Adverse obstetric outcomes at term after hysteroscopic metroplasty.

STUDY OBJECTIVE: To estimate obstetrical complications at term after hysteroscopic metroplasty for septate uterus. DESIGN: A retrospective comparative study (Canadian Task Force classification II-2). SETTING: La Conception Hospital, Department of Obstetrics and Gynecology, Marseille, France. PATIENTS AND INTERVENTIONS: Thirty-one women who had a term pregnancy from January 1996 through December 2004 after hysteroscopic metroplasty for septate uterus (group A) were studied retrospectively. A control group (group B) of 62 women was selected from the same database who had term pregnancies and no history of hysteroscopic metroplasty. MEASUREMENTS AND MAIN RESULTS: Obstetric complications at term and neonatal outcomes after hysteroscopic metroplasty were compared between 2 groups. The rate of fetal malpresentation was significantly higher in group A versus group B (11/31 [35.5%] vs 0/62, p < .001). Mean birth weight was significantly lower in group A versus group B (2940 g +/- 52 vs 3266 g +/- 456, p =.002). The rate of caesarean section was significantly higher in group A versus group B (19/31 [61.3%] vs 4/62 [6.4%], p < .001). CONCLUSION: The results of this study suggest that patients with a previous hysteroscopic metroplasty for septate uterus are at increased risk for fetal malpresentation at term, low birth weight infants, and delivery by caesarean section and should therefore be informed of these risks before delivery.

[Neoadjuvant chemotherapy for symptomatic non operable grade II fibrillary astrocytoma in adults]. / Chimiothérapie néoadjuvante dans les astrocytomes fibrillaires de grade II symptomatiques non opérables de l'adulte.

We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated.

Temozolomide chemotherapy in recurrent oligodendroglioma.

The authors determined the tolerance, response rate, and duration of recurrent anaplastic oligodendroglioma in 30 patients to temozolomide given orally at 150 to 200 mg/m2 on days 1 through 5 in cycles of 28 days. Nine patients responded: 7 of 27 patients (26%) treated with temozolomide after prior PCV chemotherapy and 2 of 3 chemotherapy-naive patients (both complete response). Median time to progression in responding patients was 13 months. Temozolomide shows promise and has an acceptable safety profile in recurrent anaplastic oligodendroglial tumors. Patients not responding to PCV may respond to temozolomide.

Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients.

We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28-82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay +/- SD 6.5 +/- 7.0 months; range 0.1-47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62-12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05-2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12-2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08-2.40), and absence of treatment (RR 2.56; 95% CI 1.76-3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.

Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies.

The outcome of 34 women with anti-Yo-associated paraneoplastic cerebellar degeneration was reviewed. Three patients had not developed cancer after more than 4 years of follow-up. The only independent predictor for survival was the type of associated tumor (risk ratio, 1.79; 95% CI, 1.02 to 3.12). Median survival was 100 months for patients with breast cancer and 22 for those with gynecologic cancer. Although paraneoplastic cerebellar degeneration leads to the diagnosis of cancer in 63% of the patients, cancer progression was the cause of death in 52%.

Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone.

OBJECTIVES: To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). METHODS: Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n = 10) or cerebellar degeneration (PCD) with anti-Yo Abs (n = 7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS< or =3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS> or =4). RESULTS: Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS> or =4, none improved. Of the nine patients with RS< or =3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. CONCLUSIONS: This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.

Second line chemotherapy with docetaxel in patients with recurrent malignant glioma: a phase II study.

The objective of the study was to assess the efficacy of docetaxel in recurrent supratentorial malignant gliomas. The sample size of the study was determined by the Gehan's method for a response rate of 20% and a beta error of 5%. In the first step 14 patients (age 27-69, median 50; Karnofsky index 50-90, median 75) with recurrent malignant glioma after surgery, radiotherapy and nitrosourea, were enrolled (12 glioblastomas, 2 anaplastic astrocytomas). Docetaxel at the initial dose of 80 mg/m2 was administered every 3 weeks until progression or unacceptable toxicity. A total of 41 cycles was administered. Patients received a median of two cycles (range 1-6). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was terminated. Two stabilizations were observed (14 and 15 weeks). Median TTP was 7 weeks (44 days). Median overall survival from recurrence was 26.5 weeks (6.4 months). Grade 3-4 neutropenia was observed in 8 patients (57%) but no life-threatening toxicity was observed. Other toxicities were uncommon and mild. Dose reduction was performed in 5 patients. This study suggests that docetaxel displayed no significant activity in patients with malignant recurrent gliomas.

Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor.

OBJECTIVE: To evaluate 1) the effect of the tumor treatment on the clinical course of paraneoplastic encephalomyelitis (PEM) with anti-Hu antibodies, 2) the impact of immunotherapy on the tumor evolution, and 3) the outcome of the small cell lung cancer (SCLC) of PEM patients compared with that of patients without PEM. METHODS: The authors retrospectively analyzed 51 PEM patients (42 with SCLC, 9 with other tumors) who received antineoplastic treatment with (25 patients) or without (26) concomitant immunotherapy. Tumor response was assessed at the end of the antineoplastic treatment. Progression of PEM was defined as a change of at least 1 point in the Rankin scale measured at the onset and at the end of the tumor treatment. To evaluate the outcome of SCLC, 27 PEM patients with SCLC were matched one-to-one with SCLC patients without PEM for age, performance status, tumor stage, and type of antineoplastic treatment. RESULTS: Thirty-six (70%) patients were neurologically stable at the end of the tumor treatment. In a logistic regression analysis, tumor complete response was the only predictor of PEM stabilization (OR 7.07; 95% CI 1.68 to 29.76; p = 0.006). Immunotherapy did not modify the outcome of the tumor and PEM. Median survival was similar in SCLC patients with and without PEM, but the probability of survival at 30 months was higher in PEM patients with SCLC (OR 5.26; 95% CI 1.0004 to 27.6902; p = 0.03). CONCLUSIONS: Complete response of the tumor seems to have a favorable influence on the course of paraneoplastic encephalomyelitis (PEM). Concomitant immunotherapy does not adversely affect the tumor outcome. The small cell lung cancer of PEM patients may have a slightly better evolution than that of patients without PEM.

Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study.

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p < 0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p < 0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.

Neurological complications of radiotherapy and chemotherapy.

Neurological complications of radiotherapy and chemotherapy can affect the central or peripheral nervous system. Most are dose-dependent and constitute a limiting factor in the administration of treatments. Radiation-induced neurological complications are classified as acute, early-delayed or delayed. The most important are radionecrosis and cognitive dysfunction/leukoencephalopathy. Neurotoxicity of chemotherapy is frequent and depends upon dose, type of drugs (especially cisplatin and methotrexate) and their combination with radiotherapy.

Inhibition of graft-versus-host reaction by treatment of immature thymocytes with eicosanoids.

A model of in vivo secondary graft-versus-host (GVH) was used to appraise the behaviour of allostimulated eicosanoid-treated thymocytes. During the first step of the experiment P1 immature parental thymocytes were preincubated in the presence of P2 allogenic mature lymphocytes and eicosanoids (either PGE2 or LTB4). During the second step, the preincubated cells were injected intravenously into P1xP2 F1 irradiated hybrids and the in vivo mixed lymphocyte reaction assessed by 3H-thymidine uptake by the cells harboured in the spleen of the host. We also investigated the production of cytotoxic cells. We observed that PGE2 and LTB4 both influence the behaviour of immature thymocytes and that, in the context of allostimulation such as GVH, they induce a state of tolerance. The data are in agreement with a model of involvement of eicosanoids in education of thymocytes within the thymic organ.

NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.

[Biological diagnosis of malaria: dangers of the automated blood differential count]. / Diagnostic biologique du paludisme: dangers de l'automatisation de la formule sanguine.

Automated differential counting systems deprive laboratories of blood smear study and so malaria risks not to be diagnosed if plasmodium search is not prescribed by the physician. Some abnormalities (atypical lymphocytes called LUC and thrombopenia) can induce a blood smear. But a study of 96 patients shows that, during the first analysis, these abnormalities can miss for nearly a third of one's case. So it is very important to prescribe malaria search on blood smears when there is the least clinical symptom.

Effect of arachidonic acid metabolites on CR1 expression by B-lymphocytes.

The effect of arachidonic acid metabolites on the expression of the receptor for the C3b/C4b fragment of complement (CR1) by human B-lymphocytes was investigated. Kinetic experiments to determine CR1 expression over time indicated that the maximal receptor number occurred at 2 h, followed by a return to baseline values. Addition of 10(-4) M puromycin to the cells suggested that the increase was due to the expression of an intracellular pool and not de novo synthesis of new receptor molecules. B-lymphocytes were incubated with arachidonic acid, 15-hydroxyeicosatetraenoic acid, leukotrienes B4 or C4 or prostaglandin E2 (PGE2). The quantity of membrane antigenic binding sites was determined before and after incubation. The lipoxygenase metabolites did not alter CR1 numbers. In contrast, PGE2 significantly decreased (P less than 0.05) the quantity of CR1 expressed. In kinetic experiments, PGE2 blocked the maximal expression of CR1 seen at 2 h, indicating that it prevents the appearance of an intracellular pool of receptor. These results show that CR1 number on B-lymphocytes can be altered by at least one arachidonic acid metabolite. This may offer a partial explanation for the inhibitory effects of PGE2 on B-cell proliferation and immunoglobulin secretion since CR1 is implicated in B-lymphocyte differentiation and specific antibody response.

Effect of PGE2 and LTB4 on vicia villosa binding lymphocytes.

Since there is a good deal of evidence that vicia villosa lectin (VVA) binds to contrasuppressor cells, mouse splenocytes and thymocytes were sorted by binding to VVA-coated Petri dishes. It was observed that vicia villosa adherent cells (VVA(+)) did not proliferate when mitogens were added to cultures, but they did enhance the thymidine uptake of PHA or ConA stimulated vicia villosa non-adherent (VVA(-)) splenocytes. PGE2 treatment of VVA(+) splenocytes or VVA(+) immature thymocytes did not very much affect the VVA(+) cell behavior. On the other hand, LTB4 increased the enhancing capability of VVA(+) splenocytes. Therefore, investigations dealing with the effects of LTB4 on lymphocyte subsets which may include VVA(+) cells should take into consideration the possible presence of contrasuppressor cells.

[Tomodensitometric study of the course of supratentorial malignant glioma after treatment]. / Etude tomodensitométrique de l'évolution des gliomes malins sus-tentoriels après traitement.

Computed tomography now is the primary method for the management of supratentorial malignant gliomas. In this study, analysis of CT scan controls done at 2 or 3 month intervals in 87 treated patients showed that: 1) in most instances, recurrence arose within the initial tumor site; 2) the tumor invades contiguous anatomical structures through intra-and inter-hemispheric association fibers; 3) multicentric gliomas are uncommon (less than 6% of patients). The purpose of this study was to reduce irradiated volumes and thus radiation toxicity. The finding that most patients experience recurrence within the original tumor site is evidence experience recurrence within the original tumor site is evidence that current radiation doses and total brain irradiation are inappropriate. Our results are consistent with those recently reported in the medical literature. Using computed tomography data, it should be possible to restrict the irradiated volume to the tumor site and to presumptive extension pathways. Higher doses may be delivered to this volume.