First trimester urinary placental growth factor and development of pre-eclampsia

Objective  To compare urinary placental growth factor (PlGF) concentration at 11⁺⁰ to 13⁺⁶ weeks of gestation in women who subsequently develop pre-eclampsia with normotensive controls.
Design  Nested case–control study within a prospective study for first trimester prediction of pre-eclampsia.
Setting  Routine antenatal visit in a teaching hospital.
Population  Fifty-two women who developed pre-eclampsia and 52 controls matched for gestational age and sample storage time.
Methods  Urinary PlGF concentration and PlGF to creatinine ratio were measured in women who developed pre-eclampsia and their matched controls. Comparisons between groups were performed using Student's t test.
Main outcome measures  Development of pre-eclampsia.
Results  In the pre-eclampsia group, the median urinary PlGF concentration (20.6 pg/ml, interquartile range [IQR] 9.1–32.0 pg/ml) and median urinary PlGF to creatinine ratio (1.6 pg/mg, IQR 1.2–2.5 pg/mg) were not significantly different from the control group (11.8 pg/ml, IQR 5.5–29.8 pg/ml, P = 0.1 and 1.7 pg/mg, IQR 1.2–2.3 pg/mg, P = 0.3, respectively). There were no significant differences between women with early-onset pre-eclampsia requiring delivery before 34 weeks ( n = 13) and those with late-onset pre-eclampsia ( n = 39) and between women with pre-eclampsia and fetal growth restriction (FGR) ( n = 25) and those with pre-eclampsia and no FGR ( n = 27) in either median PlGF concentration or median urinary PlGF to creatinine ratio.
Conclusions  The development of pre-eclampsia is not preceded by altered urinary PlGF concentration in the first trimester of pregnancy.     

Comparison of the morphological transforming activities of dibenzo[a,l]pyrene and benzo[a]pyrene in C3H10T1/2CL8 cells and characterization of the dibenzo[a,l]pyrene-DNA adducts

C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the in vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P). The morphological transforming activities of these rodent carcinogens were compared using replicate concentration- response studies. In concentration ranges where both polycyclic aromatic hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times as potent as B[a]P based on concentration. At lower concentrations DB[a,l]P was active at 0.10 and 0.20 microM, concentrations where B[a]P was inactive. This makes DB[a,l]P the most potent non-methylated PAH evaluated to date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells were analyzed by both TLC and TLC/HPLC 32P-postlabeling methods using mononucleotide 3'-phosphate adduct standards derived from the reactions of anti-DB[a,l]P-11,12-diol- 13,14-epoxide (anti-DB[a,l]PDE) and syn-DB[a,l]P-11,12-diol-13,14- epoxide (syn-DB[a,l]PDE) with deoxyadenosine 3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNA adducts observed in C3H10T1/2 cells treated with DB[a,l]P were identified as being derived from the metabolism of DB[a,l]P to its fjord region diol epoxides through DB[a,l]P-11,12-diol. The predominant adduct was identified as an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti- DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts with minor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adduct data are consistent with similar findings of DB[a,l]PDE- deoxyadenosine adducts in mouse skin studies and human mammary cells in culture.      

Six new cases of CRB2-related syndrome and a review of clinical findings in 28 reported patients

The Crumbs homolog-2 (CRB2)-related syndrome (CRBS-RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha-fetoprotein levels in maternal serum and amniotic fluid. CRB2-related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-RS have highlighted renal disease with persistent proteinuria and steroid-resistant nephrotic syndrome (SRNS). We report six new and review 28 reported patients with pathogenic variants in CRB2. We compare clinical features and variant information in CRB2 in patients with CRB2-RS and in those with isolated renal disease. The kidneys were the most frequently involved body system and 11 patients had only renal manifestations with SRNS or nephrotic syndrome. Central nervous system involvement was the next most common manifestation, followed by cardiac findings that included Scimitar syndrome. There was a significant clustering of pathogenic variants for CRB2-RS in exons 8 and 10, whereas pathogenic variants in exons 12 and 13 were associated with isolated renal disease. Further information is needed to determine optimal management but monitoring for renal and ocular complications should be considered.     

On the maternal transfer of 4-aminobiphenyl in rats

The potential for 4-aminobiphenyl (4-ABP) to be transferredfrom circulating blood into the milk of lactating Sprague—Dawleyrats was determined. The distribution of ¹⁴C-labeled 4-ABP intomilk was examined at time intervals of < 1, 20, 60, 120,240 and 480 min after i.v. dose administration. Eliminationof radioactivity from blood and milk was determined to be biphasic.The levels of 4-ABP and/or metabolites were lower in milk thanin blood at all time points examined. The levels of radioactivitydetected in blood declined less rapidly than in milk. That is,the percent of the dose per ml of blood declined from 0.81–0.45,while the percent of the dose per ml of milk declined from 0.38–0.06during the 8 h time period. The radioactivity present in milkwas partially extractable with ethyl acetate with 43% of theradioactivity being extractable at the earliest time point whileonly 16% was extractable after 8 h. The level of radioactivityassociated with the protein precipitate of the milk samplesincreased from 4–21% within 4 h after treatment. The potentialof 4-ABP or its metabolites to exert a genotoxic effect on newbornpups via maternal transfer was also examined. Dams were treatedon day 1 post partum and then daily with 4-ABP (10 mg/kg) incorn oil or corn oil alone for 2 weeks. Each experimental grouphad four litters of pups each containing 5 pups. Pups were sacrificedat 15 days of age, separated by sex and the levels of 4-ABP:DNA adducts in liver determined using ³²P-postlabeling. DNAadduct profiles were similar between male and female pups withtotal adduct levels of 332 and 338 fmol of adducts/mg of DNA,respectively. These results indicate that the genotoxic effectsof 4-ABP can be transmitted from exposed dams to the nursingoffspring.     

Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki- 67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.     

Dietary fibre, exercise and serum lipids and lipoprotein cholesterols in 12 to 15 year olds

Serum lipid and lipoprotein cholesterol levels track from childhood and are associated with risk of coronary heart disease. There is some evidence that these are influenced by dietary intake and exercise. Serum lipid and lipoprotein cholesterols were measured in a cohort of 119 British children aged 12–15 y who completed a dietary assessment and exercise questionnaire. The ratio of total- to high-density lipoprotein cholesterol fell with increasing fibre intake, but after adjustment for age, body mass index, sex and other dietary factors, this was not statistically significant. Children exercising at least once a day had significantly lower serum total cholesterol and low density lipoprotein cholesterol levels than those exercising less frequently, even after adjustment for the above factors and dietary fibre intake. No dietary factor was significantly associated with any lipid measure after adjustment for the above factors. The challenge is how to optimize exercise level in adolescent children.     

Lineage promiscuity in hemopoietic differentiation and leukemia

An increasing number of reports document instances in which individual leukemic cells coexpress markers normally believed to be restricted to a single lineage. This has been interpreted by McCulloch and colleagues as aberrant programming or lineage infidelity and contrasts with earlier suggestions that lineage fidelity of gene expression was usually maintained in leukemia. We argue that several examples of infidelity are suspect on technical grounds, whereas others are bona fide and require explanation, eg, partial rearrangements and expression of Ig heavy-chain and/or T cell receptor genes in inappropriate cells and terminal deoxynucleotidyl transferase in leukemic myeloblasts. Individual examples of truly aberrant gene expression may well occur in leukemia but with insufficient regularity to be of general significance. We suggest that verifiable and consistent examples of apparent lineage infidelity do not reflect genetic misprogramming but rather the existence of a transient phase of limited promiscuity of gene expression occurring in normal biopotential or multipotential progenitors and able to be preserved as a relic in leukemic blast cell populations that are in maturation arrest. This alternative explanation has interesting implications for mechanisms of hematopoietic differentiation and leads to some testable predictions.     

Colchicine for recurrent pericarditis in children

The incidence of recurrence of acute pericarditis in children varies from 15% to 30% and is accompanied by a high morbidity. Various treatment modalities have been used with variable success rates and side effects. La Serna et al. (Lancet 1987; 26: 1517) were the first to treat adults with recurrent pericarditis with colchicine, and were followed by other authors. To our knowledge no studies in children have been reported. In this paper, we present three children who suffered from viral or idiopathic recurrent pericarditis, despite multiple courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids. They responded remarkably well to colchicine, which was administered for 6 months with no adverse reactions. They continue to do well 18, 11 and 12 months after cessation of treatment, respectively.