Epidemiologic features of hydatidiform mole in the Netherlands

The presented study is a report of epidemiologic data collected between 1978 and 1980 from patients with gestational trophoblastic disease in the Netherlands. Review of curettings from 344 patients with hydatidiform mole and 33 patients with partial mole resulted in review diagnoses of hydatidiform mole in 283 women, of partial mole in 25 women, and of mere hydropic degeneration in 69 women. Upon review of the initial diagnosis of complete and partial hydatidiform mole, 18% of the cases were considered false-positive. After the evacuation of a molar pregnancy, 10% of the patients needed chemotherapy because of the diagnosis of persistent trophoblastic disease. In patients with a review diagnosis of hydropic degeneration, this was never necessary.     

Plasma human chorionic gonadotropin disappearance in hydatidiform mole: a central registry report from the Netherlands

The disappearance time of serum human chorionic gonadotropin (hCG) after the evacuation of hydatidiform mole, partial mole, and hydropic degeneration was investigated. A statistically significant difference existed between the disappearance time of serum hCG after the evacuation of hydatidiform mole as compared with partial mole and hydropic degeneration. The average disappearance time of serum hCG after hydatidiform mole was 99.3 days, after partial mole 58.9 days, and after hydropic degeneration 50.7 days. It is not recommended to start chemotherapy for persistent trophoblastic disease before 100 days after the evacuation of hydatidiform mole, provided there is a steady downward course of the serum hCG level. It is advised to submit cases of supposed hydatidiform and partial moles to a tissue committee for a second opinion.     

Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study

In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group). RESULTS: As compared to placebo, plasma levels of AT III were reduced only in the E2 group (approximately 28%), plasma levels of protein C decreased only in the E2+P group (approximately 4%) and plasma levels of protein S decreased in both the E2 and E2+P group (approximately 21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (approximately 10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (approximately 22%), urokinase plasminogen activator (approximately 25%) and plasminogen activator inhibitor type-1 (approximately 43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (approximately 12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (approximately 31%), but levels of thrombin-antithrombin III complexes, and of plasmin-alpha2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly. CONCLUSION: Short-term E2 and E2+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.     

流感病毒A／越南/1194/2004H5N1毒株灭活裂解疫苗的安全性和免疫原性

背景:在亚洲、非洲和欧洲,致病性H5N1流感病毒引起禽流感在家禽和候鸟中爆发流行,还导致了人类发病和死亡。虽然目前H5N1毒株引起人与人之间的传染不太可能,但它仍可能是未来流感大范围流行的潜在威胁因素。本试验的目的就是评价针对H5N1病毒株的裂解病毒疫苗的安全性和免疫原性。方法:对300名志愿者(年龄为18岁～40岁)进行随机、开放标签的、无对照的Ⅰ期试验。300名志愿者被分为6组:7.5mg血凝素加佐剂组(n=50)、7.5mg血凝素不加佐剂组(n=49)、15mg血凝素加佐剂组(n=50)、15mg血凝素不加佐剂组(n=50)、30mg血凝素加佐剂组(n=51)、30mg血…     

The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study

Background  

To reduce the risk of brain damage children with acute lymphoblastic leukaemia (ALL) are nowadays mainly treated with intrathecal chemotherapy (ITC) instead of central nervous system (CNS) radiation therapy (CRT) to prevent CNS relapse. However, chemotherapy may also lead to cognitive deficits. As growth hormone deficiency (GHD) or impaired growth hormone secretion are frequently found in ALL patients treated with cranial radiation therapy and/or chemotherapy, we hypothesized that GH therapy may reduce cognitive deficits in these patients.     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Parents and children in art

It is an honour to have been asked to contribute to this volume that commemorates the life and work of Spyros Doxiadis. Spyros was, and is still, a vital and stimulating influence on those of us who were fortunate enough to have been his colleague in all phases of his life. My period of closeness to him was when he was working in Sheffield with Ronald Illingworth. At that time (now over 40 years ago) he and Katherine were having their children and my wife and I was having ours. Then words like "bonding" had not become commonplace as today, but the functional patterns of family relationships were something about which we were intensely aware. I particularly remember a summer when we were holidaying on a tidal estuary between Anglesey and Holy Island and recall a moment when Spyros and I were sitting on a grass topped sandbank watching our children and wives at the water's edge "messing around" with a boat. We watched and discussed the beauty of the postures and poses of our womenfolk with the children and the children with each other. It was the memory of that conversation that stimulated me to propose the topic of this essay in Spyros' memory.     

Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased ( p <0.0005) in groups B and C, with a greater increase in group C than in group B ( p < 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.     

Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides

Antibodies (Abs) to MUC1 occur naturally in both healthy subjects and cancer patients and can be induced by MUC1 peptide vaccination. We compared the specificity of natural and induced MUC1 Abs with the objective of defining an effective MUC1 vaccine for active immunotherapy of adenocarcinoma patients. Serum samples, selected out of a screened population of 492 subjects for their high levels of IgG and/or IgM MUC1 Abs, were obtained from 55 control subjects and from 26 breast cancer patients before primary treatment, as well as from 19 breast cancer patients immunized with MUC1 peptides coupled to keyhole limpet hemocyanin (KLH) and mixed with QS-21. The samples were tested with enzyme-linked immunoassays for reactivity with (1) overlapping hepta- and 20-mer peptides spanning the MUC1 tandem repeat sequence; (2) two modified 60-mer peptides with substitutions in the PDTR (PDTA) or in the STAPPA (STAAAA) sequence of each tandem repeat; and (3) four 60-mer glycopeptides with each 1, 2, 3 and 5 mol N-acetylgalactosamine (GalNAc) per repeat. More than one minimal epitopic sequence could be defined, indicating that Abs directed to more than one region of the MUC1 peptide core can coexist in one and the same subject. The most frequent minimal epitopic sequence of natural MUC1 IgG and IgM Abs was RPAPGS, followed by PPAHGVT and PDTRP. MUC1 peptide vaccination induced high titers of IgM and IgG Abs predominantly directed, respectively, to the PDTRPAP and the STAPPAHGV sequences of the tandem repeat. Natural MUC1 Abs from breast cancer patients reacted more strongly with the N-acetylgalactosamine (GalNAc) peptides than with the naked 60-mer peptide, while reactivity with the GalNAc-peptides was significantly reduced (2-tailed p < 0.0001) in the MUC1 IgG and IgM Abs induced by MUC1 peptide vaccination. Whereas in cancer patients glycans appear to participate in epitope conformation, the epitope(s) recognized by MUC1 Abs induced by peptide vaccination are already masked by minimal glycosylation. Therefore, our results indicate that a MUC1 glycopeptide would be a better vaccine than a naked peptide.