Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes.

BACKGROUND: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022). METHOD: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data. RESULTS: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, p<0.001), more frequent oxygen administration (23% vs 12%, 10% and 5%, p = 0,001) and more symptomatic patients at the time of testing with Delta and WT (75% and 71%) versus Alpha and Omicron variants (55% and 66% respectively, p<0.01). Stillbirth tended to be associated with variants (p = 0.06): WT 1/231 (<1%) vs 4/126 (3%), 3/94 (3%), and 1/35 (3%) in Alpha, Delta and Omicron cases respectively. No other difference was found. CONCLUSION: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection.

Outcomes of functional treatment versus open reduction and internal fixation of condylar mandibular fracture with articular impact: A retrospective study of 83 adults.

INTRODUCTION: The treatment of fractures in the mandibular condylar process remains controversial. The aim of this study was to assess the outcomes of isolated functional treatment versus open reduction and internal fixation (ORIF) of mandibular condylar fracture with articular impact based on clinical and radiological criteria. MATERIALS AND METHODS: Eighty-three patients with a mandibular condylar fracture with articular impact were included in this retrospective study. They were divided according to Loukota, Spiessl and Schroll, Mercier and Rasse, Neff, and Hlawitschka classifications. Two groups were created: operated patients (operated) and non-operated patients (non-operated). Occlusal and functional features were evaluated using clinical measurements at 1, 3, 6, and 12 months after the treatment as well as radiological measurements performed preoperatively, 6 weeks later, and at the end of the follow-up. RESULTS: A male predominance was observed in the data (69.9%, P<0.0001). Isolated functional treatment was applied in 55 patients (66.26%). Twenty-eight patients (33.7%) were operated upon using a pre-auricular or modified Risdon's approach. Maximal mouth opening (MMO) was lesser in "operated" group compared to "non-operated" group until 6 months (25.75mm vs 31.96mm, 34.76mm vs 37.95mm, 38.06mm vs 41.87mm respectively 1, 3 and, 6 months, P<0.05). Results were satisfactory 1 year after treatment (41.29mm vs 45.22mm, P>0.05). There was no difference concerning temporo-mandibular joint dysfunctions between operated and non-operated patients. For unilateral fractures, the loss of height of the ramus was significantly higher in operated patients initially compared to "non-operated" group (P=0.0137). After surgical correction, there was no difference between the two sides of mandible. At the end of the follow-up, the there was no difference between operated and non-operated ramus (P=0.1304 and 0.6420). CONCLUSION: The present study showed that a properly followed isolated functional treatment provided similar clinical results to ORIF for mandibular condylar fractures with articular impact. Surgical treatment should be preferred when the loss of height of the ramus is severe to restore the ramus height since adult condylar remodeling is less efficient than in children.

[Intra- and interobserver reproducibility of the French version of the Constant-Murley shoulder assessment during rehabilitation after rotator cuff surgery]. / Etude de reproductibilité intra et inter-observateur de la version française du score de Constant au cours de la rééducation des coiffes opérées.

PURPOSE OF THE STUDY: The Constant-Murley scapular score is currently considered to be the gold standard for shoulder assessment in Europe. Few studies have examined the metrological qualities of this score. Our aim was to study the reliability and validity of the French version in a population undergoing reeducation after rotator cuff surgery. We wanted to determine how pertinent the score is during the reeducation phase (1-12 months after surgery). MATERIAL AND METHODS: Fifty-three patients volunteered to participate in this study. Shoulder assessment was performed by three observers. Intraobserver reproducibility was determined for 102 tests and two series of 32 and 56 tests were used to determine interobserver reproducibility. The internal coherence was studied on a sample of 61 tests. Three observers analyzed the apparent validity of the Constant Murley score. RESULTS: The correlations were satisfactory (intraobserver 0.96; interobserver 0.91 and 0.89 with the Spearman test) and sensitive (intraobserver 0.01; interobserver 0.07 and 0.01 with the Wilcoxon test). Despite satisfactory internal coherence (Cronbach alpha=0.75), the reproducibility of the overall score did not correspond necessarily to the reproducibility of the constituent scores. The measurement error might be related to patient- and observer-related interpretation variability. The apparent validity of the French version might be criticized for assessing rotator cuffs after surgery. CONCLUSION: A precise consensual protocol is needed for conducting the shoulder assessment and establishing the Constant-Murley score during the reeducation phase after rotator cuff surgery.

Cell culture of the mucinous variant of human colorectal carcinoma.

Two cell lines, RW-2982 and RW-7213, have been established for the first time from the mucinous variant of human colorectal carcinoma, which is a distinctive and important subtype that has a worse prognosis than the more common nonmucogenic large bowel carcinoma. Methods of establishment and observations made during 7 and 3 years, respectively, of continuous culture are described. These cell lines required 4-9 months of adaptation to tissue culture conditions before noticeable growth occurred. Both cell lines have the following unique properties: (a) growth in vitro as delicate branching three-dimensional tumor particles within a wide gel of insoluble, often translucent mucus (proteoglycan); (b) production of large quantities of carcinoembryonic antigen; (c) ability to survive or adapt to growth in media free of serum, hormones, growth factors, and all protein; and (d) tumorigenicity in multiple sites in nude mice, including liver, with especially rapid growth in the peritoneal cavity as gelatinous material that is nonadherent and noninvasive and thus resembles pseudomyxoma peritonei. Unlike other reported colorectal cell lines, these mucus-coated particulate cell lines will not readily grow as monolayers and grow much more slowly with a doubling time of 2 weeks or more. A serially transplantable tumor from the RW-7213 surgical specimen has also been maintained in nude mice since August 8, 1984. This tumor retains properties of the original specimen. Observations made on the tumor biology of mucogenic colorectal carcinoma using these cell lines are discussed.

Frequent loss of heterozygosity on chromosome 9, and low incidence of mutations of cyclin-dependent kinase inhibitors p15 (MTS2) and p16 (MTS1) genes in gliomas.

Four cyclin-dependent kinase inhibitors called p15, p16, p21 and p27 have been identified in mammals. Because these proteins participate in the control of cell cycle, they are potential targets for somatic mutations during carcinogenesis. In order to document the prevalence of p15 and p16 alterations in gliomas, we looked for loss of heterozygosity of chromosome 9p where these genes are localized. Allelic losses were observed in 31 of 44 investigated cases. In all cases they involved the p15/p16 locus. We then looked for mutations in the p16 and p15 genes in 46 gliomas. A total of three DNA variants were observed which were all present in the matched constitutional DNA. They may be unrelated to tumor development. A single somatic mutation was detected. It involved a C to G substitution in codon 93 of p16 and is predicted to change a threonine into an arginine. Taken together, these data indicate that inactivation by point mutation of these two cyclin-dependent kinase inhibitors is uncommon in glial tumor carcinogenesis, but that there may be a tumor suppressor gene on 9p in the vicinity of p16 and p15 genes.

Oncogene amplification in human gliomas: a molecular cytogenetic analysis.

Nine cases of malignant gliomas were selected for the presence of double minutes (dmin) or homogeneously staining regions (hsr) detected by conventional cytogenetics. Analyses were performed on fresh (2 cases) or xenografted (5 cases) tumors or both (2 cases). A modified comparative genomic hybridization technique (mCGH) was applied exhibiting a single amplified locus in 8 tumors and 4 amplified loci in one tumor. Recurrent sites of amplification were detected in 7p11-p12 (5 cases) and 1q32.1 (2 cases). Signals were also observed in 4q11-q12, 5p15.1, 7q31, 8q24.1 and 9p2 in one tumor each. Southern blotting demonstrated that the genes for EGFR (epidermal growth factor receptor), PDGFRA (platelet derived growth factor receptor alpha), MET and MYC oncogenes were involved in 7p11-p12, 4q11-q12, 7q31 and 8q24.1 amplifications, respectively. These amplifications were found by in situ hybridization on tumor spreads, in dmin or episomes for EGFR, dmin for PDGFRA and MET, and hsr and dmin for MYC genes. Other mCGH signals, for which no target genes could be proposed, were confirmed by chromosome paintings on tumor metaphases. In one of the tumors, the coamplification of DNA from 5p15.1 and 9p2 bands in the same dmin was demonstrated.

Effect of aminoglycosides on the disposition of thyroid hormones and thyroglobulin.

Our study was designed to confirm the potential effects of three aminoglycosides on the disposition of thyroid hormones. Twenty-seven patients diagnosed with either cellulitis (n = 19), chronic osteitis (n = 4), or an abscess (n = 4) were selected. Thirteen patients received tobramycin, 60 to 100 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; seven patients received netilmicin, 40 to 120 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; and seven patients received either cloxacillin, 1.5 gm iv q. 4 h., or cefoperazone, 2 to 4 gm iv q. 12 h. for at least 7 days. Another group of six normal subjects received neomycin, 0.5 gm po q. 6 h. for 7 days. All these subjects had normal thyroid function before antibiotic dosing and none had thyroid function abnormalities. Tobramycin and cloxacillin/cefoperazone did not influence thyroid function. Netilmicin decreased the total serum concentrations of triiodothyronine (T3) from 114 +/- 9 to 75 +/- 7 ng/dl (P less than 0.01), probably because of increased clearance, as the T3 free fraction increased from 0.43% +/- 0.02% to 0.49% +/- 0.02% (P less than 0.05). Thyroxine (T4) and reverse T3 (rT3) levels were not affected. Neomycin decreased T3 levels from 104 +/- 8 to 92 +/- 7 ng/dl (P less than 0.05) and the serum concentrations of thyroglobulin from 17.3 +/- 2.0 to 11.7 +/- 2.0 ng/ml (P less than 0.001). Because T4 and rT3 levels did not change, our results suggest that neomycin may have directly affected the gland. We conclude that some aminoglycosides can alter the disposition of thyroid hormones.

Intrathecal synthesis of the anti-Hu antibody in patients with paraneoplastic encephalomyelitis or sensory neuronopathy: clinical-immunologic correlation.

We studied the intrathecal synthesis of the anti-Hu antibody (also called type 1 antineuronal nuclear autoantibody) in 14 patients with isolated paraneoplastic subacute sensory neuronopathy (SSN) and 16 with paraneoplastic encephalomyelitis (PEM). Patients with PEM had higher anti-Hu titers in the CSF (p = 0.003) but not in the serum than those with SSN. Only one patient (7%) with SSN had a positive intrathecal anti-Hu antibody synthesis whereas this was present in 14 (88%) of the 16 patients with PEM (p < 0.0001). The correlation between the intrathecal production of anti-Hu antibodies and PEM supports the role of autoimmune mechanisms in the pathogenesis of PEM. The absent intrathecal synthesis of anti-Hu antibodies in patients with SSN suggests easier accessibility of the systemic immune reaction to the sensory neurons probably due to the partial absence of blood-nerve barrier in the dorsal root ganglia.

Primary central nervous system lymphoma: treatment with chemotherapy and radiotherapy.

Between 1989 and 1993, 22 HIV negative patients with primary central nervous system lymphoma (PCNLS) were treated with three different regimens. In group A, 13 patients received preradiotherapy systemic and intrathecal methotrexate (MTX), radiotherapy (RT) and three courses of post-RT chemotherapy (CT) with thiotepa and procarbazine. In group B, 4 patients received a similar CT only after RT and without intrathecal MTX in 3/4 cases. In group C, 5 elderly patients received CT alone. In group A, 9/13 patients achieved response after pre-RT CT and 12/13 were in complete response (CR) after RT. After a median follow-up of 27 months, 8/13 (62%) patients are alive but 4 have leucoencephalopathy and cognitive dysfunction. In group B, all 4 patients were in CR after RT but the 3 patients who did not receive intrathecal MTX died within 10 months with meningeal recurrence. In group C, 4/5 patients had a response to CT. 2 patients died of recurrent tumour at 5 and 10 months, and 2 are living in CR 11+ and 21+ months after diagnosis, 1 after salvage CT. Combined treatment with RT and CT is useful in PCNSL but adequate treatment of the meninges is required. CT alone is sometimes of value in elderly patients in whom RT is not indicated.

Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study.

Thirty-six patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of ifosfamide, carboplatin and etoposide (ICE) at tumour progression. Carboplatin and etoposide were both given at a dose of 75-100 mg/m2/day for 3 days, whereas ifosfamide doses ranged from 750 mg/m2/day to 1500 mg/m2/ day for 3 days, according to haematological tolerance. Treatment was repeated every 4 weeks. A minimum of three courses was required to evaluate the response unless the patient had rapid tumour progression. Grade III and IV haematological toxicity occurred in 15 patients (42%) and was lethal in one patient. Grade II hepatic toxicity was observed in one patient. Five complete (CR) and five partial responses (PR) were noted. 9 patients had stable disease (SD) after a minimum of three courses. CR + PR + SD was 53% (19/36). The median time to tumour progression (MTTP) was 13 weeks. Median survival (MST) was 29 weeks (44 weeks for R + S patients and 17 weeks for patients with progressing disease). This study suggests that the ICE combination is active in recurrent supratentorial malignant gliomas after failure of surgery, radiation therapy and chemotherapy, but at the cost of substantial haematological toxicity.

Multiple infusions of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (EMD 55,900) in patients with recurrent malignant gliomas.

In a prospective phase I/II trial, EMD 55,900, a murine monoclonal antibody (MAb) directed against EGF receptor, was administered at tumour recurrence to 16 patients previously treated with surgery, radiotherapy and chemotherapy for high grade supratentorial gliomas (11 glioblastomas, five anaplastic astrocytomas). Duration of treatment was planned for at least 4 weeks. The first 10 patients received 40 mg of MAb three times per week (median cumulative dose, 760 mg) and the last 6 patients received 200 mg three times per week (median cumulative dose, 2400 mg). Serum levels of EMD 55,900 were proportional to the injected dose. Repeated infusions of EMD 55,900 were well tolerated. In 13/16 patients, there were no adverse events. Among the 3 others, one had a grade IV neutropenia, one had a clinically asymptomatic hepatitis, and one had a skin rash. This last patient was the only one who had increased human antimouse antibodies (HAMA). After 4 weeks of therapy, 13 patients were evaluable for response. No measurable tumour regression was obtained with either schedule. 6 of the 13 patients (46%) showed evidence of progressive disease, while 7/13 (54%) had stable disease. All patients had progressive disease by 3 months. In this study, repeated infusions of EMD 55,900 were well tolerated but no therapeutic benefit was demonstrated.

Measles virus and Guillain-Barré syndrome during long-term hemodialysis.

In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state.

Hepatitis B antigen-associated periarteritis nodosa in patients undergoing long-term hemodialysis.

Periarteritis nodosa was observed in three of 266 persistent hepatitis B antigen (HBsAg) carriers undergoing long-term hemodialysis; no cases of necrotizing vasculitis occurred among 384 other patients undergoing dialysis having either no or transient antigenemia. Circulating e antigen, but no e antibody, was found in two of these three patients. The serum level of the third component of complement (C3) was normal in two patients and low in the third. Circulating immune complexes were demonstrated in all three patients, using polyethylene-glycol (PEG) precipitation, PEG-C4, and solid phase C1q tests. HBsAg and anti-hepatitis B antibody (HBsAb) were identified in the PEG precipitates using radioimmunoassay and electron microscopy technics. Direct immunofluorescence performed on a muscle biopsy specimen from one patient was positive for HBsAg, but not for immunoglobulin G (IgG), immunoglobulin M (IgM), C3 or C1q. These data support the hypothesis that circulating immune complexes involving HBsAg may be involved in the pathogenesis of periarteritis nodosa.

A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results.

PURPOSE: To evaluate the effects of limited field conventional cerebral radiotherapy (RT) on cognitive functions of adults. METHODS AND MATERIALS: A prospective neuropsychological study was performed on 17 patients who underwent conventional limited field RT for a low-grade glioma or for a good-prognosis anaplastic glioma. Results were compared with 14 control patients with low-grade gliomas who did not receive radiotherapy. RESULTS: A transient significant decrease of performances for the Reaction Time test was observed at 6 months in the irradiated group with return to baseline values 12 months post-RT. Subsequently, no other significant changes were observed over a 48-month follow-up period in the irradiated and nonirradiated groups. Nonetheless, when the scores of each patient were considered over time instead of the mean values of the group, one irradiated patient (5.8%) experienced progressive deterioration while two irradiated patients (11.7%) experienced long-lasting improvement. Individual changes did not occur in the control group. CONCLUSION: This study suggests that a transient early delayed drop of neuropsychological performances at 6 months is frequent following limited field conventional RT, but the risk of long-term cognitive dysfunction after irradiation is low, at least in the first 4 years after RT and when it is administered alone in young adults.

Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Analysis of oncogene expression in primary human gliomas: evidence for increased expression of the ros oncogene.

Expression of a panel of oncogenes and potential oncogenes was studied in normal human brain and in 17 human gliomas, including three low- and 14 high-malignancy-grade tumors. PolyA RNA was isolated from glioma biopsies and used as template for reverse transcriptase-catalyzed synthesis of radioactively labeled cDNA. Labeled cDNA was then hybridized to filters to which probes for various oncogenes had been attached. Increased signal intensity, as compared with that of normal brain, was observed for the ros oncogene in six of 17 gliomas, including gliomas of both low and high malignancy grades. Increased ros expression was verified by Northern blot analysis in one tumor. These results suggest that increased ros expression may play a role in tumorigenesis in a significant proportion of gliomas. Increased expression of other genes, including the erbA2, mel, and ets oncogenes was observed in a smaller proportion of the gliomas tested, suggesting a possible role for these oncogenes in individual tumors but no generalized role in development or progression of human gliomas.

Loss of heterozygosity on chromosome 22 in human gliomas does not inactivate the neurofibromatosis type 2 gene.

The molecular genetic alterations that underlie development of gliomas, the most common neoplasm of the human central nervous system, include activation of cellular proto-oncogenes as well as inactivation of tumor suppressor genes. Although research has identified some affected loci, others clearly remain to be identified. We have investigated loss of heterozygosity on chromosome 22 in a panel of sporadic gliomas, and have assessed the possibility that inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene on 22q plays a role in development of sporadic gliomas in humans. Loss of heterozygosity for loci on chromosome 22 loci was observed in 15 of 47 informative blood-tumor pairs, although no common area of loss of heterozygosity shared by all of these tumors could be identified. The most frequently affected segment, distal to the NF2 locus and bounded proximally by D22S15 and distally by a gene for myoglobin, was shared by as many as 11 tumors. Loss of heterozygosity at the NF2 locus was observed in 10 tumors. No rearrangements of the NF2 gene could be detected by Southern analysis of restriction endonuclease-digested genomic DNA, and no abnormally migrating bands were detected on single strand conformation analysis of individual exons of the NF2 gene. Thus, although frequent loss of heterozygosity on chromosome 22 suggests that inactivation of a tumor suppressor gene on this chromosome plays a role in development of gliomas, there is no evidence that inactivation of the NF2 gene is implicated in this process, confirming the results of other studies of the NF2 gene in human gliomas. The identity of the putative tumor suppressor gene on 22q involved in development of gliomas remains unknown.

A cytogenetic study of 19 recurrent gliomas.

A cytogenetic analysis was performed on 19 recurrent gliomas all of which had been treated by radiotherapy. All cases exhibited clonal chromosomal anomalies, the tumors were classified into four categories in relation to their mono- or polyclonality and to the presence or absence of a clonal evolution. Polyclonal tumors without clonal evolution had a delay of recurrence significantly longer than monoclonal or polyclonal tumors with clonal evolution. This difference could be related to the presence of clones with different malignant potential, which could be differentiated by their pattern of chromosomal aberrations. The malignant potential of "highly malignant" clones resulted from the juxtaposition of imbalances, such as monosomy 10, as in high-grade primary gliomas, and presumably radiation-induced structural rearrangements. That of clones of low malignancy was almost limited to the presence of multiple balanced structural rearrangements, probably induced by radiation.

Experimental carcinomatous plexopathy.

To understand the pathophysiology of carcinomatous plexopathy better, we studied nerve lesions induced by an experimental thyroid carcinoma implanted over the brachial plexus in 30 Fisher rats. We performed a morphological study including light and electron microscopic examination and teased fibre preparations of brachial plexuses from implanted and control animals. The control side was normal in all. A large tumour always grew within 2 months in all implanted animals and a third of the rats eventually developed weakness of the corresponding anterior limb extremity. On gross examination the tumour always surrounded the brachial plexus, which showed a variety of microscopic abnormalities, ranging from isolated endoneurial oedema to total degeneration of nerve fibres in 41% of the implanted rats. The most frequent lesions consisted of segmental demyelination associated with endoneurial oedema at the site of compression. Some axons degenerated distally and regeneration by sprouting of the proximal stump was noted 80 days after implantation. All subpopulations of nerve fibres were equally affected. Invasion of the intrafascicular area by the tumour was an uncommon finding, in comparison with the constant entrapment of the branches of the plexus by the tumour. This invasion by the tumour induced demyelination of nerve fibres at the site of compression, and sometimes at a distance from the tumour. Regeneration did not occur when the tumour had invaded the intrafascicular area.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of malignant gliomas and brain metastases in adults using a combination of adriamycine, VM 26, and CCNU. Results of a type II trial.

Forty-three patients with inoperable and/or recurring malignant gliomas and 30 patients with multiple recurring brain metastases were treated with a combination of adriamycine (45 mg/m 2 and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m 2 for 2 days) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso-urea (CCNU) (60 mg/m 2 for 2 days). These cycles of treatment were repeated as soon as the hematologic restoration was complete. The treatment was well-tolerated and the clinical condition of 31 out of 43 glioblastoma patients improved during the 2 months after the beginning of the treatment. Six out of eight patients with breast cancer metastases, one out of 13 with bronchial cancer metastases, and three out of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results reveals the following characteristics: 1. A low degree of efficiency of this combination in the treatment of brain metastases, except for breast cancer metastases. 2. Absence of complete correlation between the clinical results observed and the cinegammagraphic developments 3. Similarity of the results independent of the initial localization 4. Establishment of a 6-month median survival period, with ten patients at present in a state of apparently complete remission, 180-506 days after beginning of the treatment.