathologic evaluation of cervical lymph nodes were retrospectively reviewed. Twenty-six HIV-negative patients with head and neck squamous cell carcinoma with 61 lymph nodes were evaluated as a control group. Each lymph node was manually segmented, and an in-house-developed Matlab-based texture analysis program extracted 41 texture features from each segmented volume. A mixed linear regression model was used to compare the pathologically proved malignant lymph nodes with benign nodes in the 2 enrolled groups. RESULTS: Thirteen (59%) lymph nodes in the HIV-positive group and 22 (36%) lymph nodes in the HIV-negative control group were confirmed as positive for metastases. There were 7 histogram features (P = .017-0.032), 3 gray-level co-occurrence features (P = .009-.025), and 9 gray-level run-length features (P < .001-.033) that demonstrated a significant difference in HIV-positive patients with either benign or malignant lymph nodes. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method of obtaining additional quantitative information to differentiate nodal metastases from disease-specific nodal reactivity in HIV-positive patients with head and neck squamous cell carcinoma.

CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy.

BACKGROUND AND PURPOSE: The accurate prediction of prognosis and failure is crucial for optimizing treatment strategies for patients with cancer. The purpose of this study was to assess the performance of pretreatment CT texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma treated with chemoradiotherapy. MATERIALS AND METHODS: This retrospective study included 62 patients diagnosed with primary head and neck squamous cell carcinoma who underwent contrast-enhanced CT examinations for staging, followed by chemoradiotherapy. CT texture features of the whole primary tumor were measured using an in-house developed Matlab-based texture analysis program. Histogram, gray-level co-occurrence matrix, gray-level run-length, gray-level gradient matrix, and Laws features were used for texture feature extraction. Receiver operating characteristic analysis was used to identify the optimal threshold of any significant texture parameter. We used multivariate Cox proportional hazards models to examine the association between the CT texture parameter and local failure, adjusting for age, sex, smoking, primary tumor stage, primary tumor volume, and human papillomavirus status. RESULTS: Twenty-two patients (35.5%) developed local failure, and the remaining 40 (64.5%) showed local control. Multivariate analysis revealed that 3 histogram features (geometric mean [hazard ratio = 4.68, P = .026], harmonic mean [hazard ratio = 8.61, P = .004], and fourth moment [hazard ratio = 4.56, P = .048]) and 4 gray-level run-length features (short-run emphasis [hazard ratio = 3.75, P = .044], gray-level nonuniformity [hazard ratio = 5.72, P = .004], run-length nonuniformity [hazard ratio = 4.15, P = .043], and short-run low gray-level emphasis [hazard ratio = 5.94, P = .035]) were significant predictors of outcome after adjusting for clinical variables. CONCLUSIONS: Independent primary tumor CT texture analysis parameters are associated with local failure in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.

Quantitative Assessment of Variation in CT Parameters on Texture Features: Pilot Study Using a Nonanatomic Phantom.

Our aim was to evaluate changes in texture features based on variations in CT parameters on a phantom. Scans were performed with varying milliampere, kilovolt, section thickness, pitch, and acquisition mode. Forty-two texture features were extracted by using an in-house-developed Matlab program. Two-tailed t tests and false-detection analyses were performed with significant differences in texture features based on detector array configurations (Q values = 0.001-0.006), section thickness (Q values = 0.0002-0.001), and acquisition mode (Q values = 0.003-0.006). Variations in milliampere and kilovolt had no significant effect.

Evaluation of bioherbicidal potential of Carica papaya leaves

Abstract Due to increased number of herbicide resistant weeds, it is needed to explore the allelopathic potential of plants as an alternative. The research was conducted to investigate allelopathic effects of Carica papaya L. leaf powder and aqueous extract on seeds as well as pre-germinated seeds of Avena fatua L., Helianthus annuus L., Rumex dentatus L., Zea mays L. and Triticum aestivum L. on filter paper and soil in Weed Management Program Laboratory, Department of Plant and Environmental Protection at PARC Institute of Advanced Studies in Agriculture, National Agriculture Research Centre, Islamabad, Pakistan. Germination percentage (%), radicle length (cm) and plumule length (cm) were parameters observed for Plant leaf powder bioassay and Aqueous extract method. Most significant growth inhibition was observed in A. fatua seedlings in filter paper method. A. fatua radicle length was reduced by C. papaya aqueous extract (80%) and leaf powder (89%) bioassays. Plumule length was reduced under the influence of aqueous extract (57-73%) and powdered material (59-77%). The inhibitory effects on other test species were in sequence of H. annuus followed by Z. mays and R. dentatus. The aqueous extract showed non-significant effect on wheat seed germination, radicle and plumule growth. It is suggested that C. papaya aqueous extract can be used as source of weed management in wheat crop.

Resumo Devido ao aumento do número de ervas daninhas resistentes aos herbicidas, é necessário explorar o potencial alelopático das plantas como uma alternativa. A pesquisa foi conduzida com o objetivo de investigar os efeitos alelopáticos do pó foliar de Carica papaya e do extrato aquoso das sementes, bem como das sementes pré-germinadas de Avena fatua, Helianthus annuus, Rumex dentatus, Zea mays e Triticum aestivum em papel de filtro e solo no Laboratório do Programa de Manejo de Ervas Daninhas, Departamento de Plantas e Proteção Ambiental do Instituto PARC de Estudos Avançados em Agricultura, Centro Nacional de Pesquisa Agrícola, Islamabad, Paquistão. A porcentagem de germinação (%), o comprimento radicular e o comprimento da plúmula (cm) foram os parâmetros observados para o 'Bioensaio de Pó de Folha de Planta' e o 'Método de Extração Aquoso'. A maior inibição do crescimento foi observada em mudas de A. fatua no método de papel de filtro. O comprimento radicular de A. fatua foi reduzido com os extratos aquosos de C. papaya (80%) e pó de folhas (89%). O comprimento das plúmulas foi reduzido sob a influência do extrato aquoso (57-73%) e material em pó (59-77%). Os efeitos inibitórios em outras espécies-teste foram na sequência de H. annuus seguido por Z. mays e R. dentatus. O extrato aquoso apresentou efeito não significativo na germinação das sementes de trigo, nos crescimentos radiculares e das plúmulas. Sugere-se que o extrato aquoso de C. papaya pode ser utilizado como fonte de manejo de plantas daninhas na cultura do trigo.

Using Texture Analysis to Determine Human Papillomavirus Status of Oropharyngeal Squamous Cell Carcinomas on CT.

BACKGROUND AND PURPOSE: Human papillomavirus-associated oropharyngeal squamous cell carcinoma is increasing in prevalence and typically occurs in younger patients than human papillomavirus-negative squamous cell carcinoma. While imaging features of human papillomavirus-positive versus human papillomavirus-negative squamous cell carcinoma nodal metastases have been described, characteristics distinguishing human papillomavirus-positive from human papillomavirus-negative primary squamous cell carcinomas have not been well established. The purpose of this project was to evaluate the use of texture features to distinguish human papillomavirus-positive and human papillomavirus-negative primary oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Following institutional review board approval, 40 patients with primary oropharyngeal squamous cell carcinoma and known human papillomavirus status who underwent contrast-enhanced CT between December 2009 and October 2013 were included in this study. Segmentation of the primary lesion was manually performed with a semiautomated graphical-user interface. Following segmentation, an in-house-developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences in texture parameters between human papillomavirus-positive and human papillomavirus-negative squamous cell carcinomas. RESULTS: Of the 40 included patients, 29 had human papillomavirus-positive oropharyngeal squamous cell carcinoma and 11 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. Significant differences were seen in the histogram parameters median (P = .006) and entropy (P = .016) and squamous cell carcinoma entropy (P = .043). CONCLUSIONS: There are statistically significant differences in some texture features between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors. Texture analysis may be considered an adjunct to the evaluation of human papillomavirus status and characterization of squamous cell carcinoma.

Prediction of locoregional control in head and neck squamous cell carcinoma with serial CT perfusion during radiotherapy.

BACKGROUND AND PURPOSE: Tumor hypoxia is a known factor of radioresistance in HNSCC. CTP is a noninvasive method of measuring tumor perfusion in vivo. The purpose of our study was to determine serial changes in tumor perfusion in HNSCC during a course of RT by using CTP and to correlate tumor perfusion measurements to LRC. MATERIALS AND METHODS: A prospective study was performed in 15 patients with HNSCC receiving definitive RT who underwent serial CTP before RT; at weeks 2, 4, and 6 of RT; and 6 weeks after RT. The median follow-up was 28 months (range, 6-44 months). Thirteen patients achieved LRC, and 2 patients had LRF. Tumor perfusion parameters, including BF, BV, MTT, and CP, were obtained by using a deconvolution-based analysis. RESULTS: Pretreatment tumor BF was significantly higher in patients who achieved LRC, 118.0 mL/100 g/min, compared with those with LRF, 53.4 mL/100 g/min (P = .004). Similarly, pretreatment CP was higher in patients with LRC, 16.6 mL/100 g/min, compared with those with LRF, 7.7 mL/100 g/min (P = .02). At week 2 of RT, tumor BF parameters showed a 27.5% increase versus an 18.1% decrease from pretreatment BF values (P = .046) in patients with LRC and LRF, respectively. A decrease in BF and BV was observed in both groups 6 weeks after RT compared with these values at baseline scanning. CONCLUSIONS: An increase in tumor BF and CP by using CTP early during a course of RT predicts LRC in patients with HNSCC treated with RT.

Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease.

BACKGROUND: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology. METHODS: We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory. RESULTS: The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05). CONCLUSION: Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.

Schistosoma mansoni of the conus medularis: case report.

A six year old girl was admitted to the Kenyatta National Hospital paediatric unit with history of headaches, fever, neck stiffness and paraesthesias of the lower limbs. She was empirically commenced on antimeningitic treatment. Her neurological state deteriorated over a period of two months to paraparesis and paraplegia of the lower limbs with urinary and stool incontinence. A neurology review revealed a sensory level at T10 with power grade 2 in the lower limbs. A myelogram revealed a block of contrast at T12. An impression of cord compression by an intraspinal tumour was made. Laminectomy and posterior midline myelotomy was performed. At operation a greyish-white intramedullary mass lesion was found. Histology revealed a schistosoma mansoni ovum surrounded by granulomatous tissue with giant cells and polymorphoneuclear leucocytes. The child was commenced on paziquantel 1000 mg and dexamethasone 24 mg per day in divided doses. There was marked neurological improvement and the patient went home one month later. She was able to walk without support and was continent of urine and stool at the time of discharge.

Proto-oncogene ras GTPase-linked induction of glutathione-S-transferase by growth factors in PC12 cells.

This report provides evidence linking activation of Ras GTPase by growth factors and induction of glutathione-S-transferase isozymes in PC12 cells. Ras GTPase was activated by EGF, NGF, insulin and phorbolester in PC12 cells. Activation of Ras GTPase was found to be associated with induction of the expression of GST mu and pi isoenzymes while there was no detectable induction of GST alpha expression. GST pi was found to be induced by all the Ras GTPase activating agents tested while activation of Ras by phorbolester and insulin induced expression of GST mu only. These results suggest a role of Ras, at least in part, in controlling the expression of GST and that there might be independent signalling pathways for the expression of different GST isoenzymes. GST activity was found to be very high (4-fold) in the lysate obtained from retinoic acid treated PC12 cells when compared with untreated cells. Induction of GST expression was found to be initiated within 30 min of retinoic acid treatment in PC12 cells reaching a maximum level at 4 h. However, immunoblot analysis showed that retinoic acid (RA), unlike mitogens/growth factors, weakly induced the expression of GST pi but not the expression of alpha, mu and microsomal GSTs. Overxpression of inhibitory polypeptides that block signals generated from Ras and Cdc42 was found to reverse the retinoic acid activation-dependent induction of GST expression in PC12 cells. These results provide evidence for the first time suggesting a novel role of Ras GTPase in the regulation of GST expression which might have a significant implication in developing drug resistance and/or growth of cancer cells.

A novel enantioselective synthesis of (S)-(-)- and (R)-(+)-nornicotine via alkylation of a chiral 2-hydroxy-3-pinanone ketimine template.

An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with moderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R-(+)- or 1S,2S,5S-(-)-2-hydroxy-3-pinanone and 3-(aminomethyl)pyridine with 3-bromopropan-1-ol. After cleavage of the respective C-alkylated ketimines with NH2OH.HCl, and treatment of the resulting amino alcohols with HBr, followed by base-catalyzed intramolecular ring closure, (S)-(-)-nornicotine and (R)-(+)-nornicotine were obtained with ee values of 91% and 81%, respectively.

The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family.

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma+-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma+-thalassemia is responsible for neonatal hemolytic anemia in this family.

The CDC42-specific inhibitor derived from ACK-1 blocks v-Ha-Ras-induced transformation.

Based on the previous experiments with the N17 mutant of CDC42, it has been speculated, but not proved as yet, that CDC42 is required for Ras-induced malignant transformation of fibroblasts. However, since this inhibitor could sequester many GDP-dissociation stimulators (GDSs), such as DBL, OST and Tiam-1 which activate not only CDC42, but also Rho or Rac, in fact it is not a specific inhibitor that inactivates only CDC42. Thus, we have taken the minimum CDC42-binding domain (residues 504 - 545, called ACK42) of the Tyr-kinase ACK-1 that binds only CDC42 in the GTP-bound form, and thereby blocking the interactions of CDC42-GTP with its downstream effectors such as ACKs, PAKs and N-WASP. First of all, using the ACK42-GST fusion protein as a specific ligand for the GTP-CDC42 complex, we have revealed that CDC42 is activated by oncogenic Ras mutants such as v-Ha-Ras in NIH3T3 fibroblasts, and similarly in PC12 cells by both NGF (Nerve Growth Factor) and EGF (Epidermal Growth Factor) which activate the endogenous normal Ras, providing the first direct evidence that CDC42 acts downstream of Ras and NGF/EGF. Furthermore, over-expression of ACK42 completely reversed Ras-induced malignant phenotypes such as focus formation and anchorage/serum-independent growth of the fibroblasts, and a cell-permeable derivative of ACK42 called WR-ACK42 strongly inhibited the growth of Ras transformants, with little effect on the parental normal cell growth, and also abolished Ras-induced filopodium/microspike formation of the fibroblasts which is CDC42-dependent. These observations unambiguously proved for the first time that the RAS-induced activation of CDC42 is indeed essential for Ras to transform the fibroblasts, and furthermore suggest that ACK42 or its peptidomimetics are potentially useful for genotherapy or chemotherapy of Ras-associated cancer.

Epidemiology of clinical hyperbilirubinaemia in Al Ain, United Arab Emirates.

All infants born at Al Ain Hospital, United Arab Emirates between 1 January and 30 June 1995 who developed clinically relevant hyperbilirubinaemia defined as jaundice requiring investigation and treatment were prospectively studied. Of the 2300 live births, 85 (3.7%) developed hyperbilirubinaemia. Of these, 22 were premature, 22 had ABO haemolytic disease of the newborn, eight had G6PD deficiency (Mediterranean), seven had breast-milk jaundice, five were born to mothers with diabetes mellitus and one had Rh incompatibility. No specific factor was identified in 20 (24%). Significant differences in the distribution of diagnostic categories were found among the major ethnic groups in the population studied. This first study of the epidemiology of clinically relevant hyperbilirubinaemia in this community identified locally relevant risk factors and highlighted areas of health care which, if modified, might reduce the incidence of hyperbilirubinaemia.

PIP: If untreated, severe unconjugated hyperbilirubinemia is neurotoxic. Management of the condition therefore includes preventing serum bilirubin from reaching toxic levels. Identifying infants at risk of developing severe hyperbilirubinemia and early intervention have reduced levels of morbidity and mortality associated with bilirubin encephalopathy. The incidence of neonatal jaundice and the etiological factors associated with hyperbilirubinemia vary by locale. All infants born at Al Ain Hospital, United Arab Emirates, between January 1 and June 30, 1995, who developed clinically relevant hyperbilirubinemia defined as jaundice requiring investigation and treatment were prospectively studied. 85 (3.7%) of the 2300 live births developed hyperbilirubinemia. Of those, 22 were premature, 22 had ABO hemolytic disease of the newborn, 8 had G6PD deficiency (Mediterranean), 7 had breast milk jaundice, 5 were born to mothers with diabetes mellitus, and 1 had Rh incompatibility. No specific factor was identified in 20 (24%) infants. Significant differences in the distribution of diagnostic categories were found among the major ethnic groups in the population studied.

Role of MRI in the diagnosis of cervical brucellar spondylitis: case report.

Magnetic resonance imaging (MRI) is the most suitable modality for evaluation of infectious spondylitis. It is more sensitive than other imaging modalities for detecting presence and extent of such infections. Though it is not always possible to differentiate various infections on the basis of imaging findings alone, there are certain features which along with a good clinical background, can differentiate brucellar spondylitis from other spinal infections. It is useful to follow up such patients after specific chemotherapy to further confirm the diagnosis.