CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice.

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

Topography-Guided PRK and Crosslinking in Eyes with Keratoconus and Post-LASIK Ectasia.

Topography-guided photorefractive keratectomy (TG-PRK) combined with corneal collagen crosslinking (CXL) has been shown to potentially improve vision and stabilize progression in patients with keratoconus (KC). We attempted to reproduce the previously published results using a different laser platform (AMARIS 500E) in patients with KC and post-LASIK ectasia (PLE). All of the 9 included eyes showed improved topography (Kmax, Kmean, RMS HOA, vertical coma, cylinder; p < 0.05) and improved visual acuity (BCVA, UCVA; p < 0.05) after 18 months. Despite some still uncontrollable factors, the combination of TG-PRK and CXL may be a promising option to regularize and stabilize corneas with KC and PLE and improve visual acuity.

A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family.

BACKGROUND: Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family. METHODS: Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema. RESULTS: We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation. CONCLUSION: The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.

The impact of infectious ocular emergencies on hospital resources.

BACKGROUND: Infectious ocular emergencies cannot be pre-planned, need a more labour-intensive treatment and are often associated with prolonged hospitalisation. The aim of this study is to assess the impact of infectious ocular emergencies on hospital resources and identify changing trends over the last 10 years. PATIENTS AND METHODS: In a retrospective chart review 13,587 inpatient records from 1998 to 2007 were analyzed for the reason for emergency hospitalization, treatment data, length of hospitalizations and economical impact. RESULTS: 341 cases of severe infectious ocular emergencies with the need for emergency hospitalization were identified. The annual incidence of such emergencies increased continuously and has more than doubled during the last 10 years (51 vs. 24 annual cases). Within the same period the average hospitalization time of all non-infectious patients decreased from 5.41 to 4.95 days while inpatient stay due to infectious ocular emergencies decreased from 10.13 to 8.18 days. The average nursing effort was 4.26 hours per day in the infectious group, while electively admitted patients had an average requirement for nursing time of only 2.92 hours per day. CONCLUSION: The increase in infectious-related hospitalizations, their unpredictability and the need for a more intensive treatment regime have an increasing impact on hospital resources.

Femtosecond laser versus manual dissection for top hat penetrating keratoplasty.

AIM: To compare the outcomes of IntraLase-enabled top hat penetrating keratoplasty (IEK) versus retrospective results of manual top hat penetrating keratoplasty (TH-PKP) and conventional PKP. PATIENTS/METHODS: This non-randomised prospective study included 94 eyes: 23 eyes underwent IEK, 36 TH-PKP and 35 conventional PKP. Preoperative and postoperative manifest refraction, uncorrected and best-spectacle corrected visual acuity (BSCVA), high-order ocular aberrations (HOA), endothelial cell counts and complications were analysed. RESULTS: At 12 months of follow-up, the mean log MAR BSCVA was 0.32 (SD 0.31) in the IEK group, 0.53 (0.36) in the TH PKP group (p = 0.03) and 0.39 (0.30) in the conventional PKP group (p = 0.4). The mean spherical equivalent was similar between the groups and was less than -2.2 dioptres. The mean cylinder was similar in the IEK and conventional PKP group (3.6 (1.9) dioptres and 4.1 (1.8) dioptres, respectively), and was significantly lower than the TH-PKP group (5.1 (3.2) dioptres, p = 0.04). The complications rate and high-order ocular aberrations were similar between the three groups studied. The mean endothelial cell loss was significantly lower at 12 months of follow-up in the IEK and the TH-PKP groups versus conventional PKP (32.4% and 22.3% vs 40.8%, respectively) (p = 0.05). The mean time to suture removal was 4.1 (1.2) months in the IEK group and 3.9 (1.5) months in the TH-PKP group versus 9.7 (1.1) months in the conventional PKP group (p<0.0001). CONCLUSIONS: IEK is a safe and stable procedure. It results in higher endothelial counts and faster suture removal in comparison with the conventional PKP, and has less astigmatism and better BSCVA in comparison with the manual TH-PKP.

Vacancy island creation and coalescence using automated scanning tunneling microscopy.

We demonstrate that scanning tunneling microscope tip-surface crash events can be utilized as an efficient means for the creation of predefined island configurations for diffusion studies. Using this method, islands of varying size can be created and placed in close proximity, increasing the probability of initiating and observing coalescence events. Data obtained from crash initiated events on a Ag(111) surface are presented. Relaxation time exponents extracted from these data confirm that our method gives results consistent with previous, sputter-obtained island coalescence studies. We also describe an instrument-control routine developed for these measurements that utilizes commercial imaging and off-the-shelf automation software to automate the tracking of islands or other features by the microscope.

[Juvenile cataract associated with microcornea and glucosuria: a new syndrome]. / Juvenile Katarakt assoziiert mit Mikrokornea und Glukosurie: Ein neues Syndrom.

BACKGROUND: Predisposition is responsible for approximately 50% of age-related cataracts. Investigation of inherited forms of cataract provides the opportunity to identify the genes that may play a role in age-related cataract as well. PATIENTS AND METHODS: We describe the phenotype of a Swiss family with juvenile cataract, associated with microcornea and renal glucosuria. 11 of 17 family members in three generations underwent ophthalmic assessment and urine analysis. Medical records or questionnaires were evaluated in the remaining six cases. RESULTS: Eleven family members had progressive juvenile cataract. Eight affected members available for clinical examination had bilateral microcornea, not associated with microphthalmos. Furthermore, renal glucosuria was demonstrated in six of these persons. The mode of inheritance is autosomal-dominant. CONCLUSIONS: We have defined a new syndrome, consisting of the association of juvenile cataract, microcornea and renal glucosuria. The pattern of inheritance is autosomal-dominant. Genotyping is ongoing.

[Pregnancy and drug abuse]. / Graviditet og misbrug af narkotiske stoffer.

The antenatal care of pregnant women with drug abuse is very complex and costly both in money and in time. The women often live under different circumstances than non-abusing women, and their personal and social resources are often very small. Collaboration between the hospital and the social system is essential in order to obtain a positive outcome of the pregnancy. Retrospective records of pregnancy, outcome and follow-up on 18 morphine-abusing women referred for delivery at Glostrup hospital in Copenhagen county over the three year period 1992-1994 are reported here. The study show the children are born in relatively good condition, although almost all needed postnatal detoxification, since their mothers was not able to stop their drug abuse during pregnancy. The pregnancy was with few complications because of tight antenatal care for these women. The study also shows a need for defining a common goal for the care of these women and their children and binding political commitments in order to obtain this goal.

Folate and neural tube defects. Recommendations from a Danish working group.

A working group was established to evaluate the need for an increased folate intake in Danish women to decrease the risk of neural tube defects (NTDs). NTD are birth defects which include anencephaly, encephalocele and spina bifida. In Denmark the incidence is about 1.4 per 1,000 pregnancies. Folate is a B-vitamin found in most food groups. In case-control studies and randomised studies, a protective effect of folic acid supplements on NTDs has been found. The studies show that a periconceptional folic acid supplement of 360 micrograms to 4 mg daily decreases the recurrence rate of NTDs. Likewise, in the few studies which calculate folate intake from the diet, a lower risk of NTD with higher intake of folate from the diet has been found. The folate intake can be increased by the diet, by folic acid supplements or by fortification of food with folic acid. It is concluded that the incidence of NTDs in Denmark will decrease if the folate intake in fertile women increases. All women planning pregnancy should receive dietary counselling. Women who do not eat according to the Nordic Nutrition Recommendations, and women with an increased risk due to diseases are recommended a supplement of 400 micrograms folic acid daily from a multivitamin/folic acid tablet. Women who have had a child with NTD and women who themselves have NTDs are recommended a supplement of 5 mg folic acid daily. Dietary changes and supplements should be initiated when pregnancy is planned.

[Hysterectomy in a Danish population. Weight-related factors, psychological factors and life style variables]. / Hysterektomi i en dansk befolkning. Voegtrelaterede faktorer, psykologiske faktorer og livsstilsvariabler.

The aim was to assess risk factors for hysterectomy performed for benign conditions. In a prevalence study, 2301 Danish women were selected at random in 1982. Information about weight and slimming history, life-styles, psychological factors, gynaecological history, and social background were obtained. In an incidence study, the cohort was followed from 1982 to 1990 to assess the incidence of hysterectomy. In the prevalence study, weight cycling (recurrent weight loss and weight gain of more than 5 kg) was associated with hysterectomy for benign disease (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.99) independently of overweight, smoking, oral contraceptives, psychological and social factors. In the incidence study, weight cycling was the only significant weight-related risk factor for hysterectomy performed for benign disease (adjusted relative risk 2.49, 95% confidence interval 1.10-5.60), explaining the relation between hysterectomy and psychological factors. Weight cycling might be an important risk factor for premenopausal hysterectomy performed for benign conditions.

Gynaecological correlates of hysterectomy in Danish women.

BACKGROUND: The aim has been to assess the gynaecological characteristics of importance for hysterectomy performed for benign diseases. METHODS: In a prevalence study, 2301 Danish women aged 30, 40, 50, or 60 years, were selected at random in 1982, and self-report questionnaires were collected from 77%. Information about gynaecological and obstetric history, social background, weight and dieting history, and various lifestyles were recorded. Weight and height were measured. In an incidence study, the cohort was followed during 1982-1990 via central registers to assess the incidence of hysterectomy. Logistic and Cox regression were used to analyse data. RESULTS: In the prevalence study, 85% of the hysterectomies were performed for benign conditions. Early menarche (< or = 11 years old) and short-term use of oral contraceptives (OC) (1-4 years) were independent correlates of these hysterectomies by multivariate analyses, whereas multiparity (> or = 4 childbirths) was confounded by education and weight-related factors. Long-term use of OC was associated with lower prevalence of hysterectomy. In the incidence study, short-term use of OC and ever use of progestogen-only minipills were independent risk factors for hysterectomy performed recently for benign diseases in women under 50 in the multivariate analyses. Abortions did not reach significance, and neither multiparity, long-term use of OC, nor early menarche were important. CONCLUSION: The most important gynaecological characteristics related to premenopausal hysterectomy performed for benign diseases are hormonal contraceptives. These findings imply that the decision-making process concerning hysterectomy might depend on women's choice of contraception and compliance with OC as medical treatment.