Gravidity-dependent associations between interferon response and birth weight in placental malaria.

BACKGROUND: Maternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal-fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes. METHODS: 40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-ß, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded. RESULTS: Histological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-ß and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-ß levels and higher birth weights (ß = 101.2 g per log2-fold increase in IFN-ß expression, p = 0.042). This association was strongest in primigravidas with placental malaria (ß = 339.0, p = 0.006). CONCLUSIONS: These results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-ß levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria.

Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion.

Cellular senescence suppresses cancer by stably arresting the proliferation of damaged cells. Paradoxically, senescent cells also secrete factors that alter tissue microenvironments. The pathways regulating this secretion are unknown. We show that damaged human cells develop persistent chromatin lesions bearing hallmarks of DNA double-strand breaks (DSBs), which initiate increased secretion of inflammatory cytokines such as interleukin-6 (IL-6). Cytokine secretion occurred only after establishment of persistent DNA damage signalling, usually associated with senescence, not after transient DNA damage responses (DDRs). Initiation and maintenance of this cytokine response required the DDR proteins ATM, NBS1 and CHK2, but not the cell-cycle arrest enforcers p53 and pRb. ATM was also essential for IL-6 secretion during oncogene-induced senescence and by damaged cells that bypass senescence. Furthermore, DDR activity and IL-6 were elevated in human cancers, and ATM-depletion suppressed the ability of senescent cells to stimulate IL-6-dependent cancer cell invasiveness. Thus, in addition to orchestrating cell-cycle checkpoints and DNA repair, a new and important role of the DDR is to allow damaged cells to communicate their compromised state to the surrounding tissue.

Hepatic toxocariasis: US, CT and MRI findings.

Visceral larva migrans (VLM) most commonly occurs as a febrile disease of childhood particularly affecting children between 1 and 7 years of age. Pulmonary, dermatological, hepatic, lymphatic, cardiac, rheumatological and neurological manifestations may occur. VLM seems to be a rare disease in adults. We report the imaging findings of a woman with hepatic toxocariasis. Ultrasonography showed a solitary hepatic lesion measuring 4 x 3 cm, displaying a hypoechoic-heterogeneous pattern with ill-defined borders and distal acoustic enhancement, located in the right sub-diaphragmatic area. Two enlarged periportal lymph nodes and moderately dilated intrahepatic biliary ducts were also noted. The probability of toxocariasis was discussed, based on sonographic and biopsy findings, and the final diagnosis was confirmed by a specific ELISA test. In summary, a clinical picture of cholestasis initially resembling hepatitis or malignancy should be further evaluated by imaging techniques, and the ultrasound examiner should be familiar with the possible findings of hepatic toxocariasis, which consist of focal ill-defined hepatic lesions, hepato-splenomegaly, biliary dilatation, sludge and periportal lymph node enlargement.

Human fascioliasis.

Fasciola hepatica, a zoonotic liver fluke, can also cause disease in humans. Common symptoms are epigastric pain, upper abdominal pain and malaise. Fever and arthralgia are common in acute fascioliasis. Eosinophilia is the predominant laboratory finding, especially in patients with the acute form of the disease. Diagnosis and treatment is not easy, as physicians rarely encounter this disease, and effective drugs are not available in many countries. Human fascioliasis may be underestimated. Patients with eosinophilia and abdominal pain should be evaluated for F. hepatica infestation by parasitological, radiological and serological tests.

Conformational changes of the 120-kDa Na+/Ca2+ exchanger protein upon ligand binding: a Fourier transform infrared spectroscopy study.

The 120-kDa Na+/Ca2+ exchanger was purified and reconstituted into lipid vesicles. The secondary structure composition of the exchanger was 39% alpha-helices, 20% beta-sheets, 25% beta-turns, and 16% random coils, as analyzed by Fourier transform infrared attenuated total reflection spectroscopy. The secondary structure composition of the COOH-terminal portion of the protein was compatible with a topology model containing 4-6 transmembrane segments. Furthermore, the secondary structure of the NH2-terminal portion of the cytoplasmic loop was analyzed and found to be different from that of the COOH-terminal portion. Ca2+ and/or the exchange inhibitory peptide (XIP) failed to affect the secondary structure of the 120-kDa protein. Tertiary structure modifications induced by Ca2+ and XIP were analyzed by monitoring the hydrogen/deuterium exchange rate for the reconstituted exchanger. In the absence of ligand, 51% of the protein was accessible to solvent. Ca2+ decreased accessibility to 40%, implicating the shielding of at least 103 amino acids. When both Ca2+ and XIP were added, accessibility increased to 66%. No modification was obtained when XIP was added alone. Likewise, in the presence of Ca2+, XIP failed to modify the tertiary structure of the 70-kDa protein, suggesting that XIP acts at the level of the COOH-terminal portion of the intracellular loop. The present data describe, for the first time, conformational changes of the Na+/Ca2+ exchanger induced by Ca2+ and XIP, compatible with an interaction model where regulatory Ca2+ and inhibitory XIP bind to distinct sites, and where XIP binding requires the presence of Ca2+.

Motor performance after posteroventral pallidotomy and VIM-thalamotomy in Parkinson's disease: a 1-year follow-up study.

Twenty-three patients with Parkinson's disease underwent stereotactic surgery. To study the long-term motor performance, the patients were evaluated at the pre-operative period and at the 1st, 3rd, 6th, and 12th post-operative months, with the following scales: Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Larsen's Scale for Dyskinesias. The patients under levodopa therapy were assessed both in "on" and "off" periods. Fourteen unilateral ventrolateral thalamotomies (VLT), 4 unilateral posteroventral pallidotomies (PVP), 2 bilateral PVP, and 3 VLT with contralateral PVP were performed. The motor improvement was significant and long-lasting in the "off" period, except for 2 patients. The "on" period quality improved, mainly due to the control of dyskinesias. The improvement of dyskinesias was long-lasting for the majority of the patients. There was no significant decrease in the levodopa dose. Three patients showed permanent complications, but none was severe.

Fourier transform infrared spectroscopy study of the secondary and tertiary structure of the reconstituted Na+/Ca2+ exchanger 70-kDa polypeptide.

The secondary structure of the purified 70-kDa protein Na+/Ca2+ exchanger, functionally reconstituted into asolectin lipid vesicles, was examined by Fourier transform infrared attenuated total reflection spectroscopy. Fourier transform infrared attenuated total reflection spectroscopy provided evidence that the protein is composed of 44% alpha-helices, 25% beta-sheets, 16% beta-turns, and 15% random structures, notably the proportion of alpha-helices is greater than that corresponding to the transmembrane domains predicted by exchanger hydropathy profile. Polarized infrared spectroscopy showed that the orientation of helices is almost perpendicular to the membrane. Tertiary structure modifications, induced by addition of Ca2+, were evaluated by deuterium/hydrogen exchange kinetic measurements for the reconstituted exchanger. This approach was previously proven as a useful tool for detection of tertiary structure modifications induced by an interaction between a protein and its specific ligand. Deuterium/hydrogen exchange kinetic measurements indicated that, in the absence of Ca2+, a large fraction of the protein (40%) is inaccessible to solvent. Addition of Ca2+ increased to 55% the inaccessibility to solvent, representing a major conformational change characterized by the shielding of at least 93 amino acids.

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger.

The Na/Ca exchanger is associated with 160, 120 and 70 kDa polypeptides whose nature is poorly understood. We have purified and characterized the Na/Ca exchanger from bovine cardiac sarcolemmal vesicles (SLVs) by using ion-exchange and affinity chromatographies. The Na/Ca exchanger-enriched fraction was reconstituted into asolectin liposomes [lipid to protein ratio 10:1 (w/w)] that showed Na/Ca exchange activity. Under non-reducing conditions, SDS/PAGE showed a single 70 kDa polypeptide, which was further characterized by immunoblots with different antibodies: SWant, raised against the purified exchanger protein; NH2-terminus, residues 1-21; NCX1, residues 393-406; and Exon F, residues 622-644. Immunoblots under reducing conditions with SWant, NH2-terminus and NCX1 showed three bands migrating at 160, 120 and 70 kDa for SLV preparations, whereas Exon F reacted only with the 160 and 120 kDa bands. Under non-reducing conditions, immunoblots with purified reconstituted Na/Ca exchanger showed a single band at 70 kDa reacting with SWant, NH2-terminus and NCX1 but not with Exon F. We conclude that the 70 kDa protein is associated with Na/Ca exchange activity, has the same N-terminal sequence as the cloned bovine cardiac exchanger, and has its length decreased by at least 35% from its C-terminal portion as compared with that of the wild-type exchanger.

[Complications and outcome of implantable infusion pumps: apropos of 60 cases]. / Complications et devenir des chambres implantables: à propos de 60 cas.

The aim of this study was to analyse the complications and the outcome in 59 patients with 60 implantable ports for cancer chemotherapy. Perioperative complications included: subcutaneous haematoma (n = 6), wrong position of the catheter tip (n = 2), accidental intravascular injection of lidocaine with adrenaline (n = 1), vagal reflex (n = 1) and pneumothorax (n = 1). Late complications included extravasation of drugs (n = 4), wound dehiscence (n = 1), spontaneous migration of the catheter tip (n = 2), venous thrombosis (n: = 2), septicaemia (n = 6), local discomfort (n = 6) and ports' obstruction (n = 15). In 11 cases, repermeabilization was possible with heparin or streptokinase. Patients were followed up to 40 months, 37% died with a patent port, 6% died with an obstructed port and 45% are still alive with a functional port. Twelve percent of the ports were removed. The lack of life-threatening complications, the high rate of satisfied patients (85%) and the long mean period of use (11 months) in this study are similar to those published in the literature and confirm the value of implantable ports for chemotherapy.

[Wilms' tumors, 12 case reports]. / Tumeurs de Wilms,à propos de douze cas.

The treatment of Wilms' tumor has shown a great success in the pediatric oncology. Our study, which includes 12 cases of nephroblastoma, between 1979 and 1987, has confirmed this results. This tumor that shows no sex prevalence, occurs in a mean age of 2.5 years. The volume of the mass is the most presenting sign in 75% of the cases, I.V.P. confirm the diagnosis in 90% of the cases. Remission occurred in 5 infants who have been in stage I, the other cases who are in stage II to V have bad prognosis. In the future, we hope more advancement in the cure of Wilms tumor, and all the remaining questions will find their answer.

A study of the biochemical characteristics of NADP+ isocitrate dehydrogenase from the liver and kidney of the Arabian camel (Camelus dromedarius).

1. NADP+ isocitrate dehydrogenase was partially purified from camel liver and kidney by an FPLC. 2. The specific activity of the purified preparation from liver was 63.5 mumol/min/mg protein and from the kidney was similar, 58.7 mumol/min/mg protein. 3. The enzyme from the two sources were similar in their pH optimum (7.6), electrophoretic mobility and stability to thermal inactivation at 60 degrees C. 4. Heat inactivation was accelerated by oxidized glutathione and cystine and decreased by dithiothreitol, reduced glutathione and cysteine. 5. The molecular weight of the enzyme from both organs was estimated as 60,000 +/- 5000. 6. Divalent metal ions increased the activities of both enzymes, with maximum catalytic activity in the presence of Mn2+ ions.

Abscesses in Crohn disease: percutaneous drainage.

Fifteen patients with Crohn disease underwent percutaneous catheter drainage of related abdominal abscesses. The abscesses were located in the right lower quadrant (five patients); in the quadratus lumborum and/or iliopsoas muscles (four patients); in the left paracolic gutter (two patients); and in the right gluteal muscles, the liver, the left subphrenic space, and the pelvis (one patient each). All abscesses were evacuated successfully (n = 15 of 15), and no patient required surgery for abscess drainage. Existing fistulas closed in four of seven patients; the other three patients underwent surgery for excision of diseased bowel and enteric fistulas. No patient developed an enterocutaneous fistula as a result of catheter drainage. Percutaneous abscess drainage is effective for abscesses related to Crohn disease and should be regarded as the procedure of choice. An operation for the abscess can be avoided, and early results suggest that bowel surgery may be obviated in selected patients.

Unsuspected pheochromocytoma: risk of blood-pressure alterations during percutaneous adrenal biopsy.

Four unsuspected pheochromocytomas were discovered during percutaneous fine-needle biopsy of the adrenal gland under ultrasound (n = 1) and computed tomographic (n = 3) guidance. One patient suffered an acute episode of alternating hypertension and hypotension during the procedure. A second patient had no alterations in vital signs during the procedure but had a severe hypertensive crisis during induction of anesthesia at surgery. Neither biopsy nor surgery affected the vital signs in the other two patients. During biopsy study of adrenal lesions, the possibility of unsuspected pheochromocytoma should be considered, and the interventional radiologist must be familiar with the emergency treatment of hypotensive or hypertensive crises that may occur.

Percutaneous cecostomy for decompression of the massively distended cecum.

Massive dilatation of the cecum developed in an elderly man following admission for an acute episode of upper gastrointestinal hemorrhage complicated by myocardial infarction, ventricular fibrillation, and pulmonary edema. A diagnosis of pseudo-obstruction was made. After an unsuccessful attempt at colonoscopy, percutaneous cecostomy was performed under computed tomographic guidance, using trocar technique. The cecal distention resolved and did not recur. Percutaneous cecostomy is an alternative to colonoscopy and to surgical cecostomy in the treatment of massive cecal distention.