Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies.

Although anti-CD20 monoclonal antibodies (mAbs) show promise for the treatment of chronic lymphocytic leukemia (CLL), the success of the anti-CD20 mAb rituximab in CLL treatment has been limited. Novel anti-CD20 mAbs with more potent cytotoxic activity have recently been engineered, but so far most have only been tested in vitro with natural killer (NK) cells from healthy donors. Because it is still unclear whether these optimized cytotoxic mAbs will improve NK-cell killing of tumor cells in CLL patients, we characterized the relevant phenotypic and functional features of NK cells from CLL patients in detail. Expression of inhibitory and activating NK-cell receptors and of Fc gamma receptor IIIA (FcγRIIIA) is well preserved in CD16(+)CD56(dim) cytotoxic NK cells from these patients, independently of disease progression. These cells are fully functional following cytokine stimulation. In addition, the FcγRIIIA-optimized LFB-R603 anti-CD20 mAb mediates 100 times greater antibody-dependent cell-mediated cytotoxicity by NK cells from CLL patients and healthy donors than rituximab. Enhanced degranulation against autologous B-CLL cells is observed at lower concentrations of LFB-R603 than rituximab, regardless of CLL prognostic factors. These findings strongly justify further clinical development of anti-CD20 mAbs optimized for FcγR engagement in CLL patients.

[Massive fetomaternal hemorrhage revealed by decreased perception of active fetal movements]. / Macrotransfusion foeto-maternelle spontanée révélée par une diminution de la perception des mouvements actifs foetaux.

Massive fetomaternal hemorrhage is rare. Without risk factors, early diagnosis is difficult to establish. The clinical and paraclinical manifestations are not specific and depend on fetal compensatory reactions; the Kleihauer test will confirm the diagnosis. Two cases of massive fetomaternal hemorrhage preceded by decreased fetal movements are presented here. An emergency delivery by cesarean section saved one child. Despite a favorable clinical and laboratory evaluation, one fetal death could not be avoided. Early diagnosis and specialised management are essential to improve prognosis. These observations indicate that it is mandatory to carry out a Kleihauer test whenever a decrease of fetal movements is observed.

[Endometrioid adenocarcinoma arising from adenomyosis. A case report and literature review]. / Adénocarcinome endométrioïde résultant de foyers d'adénomyose: à propos d'un cas et revue de la littérature.

In spite of many references to carcinoma arising from endometriosis, there are few documented cases in the literature of endometrioid adenocarcinoma developed in association with adenomyosis. We report a case of endometrioid adenocarcinoma arising from adenomyosis. Carcinogenic and prognostic factors as well as the therapeutic consequences of this unusual situation are discussed. The use of hormonal replacement therapy by patients with a prior history of adenomyosis is also examined.

[Contribution of Doppler ultrasound to the antenatal diagnosis of persistent right umbilical vein: case report]. / Apport des Dopplers couleur et pulsé dans le diagnostic anténatal de la persistance anormale de la veine ombilicale droite: à propos d'un cas.

We report a case of an isolated persistent right umbilical vein which was diagnosed on an ultrasound examination performed in the third trimester of pregnancy. This was made possible by the contribution of color flow Doppler and real-time ultrasound. Having isolated the anomaly no further fetal monitoring was instituted. Delivery was at term and the infant is doing well. Persistent right umbilical vein results from an anomaly of organogenesis. It represents the main intra abdominal anomaly of this vein. Its incidence is estimated at approximately 1 case for 500 antenatal ultrasound examinations. Ultrasonographic diagnosis is relatively easy and can be performed near the end of the first trimester. After insertion in the abdominal wall, the umbilical vein passes round the gallbladder from the right before connecting to the portal vein in the intra-hepatic form; right atrium, inferior vena cava, superior vena cava or iliac vein in extra-hepatic form. Diagnosis is affirmed by color flow Doppler, which emphasizes a continuity of blood flow between the extra and intra abdominal segment of the umbilical vein, and real-time ultrasound, which shows a venous blood flow. Prognosis depends essentially on the existence of congenital malformations, which are observed in 10 to 25% of cases. When isolated, persistent right umbilical vein is generally associated with favorable outcome and must be considered as a normal fetal anatomical variant.

[Placental chorioangiomas diagnosed during the second trimester of pregnancy: four cases]. / Les chorio-angiomes placentaires diagnostiqués au second trimestre de la grossesse.

Placental chorioangioma is a benign vascular tumor found in about 1% of pregnancies at routine histological examination of the placenta. The large placental tumor may cause serious fetal complications. We report 4 cases of placental chorioangioma diagnosed during the second trimester. Three pregnancies with rapidly growing tumors measuring more than 4 cm led to fetal hydrops and perinatal death despite thoracocentesis and cesarean delivery at 33 weeks (1 case) and repeated amniodrainage (1 case). The only surviving infant presented with a 3.3cm tumor which grew progressively to 8 cm at 38 weeks and did not induce polyhydramnios or hydrops. Although aggressive prenatal management of placental chorioangioma has been reported using amniodrainage, intrauterine transfusions, embolization, or ligation of the tumor vessel supply, prognosis remains poor for large tumors and largely depends on fetal hemodynamic tolerance.

[Anesthetic management of obstetrical labor in a parturient with muscular carnitine palmitoyl transferase deficiency]. / Prise en charge anesthésique du travail obstétrical chez une parturiente atteinte d'un déficit musculaire en carnitine palmitoyl transférase.

We report a case of a patient with carnitine palmityl deficiency in active labour. We discuss the metabolic and energetic implications of obstetrical labour in regard with the mitochondrial myopathy and we propose an optimal management. Neuroaxial analgesia and glucose infusion are indicated in early labour because it is necessary to alleviate stress and pain in order to avoid rhabdomyolysis associated with CPT deficiency. Combined spinal epidural analgesia using intrathecal opioid alone then epidural naropein should be a relevant choice because of a minimal motor blockage. Monitoring of myolysis using serum creatinine phosphokinase levels must take in account CK and MB fractions releases to the circulation during obstetrical labour.

[Antenatal diagnosis of limb body wall complex]. / Diagnostic anténatal du <>.

The "limb body wall complex" or LBWC is a rare polymalformative syndrome. Two distinct phenotypes of which were recently described: one form with "placento-cranial" adhesion and the other with "placento-abdominal" adhesion. Coelosomia is found in all cases, it variably coexists with encephalic, vertebral, visceral or limb anomalies. Three pathogenesis are proposed: the "early amnion rupture" theory and the "vascular" theory can explain the form with "placento-cranial" adhesion, conversely, the "defective folding process" allows for a better explanation of the form with "placento-cranial" adhesion. These theories do not exclude each other if we accept that this syndrome could be split: the first form would then be the original "LBWC" et could belong to "amniotic band syndrome", the mechanism of which is not precisely known, whereas the second could be named "body stalk syndrome" - "syndrome du cordon court". In any case, this syndrome should be better known so as to be studied and give a prognosis for a later pregnancy, because there is no recurrence.

[Abdominal colposacroplexy for the treatment of vaginal vault prolapse with or without urinary stress incontinence]. / La promonto-fixation par voie abdominale dans la cure des prolapsus génitaux féminins avec ou sans incontinence urinaire. A propos de 271 cas.

OBJECTIVE: The aim of this study was to assess the factors of success in abdominal colposacropexy (CSP) procedures. PATIENTS AND METHODS: We performed 271 consecutive CSP between 1986 and 1997 (mean age: 48.8 years +/- 11.1). We reviewed 217 patients (80.1%). Mean duration of follow-up was 5.5 years (1-136 months). We performed: 18 CSP with Goretex mesh, 3 with resorbable mesh and 196 with Mersilene; 179 CSP with posterior colporraphy and 38 without; 208 CSP with culdoplasty (Moschowitz's procedure) and 9 without; 182 CSP with anterior and posterior meshes, 26 with posterior mesh only and 9 with anterior mesh only. RESULTS: 97.7% (212/217) of patients were cured for prolapse. 58% (125/217) had urinary stress incontinence totally cured and 82% (178/217) had urinary stress incontinence improved. Rejected grafts were 16.7% (3/18) with Goretex mesh and 1.1% with Mersilene mesh (p = 0.004). Recurrent prolapses were 1.1% (2/196) with CSP with posterior colporrhaphy and 7.9% (3/38) in CSP without (p = 0.009; OR = 0.14, CI = 0.02-0.86); 4/208 with CSP with culdoplasty and 1/9 with CSP without (p = 0.04; OR = 0.17, CI = 0.02-1.58). Recurrent stress incontinence was observed in 4/9 cases with CSP with anterior mesh only and 28/182 with CSP with anterior and posterior meshes (p = 0.03; OR = 0.34, CI = 0.12-0.97). CONCLUSION: CSP must use anterior and posterior Mersilene mesh. The CSP must be systematically combined with posterior colporraphy and culdoplasty (Moschcowitz's procedure).

[Maternal and congenital syphilis]. / Syphilis maternelle et congénitale.

Testing for syphilis during pregnancy reveals a positive serologic status in 0.02% of cases. However, a 66% rate of stillbirths is noted in women who are infected and who have not benefited from any treatment. Routine screening is at present performed during the early stages of pregnancy but a second serologic test during the third trimester is useful in the diagnosis of a late infection especially in drug users or HIV (human immunodeficiency virus) positive patients. Congenital syphilis is diagnosed in utero when a positive maternal serologic status is associated with ultrasound images showing fetal abnormalities; these include hepatosplenomegaly, hyperechogenic bowel, signs of bowel obstruction or fetal hydrops. Maternal syphilis is treated by delayed action penicillin and is indicated even for patients allergic to the antibiotic which in this particular case is delivered after desensitization. First line therapy by intravenous penicillin is indicated when confronted with the following high risk factors of congenital syphilis: an elevated titre of VDRL (venereal disease research laboratory) at the time of diagnosis or delivery, unknown date of the precise onset of the infection, the appearance of a rash or of a chancre during pregnancy, ultrasound fetal abnormalities or late therapy during the third trimester. Treatment of the new-born child will depend on the results of clinical, serologic and X-ray evaluation. Long term follow-up for at least a year is mandatory.

[Malignant non-Hodgkins lymphoma manifested in an ovarian tumor. Five case reports]. / Lymphomes malins non hodgkiniens révélés par une tumeur ovarienne. A propos de 5 observations.

Five cases of non-Hodgkin malignant lymphoma (NHML) presenting as ovarian tumours are reported. All corresponded to disseminated lymphomatous disease, none was of low grade. Ultrasound showed a solid, most often homogeneous, hypoechoic, bilateral mass in 4 of 5 cases. Its association with many lymph nodes and mainly parenchymal localisation suggested of the NHML. Only histologic and immunohistochemical findings may provide the final diagnosis. The biopsy for those studies should be obtained as least invasively as possible because treatment of NHML is chemotherapy.

[Prenatal diagnosis of three caudal regression syndromes associated with maternal diabetes]. / Diagnostic anténatal de 3 syndromes de régression caudale associés à un diabète maternel.

We report three cases of caudal regression syndrome diagnosed in utero. Caudal regression syndrome (CRS) is a rare condition associating vertebral agenesia and urinary and digestive tract malformations. Pathogenesis is not clear but, as in our three cases, the CRS is often associated with poorly controlled maternal diabetes. Antenatal ultrasound examinations may reveal the disease in major forms with a non-viable foetus. In our 3 cases, a femoral "V" was associated with sudden interruption of the spine. Minor forms may not be recognized until childhood. Prognosis depends essentially on the extent of spinal involvement and associated malformations. Sirenomelus was considered for many years to be the most severe form of caudal regression, but recently acquired evidence suggests that these two conditions are separate entities.

[Value and limits of complementary investigations in cases of toxoplasmosis seroconversion during pregnancy. A case report and review of the literature]. / Intérêt et limites des investigations complémentaires en cas de séroconversion toxoplasmique en cours de grossesse. A propos d'un cas et revue de la littérature.

We report a case of acute toxoplasmosis during the first trimester of pregnancy in which antenatal diagnosis was negative. Except for non-specific signs of liver failure, assessment by repeated ultrasound scans, testing of fetal blood for toxoplasmic specific antibodies and competitive PCR to isolate the parasite, had ruled out fetal infection. In spite of early treatment with spiramycin, and although the infant was assumed to be non-contaminated, severe hydrocephalus was noted at 3 and half months of life, arising soon after therapy had been stopped. This case focuses attention on the problem of the shortcomings of the diagnostic techniques currently used, and leads us to question our practical course of action. Several questions are thus raised: how reliable are indirect signs of fetal compromise, what is the real sensitivity of the PCR test and how useful are repeated amniocentesis and inoculation of the amniotic fluid to mice.

[Steinert's disease and pregnancy. A case report and recent literature]. / Maladie de Steinert et grossesse. A propos d'un cas et des données récentes de la littérature.

Steinert's disease or myotonic dystrophy is a heredo-degenerative neuroendocrinal dystrophy. It is an autosomal dominant disorder. The arising of a congenital myotonic dystrophy of one of the new-born children of the maternity hospital enabled to diagnose the Steinert's disease of his mother. A review of the international literature enabled us to recall its interactions with pregnancy. There is an aggravation of myotonia and multiple obstetric complications such as miscarriage, premature onset of labor, polyhydramnios, stillbirth, difficulties during the evacuation, atonic postpartum hemorrhage, anesthetic-accidents. The congenital variant of myotonic dystrophy (6 to 30% of the cases) is a severe disease with a high mortality. It is only seen in the offspring of mothers who themselves have myotonic dystrophy. The myotonic dystrophy gene has been isolated and the mutation-causing myotonic dystrophy was found to result from a series of trinucleotide (CTG) repeats located in the 3' untranslated region of the gene. The direct diagnosis is henceforth possible both on the fetus and parents. Steinert's disease and its association with pregnancy are rare, especially when the affected parent has hypogonadism. The diagnosis of the congenital form is difficult because of the mother is unaware of the disorder. Family and personal history may give hints: hydramnios, appearance delay and reduced fetal movements, and the association at birth of generalized hypotonia with neonatal respiratory distress.

[Hydrocephalus with cerebrospinal fluid shunts and pregnancy: 2 cases]. / Hydrocéphalie appareillée et grossesse: 2 cas.

During pregnancy 50% of all cases with a ventriculo-peritoneal shunt malfunction. This is because of anatomo-physiological changes associated with the pregnant state, and shows itself as a rise in intracranial tension. There were no acute neurological complications at term; with the malfunction of the shunt distally, vaginal delivery is preferable. It is not necessary routinely to carry out instrumental delivery.

[Retrograde section of uterine septa under ultrasonic control]. / Section rétrograde de cloisons utérines sous contrôle échographique.

A new technique for the treatment of uterine septa is described. The septum is divided by the transcervical route, using 4 mm endoscopic scissors. Simultaneously, real-time ultrasonography confirms the diagnosis of septate uterus and ensures the safety of this blind procedure. Ultrasonic guidance also enables the septum to be divided along the medial antero-posterior plane and the distance between the upper limit of the section and the fundus uteri to be measured. The operation is rapid, carries a limited risk, leaves no uterine or abdominal scar and requires no special equipment. The elective indication for section of uterine septa is habitual abortion. This convenient method can also be used in women who have never been pregnant during coelioscopy for sterility or section of a vaginal septum.

[Endometrial biopsy and hysterography prior to IUD insertion (author's transl)]. / Bipsie d'endometre et hysterographie avant insertion des dispositifs intra-uterins.

PIP: With endometrial biopsy prior to insertion of IUD it is possible to detect about 25% of contraindications, especially endometritis, which is often present without any signs of genital infection. After observations on 290 patients the authors found that hysterosalpingography would still show anomalies gone undetected by normal biopsy. Such abnormalities as hydrosalpinx, cervical carcinoma, and uterine anomalies constitute definite contraindication to the use of IUD. After such assessment the authors were able to improve IUD retention on 280 insertions, obtaining a retention rate of 87% after 1 year of use. (Summary in ENG).^ieng

[The effect of amniofetography on the fetal thyroid (author's transl)]. / Incidence de l'amniofoetographie sur la thyroïde foetale.

Although there are certain advantages of amniofetography they must be considered against the risk of fetal hypothyroidism "in utero" with its prognostic danger. The authors report six case histories which illustrate this risk and they draw attention to the possible effect on the thyroid gland "in utero". Amniofetography should therefore be reserved solely for those cases in which the indications exist and there are no other possible means of diagnosis. If it is indicated means must be found of treating the possible transitory iatrogenic hypothyroidism.

[Danger of iodine drugs in the pregnant woman]. / Dangers des médicaments iodés chez la femme enceinte.

The authors draw attention to the fact that the possible effects of drugs containing iodine are often neglected during pregnancy. As an example, they report the following observation : "A young woman with benign asthma, treated for 14 years Asthmasedine and Asthmaligne, gave birth, on the 36th week of pregnancy, to a child apparenty dead but who was able to be reanimated. The child showed two types of signs : respiratory distress due to higher neurological disorders and a multinodular, non-compressing goiter. These two complications were caused by a congenital hypothyroidism corroborated by laboratory tests and due to the prolonged absorption of iodinated drugs by the mother". In conclusion, in cases of women receiving during pregnancy high doses of drugs containing iodine (250 such drugs are recorded in the Vidal), it is desirable to control the effect on the fetus and to propose an intra-amniotic therapy with L-Thyroxine, thus allowing a cerebral development close to normal.