Vesiculobullous Hailey-Hailey disease: Successful treatment with oral retinoids

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with lowdose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.     

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.     

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.     

Induced drug resistance inhibits selection of initiated cells and cancer development

Compounds exerting a mitoinhibitory effect on normal hepatocytes are potent promoters in the resistant hepatocyte model of chemical carcinogenesis in combination with stimulation of regenerative growth by partial hepatectomy or treatment with carbon tetrachloride. 2- Acetylaminofluorene (2-AAF) almost completely inhibits liver cell regeneration after partial hepatectomy, allowing only resistant cells to participate in regenerative growth. After initiation by diethylnitrosamine and promotion with 2-AAF and partial hepatectomy (PH), focal growth of initiated cells generates liver lesions which occupy 40% of the hepatic volume three weeks after PH. In this work the mechanism for the anti promoting effects of phenobarbital and 3- methylcholantrene were investigated as well as their effects on the development of malignant hepatocellular carcinoma in the resistant hepatocyte model. Treatment with phenobarbital or, especially, 3- methylcholanthrene rendered normal rat hepatocytes resistant to the mitoinhibitory effect of 2-AAF. In combination with 2-AAF/PH, 3- methylcholanthrene shortened the regenerative growth period to less than one week. In the Solt-Farber protocol for experimental hepatocarcinogenesis, treatment with phenobarbital or 3- methylcholanthrene during promotion with 2-AAF/PH permitted hepatocytes surrounding the focal lesions to respond with regenerative growth. The foci and surrounding liver grew until the liver/body mass index reached the control value. With phenobarbital treatment the total focal volume was 20% of the liver volume three weeks after PH, whereas the corresponding value in the case of 3-methylcholanthrene was only 1%. Labelling index data supported the conclusion that growth of the liver lesions in the resistant hepatocyte model was dependent on differential inhibition of normal hepatocyte growth by the promoter and that the size of the foci obtained was related to the length of time after PH required to complete liver regeneration. 3-methylcholanthrene induced 2- AAF resistance prevented the development of large persistent nodules and hepatocellular carcinoma while phenobarbital delayed cancer development with several month. The data thus supports the idea that the degree of clonal expansion during promotion determines the size of the population at risk for malignant transformation, as well as the final frequency of carcinomas.      

常染色体16三体胎鼠和正常同窝鼠肠神经系发育

目的 研究Ｄｏｗｎ综合征动物模型常染色体１６三体胎鼠及其正常同窝鼠肠神经系发育状况。方法 （１）将ＮＭＲ－１雌鼠与携带有两个Ｒｏｂｅｒｔｓｏｎｉａｎ（Ｒｂ）易位（１１,１６）,Ｒｂ（１６,１７）８Ｌｕｂｔ＾ＷＬｕｂ３雄鼠进行交配,繁殖常染色体１６三体胎鼠。（２）采用细胞遗传学分析,以检出两条Ｒｂ染色体和４１条染色体者定为常染色体１６三体胎鼠。（３）采用高度特异的神经标记物蛋白基因产物９．５抗体进行