Time related bias in longitudinal studies using dual photon absorptiometry.

Examining the bone mineral density (BMD's) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July-December 1989, January-June 1990 or July-December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p < 0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p < 0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

Placental inflammation and perinatal transmission of HIV-1

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.     

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.     

Coexistence of an adrenocortical carcinoma with an abdominal ganglioneuroma in a child

We report a 3-year, 5-month-old boy with an adrenocortical carcinoma. These tumours are rare and highly malignant in childhood. In most cases they are functional, secreting adrenocortical hormones. In this case there was a misleading coexistence with a second abdominal neoplasm, which was a ganglioneuroma; this is a rare benign tumour arising from the sympathetic nervous system. The imaging investigations and their findings are discussed and correlated with pathology. Received: 15 January 1997 Accepted: 15 October 1997     

Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas.

PURPOSE: The reliability of immunohistochemistry for subdividing diffuse large B-cell lymphomas (DLBCL) into germinal center B-cell-like (GCB) and non-GCB prognostic subgroups is debated. In this study we evaluated the prognostic significance of such subgrouping on a series of 153 DLBCL patients. Furthermore, we investigated whether both subgroups could comprise clinicopathologic entities recognized by their morphology and characterized by a distinct phenotype, specific genetic abnormalities, and clinical characteristics. PATIENTS AND METHODS: All samples from patients were reviewed and morphologically subdivided into large cleaved, immunoblastic, and not otherwise specified DLBCL. GCB and non-GCB immunohistochemical profiles were established. The presence of chromosomal translocations involving BCL2, BCL6, and MYC and/or rearrangements of these genes was investigated. RESULTS: Subdividing DLBCL with either a GCB or non-GCB immunophenotypic profile was not of prognostic significance. Nevertheless, CD10 expression was a predictor of favorable outcome, whereas high bcl-2 expression and BCL6 rearrangement were adverse predictors of disease-free survival. Interestingly, large cleaved DLBCL was clearly associated with a GCB immunophenotypic profile, CD10 expression, BCL2 rearrangement, age younger than 60 years, and low to low/intermediate International Prognostic Index risk, but was not of prognostic significance. In contrast, immunoblastic morphology was associated with a non-GCB profile and was a significant predictor of unfavorable DFS. CONCLUSION: Subdividing DLBCL into subgroups based on their immunohistochemical profile was not of prognostic significance. Nevertheless, it allowed the additional characterization of two lymphoma subgroups previously recognized in the Working Formulation. Both correspond to two distinct clinicopathologic entities within the DLBCL.     

How to use a nasopharyngeal prong in Pierre Robin sequence

Pierre Robin sequence (PRS) describes a small mandible with retrognathia, an elevated and posteriorly positioned tongue, and an associated U-shaped cleft palate. The retracted tongue may obstruct the airway leading to respiratory failure, with failure to thrive and adverse neurodevelopmental outcomes if not addressed. If the airway obstruction cannot be overcome with conservative measures, there are non-surgical and surgical options. A nasopharyngeal prong (NPP) is a non-surgical, temporary treatment that avoids the complications inherent in an operation, especially given the natural history of mandibular growth and improved airway obstruction in PRS. Although the use of a prong requires training, support, and follow up, it effectively bypasses the obstruction in the majority of children with PRS, and allows the child to outgrow the airway obstruction until the prong is no longer required. On average, the prong can be removed between 6 and 12 months of age.