CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.     

Analysis of longitudinal data from twins

Longitudinal data from twin pairs may be used to determine how the genetic effects influencing a quantitative trait change with age. Here a model for mixed longitudinal data of Huggins and Loesch [1998] on unrelated individuals is extended to twin studies. The model is fitted using robust statistical methods and a bootstrap procedure is proposed to estimate the percentiles. The method is applied to longitudinal twin data on body mass index in male and female twin pairs aged 5-18 years.     

Ultrastructural evidence for alterations of pituicytes in reanimated rats in connection with experimentally induced clinical death

This work was undertaken to elucidate some ischaemic and postischaemic changes appearing in the neurohypophysial pituicytes of rats which underwent the incident of clinical death. The incident was experimentally induced by compression of the vascular bundle of the heart for 2.5 min. The ultrastructural organization of pituicytes was investigated directly after reanimation and 3 days after surviving the clinical death. These studies provided evidence for numerous alterations in pituicytes indicating a high sensitivity of the cells to the ischaemic conditions. Thus, four varieties of pituicytes were revealed based on their ultrastructural characteristic, namely: "swollen", "dark", "vacuolated" and "intermediate". Except for the "intermediate" pituicytes (abounding in liposomes), embedding of neurosecretory axons in pituicytes was commonly observed, and thus, several phases of axon degeneration due to pituicytes were noted, including disintegrated axolemma and appearance of a peculiar arrangement of microtubules. These findings strongly support the hypothesis of neuronal-glial interaction in the neurohypophysis under physiological and/or pathophysiological conditions. Thus, the results of the present study are discussed in terms of pituicytes involvement in the mechanisms of control (restriction) of neurohypophysial hormones release in reanimated rats.     

Changes of jugular venous blood temperature associated with measurements of cerebral blood flow using the transcerebral double-indicator dilution technique

BACKGROUND AND OBJECTIVE: The transcerebral double-indicator dilution technique is a recently developed method to measure global cerebral blood flow at bedside. It is based on bolus injection of ice-cold indocyanine green dye and simultaneous recording of resulting thermo- and dye-dilution curves in the aorta and the jugular bulb. However, with this method 40 mL of ice-cold solution is administered as a bolus. Therefore, this prospective clinical study was performed to elucidate the effects of repeated administration of indicator on absolute blood temperature and on cerebral blood flow and metabolism. METHODS: The investigation was performed in nine male patients scheduled for elective coronary artery bypass grafting. Absolute blood temperature was measured in the jugular bulb and in the aorta before and after repeated measurements using the transcerebral double-indicator dilution technique. RESULTS: During the investigated time course, the blood temperature in the jugular bulb, compared to the aorta, was significantly higher with a mean difference of 0.21 degrees C. The administration of an ice-cold bolus reduced the mean blood temperature by 0.06 degrees C in the jugular bulb as well as in the aorta. After the transcerebral double-indicator dilution measurements a temperature recovery to baseline conditions was not observed during the investigated time period. Cerebral blood flow and cerebral metabolism did not change during the investigated time period. CONCLUSIONS: Repeated measurements with the transcerebral double-indicator dilution technique do not affect absolute jugular bulb blood temperatures negatively. Global cerebral blood flow and metabolism measurements remain unaltered. However, accuracy and resolution of this technique is not high enough to detect the effect of minor changes of physiological variables.     

Application of robust pedigree analysis in studies of complex genotype-phenotype relationships in fragile X syndrome.

Relationships between the fragile X dynamic mutation and palmar and finger epidermal ridge measures were assessed using a robust modification of the maximum likelihood estimators for pedigree data. A total of 34 extended families affected with fragile X syndrome were used. Phenotypic traits included ridge count on the thumb and ridge breadth measured in the second palmar interdigital area bilaterally. Genotypic measures were represented by the number of CGG repeats in the FMR1 gene, the levels of specific FMR1 protein (FMRP), fragile X category defined by the size of the CCG repeat, and methylation status of the gene. The results demonstrated a significant fragile X effect (related to the number of CGG repeats) in the thumb ridge count in males. This effect was more evident in ridge breadth and was found in both sexes. However, the relationship between both phenotypic traits and the level of FMRP was nonsignificant. The study makes a useful contribution to the development of methodologies for the analysis of genotype-phenotype relationships in dynamic mutations, especially in overcoming extensive variability in both the genotype and phenotype, and in approaching the statistical problems related to intergenerational changes in repeat size. The findings support the hypothesis that the fragile X mutation affects limb development during an early fetal period.     

Vaginal trichomoniasis among HIV patients attending primary health care centers of Jos,Nigeria

ObjectiveTo determine the prevalence of trichomonal infection in HIV/AIDS and non-HIV control group of patients in a population of women with abnormal vaginal discharge.MethodsWe conducted a simple cross-sectional study. Primary health care centers in Jos metropolis and Jos University Teaching Hospital, during December 2006 to December 2007. Seven hundred high vaginal swabs were collected; 350 from HIV positive and another 350 from HIV-negative control group of patients with abnormal vaginal discharge attending primary health care centers in Jos metropolis and analysed for microscopy and culture in Jos University Teaching Hospital. Data on epidemiologic indices from the patients, using structured interviewer-administered questionnaires were collected.ResultsThe rate of trichomoniasis among all participants in the study was 17% (n=120/700). The prevalence rate of trichomoniasis among persons with HIV was 24% while it was found to be 10.3% among HIV negative controls. The difference was statistically significant (χ² =23.172; df=1; P<0.05). The rate of co-infection of Trichomonas vaginalis (T. vaginalis) in bacterial vaginosis was 42% (n=50/120), while it was 24% (n=29/120) in candidiasis. The singles had a 35% high rate of trichomonal infection. The infected women had a median age of 26 years, and a median number of 3 intra-vaginal sex partners per week.ConclusionsThere was a significant statistical difference in prevalence of T. vaginalis between HIV/AIDS group and non-HIV(control) group of patients in the study (P<0.05). Local HIV prevention strategies should target such women with trichomonal infection for intervention efforts, especially in HIV endemic area of sub-continent of Africa to further reduce the burden of HIV in the population.     

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy

We performed a phase I trial of recombinant human interleukin-11 (rhIL- 11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.     

Impairment in the cognitive functioning of men with fragile X-associated tremor/ataxia syndrome (FXTAS)

Disorders associated with fragile X syndrome involve a trinucleotide (CGG) repeat expansion in the FMR1 gene. Recently, a progressive movement disorder (fragile X-associated tremor/ataxia syndrome [FXTAS]) has been identified in premutation carriers, persons with 55 to 200 CGG repeats. In addition to ataxia, action tremor, and Parkinsonism, early case reports suggested that FXTAS involves impaired cognition, but the precise nature of the impairment has not been elucidated. In this first, preliminary study of the subject, circumscribed aspects of cognitive functioning were examined in 25 men with FXTAS. Subjects' performance on the cognitive tests was compared with normative data. Scores on two measures of executive cognitive functioning showed a high prevalence of substantial impairment. Capacity for inhibition was severely affected in one-quarter of this highly educated sample; information processing speed was profoundly impaired in most subjects. Although mean verbal and performance IQ scores were not significantly different from the general population, they were quite low given the sample's educational level. Cognitive and functional impairment was greater for men with more CGG repeats, although number of repeats was not associated with age of onset of either tremor or ataxia. The results provide evidence that FXTAS involves marked impairment of executive cognitive abilities.     

Surgical trauma and vein graft failure: further evidence for a role of ET-1 in graft occlusion

The saphenous vein (SV) is the most commonly used conduit for coronary artery bypass surgery. However, using traditional techniques, the occlusion rate for the SV is high, with over 50% of grafts failing within 10 years. In conventional coronary artery bypass surgery the SV is exposed to considerable damage during preparation for grafting. Recently, an increased graft patency has been described using a 'no-touch' technique, whereby the vein is prepared with minimal vascular trauma. There is evidence that the success of this form of coronary artery bypass surgery is a result, at least in part, of the retention of tissue-derived nitric oxide. We have examined the effects of conventional SV harvesting on vessel morphology, cell proliferation, endothelin-1 and its receptors. Considerable damage was observed in veins prepared using conventional surgery compared to 'no-touch' veins. The vessel wall exhibited evidence of surgical trauma, with regions of denudation of the luminal endothelium caused by distension. Endothelin-1 and endothelin-A receptors were present at subintimal regions of conventional SV segments where proliferating cells were identified. Endothelial endothelin-B receptors were also revealed that were absent at areas of distension-induced damage to the endothelium. These results suggest that endothelin-1 plays a role in vein graft failure, predominantly via the endothelin-A receptor.     

Effect of the fragile X status categories and the fragile X mental retardation protein levels on executive functioning in males and females with fragile X

The effects of a fragile X disorder on executive function impairment were assessed in 144 extended families, which included individuals with fragile X premutation and full mutation and their relatives without fragile X. A modification of the maximum-likelihood estimators for pedigree data, as well as ordinal logistic regression, were used in data analysis. The most outstanding deficit, occurring especially in males, involved impaired capacity to use an intention to regulate purposeful behavior. This deficit occurred independently of general cognitive impairment but was related to depletion of fragile X mental retardation 1 gene protein product. The other executive function deficits were accounted for by the general cognitive impairment. Possible mechanisms of the effect of fragile X premutation on impairments of executive functioning are considered.