Gender differences in the phenotypic expression of Alzheimer's disease in Down's syndrome (trisomy 21)

Twenty-eight individuals with typical Down's syndrome (DS) phenotype (17 males and 11 females; age range: 10-74 years) were investigated for gender differences in the phenotypic expression of Alzheimer-type pathology (ATP). Quantitative neuropathology was performed in the 4 neocortical lobes of the right hemisphere, by counting senile plaques (SP), and neurofibrillary tangles (NFT). ATP was present in 25 middle-aged (> 40 years) individuals (16 males and 9 females). Females had significantly higher (p = 0.03) mean neocortical NFT densities (36.6 per mm2; s.e.m. +/- 6.6) than males (17.9 per mm2; s.e.m. +/- 4.7). None of the females had NFT densities below 10 per mm2, compared with 6 males in whom NFT were either absent or seen in very low densities (< 4 per mm2). Assessment of SP densities in the same cortical regions showed non-significant differences in females (42.4 per mm2; s.e.m. +/- 5.1) compared with males (33.6 per mm2; s.e.m. +/- 2.1). There was clinical evidence of dementia in all the female (8/8) individuals who were prospectively assessed, compared with only 54% (7/13) of males. The male individuals without clinical dementia had absent or low neocortical NFT densities regardless of high SP densities. Female DS cases (mean age: 48.8 years; s.e.m. +/- 1.9) had an earlier onset of dementia than males (mean age: 53.6 years; s.e.m. +/- 1.3; p = 0.05). Female middle-aged DS individuals have an earlier onset, and a more severe form of AD which correlates with higher neocortical NFT rather than SP density.     

HELLP syndrome in the 21st week of pregnancy in mosaic trisomy 9

We report for the first time the case of postabortional HELLP-syndrome in the 21st week of gestation. In this case mosaic trisomy 9 was confirmed by amniocentesis prior to induction. Pertinent history, clinical course and pathoanatomical morphology are described. We emphasize the early onset of the HELLP-syndrome in association with trisomy 9 after abortion. The possibility of interconnections between trisomy 9 and the occurrence of HELLP-syndrome (sparse blood, vessels in the villi, circulatory deficit on the fetal side of the placenta, increased production of e.g. vasopressive substances) is discussed.     

First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21

Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the alpha1 chain of collagen type I, were measured in peripheral blood from women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be stable throughout this period, and though raised FA-2 concentrations were seen at the 10th week of gestation, a statistically significant difference between normal and trisomy 21 affected pregnancies was not found overall. Therefore it seems unlikely that FA-2 has a role in first trimester screening for trisomy 21, despite the fact that significantly higher FA-2 concentrations in trisomy 21 and significantly lower concentrations in trisomy 18 had been previously demonstrated in amniotic fluid in the second trimester.     

Serum markers for Down's syndrome in relation to number of previous births and maternal age

We conducted a study to investigate the effect of parity on the following six serum markers used in screening for Down's syndrome, after adjusting them for ethnic group and maternal weight: alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and dimeric inhibin A. We aimed to estimate the effect of adjusting for any differences found on the screening performance. AFP, uE3, and hCG concentrations were available from 16,666 women with singleton pregnancies without Down's syndrome or neural tube defects and without insulin-dependent diabetes mellitus, who were screened between 15 and 22 weeks' gestational age. Stored serum samples were available on a subset of 1347 women and these were used to measure free alpha-hCG, free beta-hCG, and inhibin A. Serum concentrations were expressed as multiples of the median (MOM) for women of the same gestational age, weight, and ethnic group. Of the six markers, only hCG levels were affected by parity; hCG levels decreased by 3.1 per cent per previous birth (95 per cent confidence interval 2.2-4.0 per cent); there was no significant relationship between the number of previous abortions and hCG level after adjustment for the number of previous births. The effect of previous births on hCG was not due to maternal age. Only AFP was affected by maternal age, but the effect was small; levels increased by 4.4 per cent per 10 years of age (3.2-5.7 per cent). It is not worthwhile adjusting serum markers for parity or for maternal age in prenatal screening for Down's syndrome because their effect on the performance of screening is negligible.     

Amniotic fluid alpha-fetoprotein levels during midtrimester of trisomy pregnancies

To investigate the association between low amniotic fluid alpha-fetoprotein (AFP) and trisomy pregnancies, we retrospectively reviewed 26 trisomy pregnancies including 18 fetuses with Down's syndrome and eight with trisomy 18. The amniotic fluid AFP median values of Down's syndrome, trisomy 18, and the study groups were 0.73 MoM, 1.15 MoM, and 0.85 MoM, respectively. There was a significant difference between the mean values of the Down's syndrome-affected fetuses (0.78 +/- 0.29 MoM) and that of the control group (p < 0.001), whereas no such difference was found for that of trisomy 18-affected fetuses (1.16 +/- 0.38 MoM). Only three patients in the study group (3/26, 11.5%) had an amniotic fluid AFP value below 0.5 MoM, including the two cases of Down's syndrome (2/18, 11.1%) and one case of trisomy 18 (1/8, 12.5%). Most of the values for the trisomy pregnancies were within the normal range, thereby precluding the possibility of using this measurement as an alternative to fetal karyotyping as a screening test for Down's syndrome or other trisomy pregnancies.     

Cigarette smoking and trisomy 21 at amniocentesis

Several studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women (n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21-control matched m-tuples in which diagnosis was by amniocentesis at 14-26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4-1.6] and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9-2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4-1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of Down's syndrome and testicular cancer

PURPOSE: We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. MATERIALS AND METHODS: Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. RESULTS: The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. CONCLUSIONS: Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.     

Biochemical markers of cerebral damage

We report a case of Aspergillus flavus endocarditis in a 6-year-old boy with stage IV neuroblastoma with no pre-existing cardiac disease. The infection was successfully treated with high-dose liposomal amphotericin (AmBisome) once daily. Recurrence was prevented with itraconazole oral solution once daily as maintenance therapy. Adjunctive surgery was not required. The patient's cardiac function was uncompromised, but subsequent death from progressive neuroblastoma prevented long-term follow-up.     

Biochemical markers of strophanthin arrhythmia

The increase of the concentration of fatty acids, the reduction in the concentration of serotonin, the lowering of the activity of glucose-6-phosphate dehydrogenase and transketolase, and the development of compensated metabolic acidosis were discovered in the stage that preceded strophanthine arrhythmia. These characteristics may be recommended for a wider use on the clinical basis for predicting arrhythmias in the treatment of cardiac glycosides.     

Biochemical markers of bone turnover

INTRODUCTION: Giant cell fibroblastoma is a rare mesenchyma tumor of childhood having many similarities with dermatofibrosarcoma protuberans in adults. OBSERVATION: We report the case of a 28-year-old woman presenting a subcutaneous inter-mammary mass associating both tumors. Immunohistochemistry showed an expression of CD 34 only by dermatofibrosarcoma protuberans cells. DISCUSSION: It is important to stress: the rarity of this association, the difficulty to confirm the diagnosis and to establish the links between these two tumors: simple association (as in our case), transformation or recurrence of giant cell fibroblastoma in dermatofibrosarcoma protuberans.     

Decreased dendritic branching in frontal, motor and limbic cortex in Rett syndrome compared with trisomy 21

Although some of the susceptibility to Graves' disease is conferred by genes in the human leucocyte antigen (HLA) region on the short arm of chromosome 6, other genetic factors must also predispose. Among the cytokines involved in thyroid autoimmunity interferon-gamma (IFN-gamma) plays a key role in the pathogenesis of Graves' disease. We therefore analyzed the first intron of the IFN-gamma gene for a dinucleotide (CA) repeat polymorphism on chromosome 12q. Two hundred two Caucasian patients with Graves' disease and 214 Caucasian controls were analyzed by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis technique: eight different alleles designated as IFN-gamma*1 to IFN-gamma*8 could be differentiated. Among Graves' disease patients IFN-gamma*5 (12.9% vs. 6.8%, p < 0.04) was significantly more frequent whereas IFN-gamma*2 (2.5% vs. 9.8%, p < 0.002) was significantly less frequent. Patients positive for the genetic susceptibility marker HLA DQA1*0501 had significantly more IFN-gamma*3 alleles (13.6% vs. 2.6%, p < 0.009) and IFN-gamma*5 alleles (22.1% vs. 7.6%, p < 0.03) compared with DQA1*0501 positive controls. Also, among patients with endocrine ophthalmopathy IFN-gamma*3 (17.9% vs. 4.2%, p < 8 x 10(-6)) and IFN-gamma*5 (18.9% vs. 7.0%, p < 0.003) were significantly more frequent compared with controls. Although a significant association of IFN-gamma microsatellite polymorphism was observed, only a small proportion of Graves' disease patients have these markers. Thus, it is likely that the detected microsatellite polymorphisms play only a minor role in the susceptibility to Graves' disease.     

Down's syndrome, ageing and fragile sites

Fragile sites have been interesting for mapping chromosomal regions involved in disease and ageing. The chromosomal fragile site expression from 38 Down's syndrome (DS) individuals aged 0-48 years was investigated in blood peripheral lymphocytes. Fragile sites were statistically characterized as the minimum expected number of lesions per band based on a Poisson distribution. The results showed that the fragile site 2q11 was associated with the DS condition and fragile sites 5q31, 6p21 and 9q12 with ageing in DS subjects. Fragility in 6p21 has also been associated with Alzheimer's disease patients.     

Biochemical markers for bone activity and osteoporosis

Osteoporosis is characterized by reduced bone mass, derangement of bone microscopic architecture and increased risk of fractures. For the evaluation of this risk an important role is played by bone mass peak (measurable with mineralometric techniques) and the rate of bone resorption. The latter can be assessed by means of many laboratory indexes, taken as markers of bone cells activity. The latest markers of osteoblastic activity are osteocalcin and the terminal fragment of type I pro-collagen. On the other hand pyridinolines are considered markers of bone resorption. The authors describe the assay procedures and the clinical meaning of these markers of bone metabolism.     

Free radicals in the origin and clinical manifestation of Down's syndrome

The high level of free radicals and antioxidant protection disbalancing cause the chromosome nondisjunction in meiosis, appearance of trisomy 21 and fetuses with Down's syndrome, age-dependent pathology, of parent's mosaic clone, clinical manifestations of the syndrome, diseases in relatives, recurrent cases of trisomy 21. The comparative analysis of clinical traits of Down's syndrome and pathological changes in families with after-effects of radiation exposure was carried out. The factors causing an increase in the level of free radicals were considered.     

Endometrial and fetoplacental markers in pregnancies with fetal congenital nephrosis

BACKGROUND: Interview studies which employ qualitative methodology are often concerned with classifying behaviours or attitudes and an ideal sample of research subjects displays variety in the attitudes or behaviours under scrutiny. OBJECTIVE: This paper describes the development of a questionnaire which measures GPs' attitudes towards discussing smoking with patients with the intention of using this instrument to select GPs with diverse views for a qualitative interview study. METHOD: Thirteen attitude statements with an accompanying Likert-type scale were completed by 327 GPs in one FHSA area. Factor analysis of responses produced two subscales: 'perceived efficacy' and 'enthusiasm'. Reliability and validity of these were examined. RESULTS: Each subscale had good internal reliability and preliminary exploration of construct validity supported the notion that the subscales were valid. CONCLUSION: The use of this type of instrument in sampling GPs for qualitative studies could be effective for selecting subjects with a diversity of views towards the research topic.     

Collagen type VI gene expression in the skin of trisomy 21 fetuses

Using site-directed mutagenesis, changes of Tyr221 in plasminogen activator inhibitor-1 (PAI-1) have provided mutants with normal activity, but with increased stability. At physiological conditions, the transition of the PAI-1 mutants Tyr221His and Tyr221Ser to the latent form was significantly prolonged (half-lives 14.8 and 4.1 h, respectively) as compared to wild-type PAI-1 (2.0 h). Their half-lives, especially for the Tyr221Ser mutant, were even more prolonged in the presence of vitronectin (23.8 and 53.7 h, respectively). While wild-type PAI-1 was more stable at lower pH, the PAI-1 mutants Tyr221His and Tyr221Ser had stability optima at about pH 6.5, but displayed shorter half-lives at pH 5.5.