An immunohistochemical study of human fetal liver in the Meckel-Gruber syndrome

AIMS: The ductal plate abnormality of the liver in fetuses with the Meckel-Gruber syndrome has been well characterised, but its aetiology remains unknown. We have analysed liver structure in six fetuses with this syndrome, using routine histology, immunocytochemistry, and electron microscopy. METHODS: Liver tissue from six fetuses of 11-27 weeks gestational age was examined by immunoperoxidase staining with antigens to cyokeratin (AE1/3) and polyclonal CEA. We also examined the ultrastructure of the syndromic fetal liver. The findings were compared with livers of control fetuses obtained from miscarriages, of similar size and gestational age but without dysmorphic features or developmental anomalies. RESULTS: The ductal plate abnormality was present in all the fetuses with the Meckel-Gruber syndrome. There were abnormalities of biliary excretion in all syndromic fetuses. Ultrastructural studies of the portal tract revealed abnormal collagen bundles in the Meckel-Gruber syndrome. CONCLUSIONS: Our findings, in conjunction with other reports in the literature, suggest that the ductal plate abnormality may be caused by failure of anastomosis of the intra- and extrahepatic biliary systems, perhaps in association with abnormalities of the portal tract stroma and biliary excretion.     

Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study

OBJECTIVE: To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery. STUDY DESIGN: Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2). RESULTS: Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%). CONCLUSION: Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.     

Ecological validity of walking speed assessment after traumatic brain injury: a pilot study

OBJECTIVE: To assess the ecological validity of walking speed measurement after traumatic brain injury (TBI). PARTICIPANTS: Ten people with TBI who could walk independently and were participating in a rehabilitation program. DESIGN: Walking speed on 3 clinical gait tests (comfortable and fast pace over a 10-m distance and a 6-minute walk test) in 3 "natural" environments (a corridor in a brain injury rehabilitation unit, a car park of a metropolitan shopping center, and inside a metropolitan shopping center). Normative data were collected for 275 able-bodied pedestrians as they walked in the 3 natural environments. RESULTS: For subjects with TBI, agreement between the speeds used in the clinical gait tests and the natural environments was poor (intraclass correlation coefficient [ICC] values ranged from -0.24 to 0.63). The closest speed match was the comfortable paced 10-m walk test and walking in a corridor of a brain injury rehabilitation unit (ICC 0.63). Able-bodied pedestrians walked at significantly faster speeds than did subjects with TBI in all 3 natural environments. CONCLUSIONS: Comfortable walking speed appears to have the highest ecological validity of the clinical gait tests investigated. Practice in natural and more complex environments should be incorporated into walking rehabilitation programs for people with TBI.     

A novel in vivo procedure for volumetric flow measurements

We report on a novel procedure for invasive volumetric blood flow measurements using a commercially available Doppler flow wire system, which could, until now, only measure flow velocity. We here describe a method applicable in vivo to generate both velocity and cross-sectional area information from the same pulsed-wave Doppler signal for volumetric flow assessment. We demonstrate its feasibility and validation in vivo in pig coronary arteries. Our Doppler-derived volumetric flow measurements were compared with the respective transit-time flow and showed an excellent correlation (r = 0.969; p < 0.0001). Agreement between transit-time and Doppler-derived flow measurements could be observed for flow conditions ranging from 30 to 180 mL/min. The mean values for the two methods were 71.4 +/- 43.7 mL/min and 71.3 +/- 42.2 mL/min, respectively. We conclude that this technique might possibly be introduced into future clinical practice as an invasive procedure of choice for the assessment of volumetric blood flow.     

Toxic proteins released from mitochondria in cell death

A plethora of apoptotic stimuli converge on the mitochondria and affect their membrane integrity. As a consequence, multiple death-promoting factors residing in the mitochondrial intermembrane space are liberated in the cytosol. Pro- and antiapoptotic Bcl-2 family proteins control the release of these mitochondrial proteins by inducing or preventing permeabilization of the outer mitochondrial membrane. Once released into the cytosol, these mitochondrial proteins activate both caspase-dependent and -independent cell death pathways. Cytochrome c was the first protein shown to be released from the mitochondria into the cytosol, where it induces apoptosome formation. Other released mitochondrial proteins include apoptosis-inducing factor (AIF) and endonuclease G, both of which contribute to apoptotic nuclear DNA damage in a caspase-independent way. Other examples are Smac/DIABLO (second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI) and the serine protease HtrA2/OMI (high-temperature requirement protein A2), which both promote caspase activation and instigate caspase-independent cytotoxicity. The precise mode of action and importance of cytochrome c in apoptosis in mammalian cells has become clear through biochemical, structural and genetic studies. More recently identified factors, for example HtrA2/OMI and Smac/DIABLO, are still being studied intensively in order to delineate their functions in apoptosis. A better understanding of these functions may help to develop new strategies to treat cancer.     

Depression in France and Brazil: factorial structure of the 17-item Hamilton Depression Scale in inpatients

Among various research strategies for depression, the cross-cultural approach is a useful tool to investigate depressive disorders. The Hamilton Rating Scale for Depression was applied to 130 depressed inpatients in France and Brazil. Items were factorized by principal component analysis with Varimax rotation using the Kaiser or simulation method for factor sorting. Three factors were obtained in France, and four in Brazil. The first factor includes the core symptoms of depression in both samples. Qualitative and quantitative differences appeared in the anxiety factor between Brazilian and French samples. Insomnia items appeared as another factor for both groups. A limitation of this study is that it was conducted with small inpatient samples. Principal component analysis of the Hamilton Rating Scale for Depression for depressive inpatients in these two countries showed a similar structure. Differences observed were in the way anxiety items were distributed.     

Alveolar rhabdomyosarcoma of the cervix

BACKGROUND: Alveolar rhabdomyosarcoma (RMS) has a high risk for local and distal failure. Multimodal management of a patient with alveolar RMS of the cervix uteri is outlined. CASE: A 39-year-old woman suffered from alveolar RMS of the cervix without involvement of uterus and parametrium. She was treated with total hysterectomy and left salpingo-oophorectomy. Systemic chemotherapy and pelvic irradiation were also offered. She remains in clinical remission 3 years after presentation. CONCLUSION: Postoperative chemotherapy and irradiation could be effective treatments for alveolar rhabdomyosarcoma of the cervix in adult patients.