Malignant monstrocellular brain tumours

A series of 42 cases of monstrocellular brain tumour (MBT) who received surgery over a 34 year period is reviewed with the aim of gaining more understanding of the biology of this oncotype. A case of benign pleomorphic xanthoastrocytoma was identified among the cases and is discussed in another paper. In this series, as in most others taken from the literature, MBTs were more frequent in young subjects (55% were under 50 years of age and 17% were children) and presented as a superficially located (63%), often sharply circumscribed (42%) mass. The mean survival time for 24 patients treated by surgery and radiotherapy (RT) was 57 weeks compared to 32 weeks for 12 treated by surgery alone (p less than 0.02). Patients younger and older than 50 years showed the same survival and the slightly better course of children did not reach statistical significance. Besides postoperative RT, the only other factor that showed a significantly positive influence on survival was the presence of a definite lymphocytic infiltration (LI) in the tumour (p less than 0.05). This result confirms our previous study on the prognostic influence of LI in glioblastoma (GB). Actually, we noted that the prolonged survival of both MBT and GB patients exhibiting a definite LI (67% and 11.5%, respectively, in the two series) was strikingly similar. We conclude that MBT is a peculiar oncotype with a probably better prognosis than GB in the majority of cases. Lymphocytes seem to play a major prognostic role and giant-monstrous cells are indirectly implicated, reasonably enhancing the host's immune response by magnifying the antigenic stimulus.     

Ununited diaphyseal forearm fractures with segmental defects: plate fixation and autogenous cancellous bone-grafting

BACKGROUND: With current techniques of plate-and-screw fixation, diaphyseal nonunions of the radius and ulna are unusual. The few reports that have been published have discussed the use of structural corticocancellous bone grafts for the treatment of atrophic nonunions that are associated with osseous defects. We reviewed the rate of union and the functional results in association with the use of plate-and-screw fixation and autogenous cancellous (nonstructural) bone grafts. METHODS: Thirty-five patients with an atrophic ununited diaphyseal fracture of the forearm were treated with 3.5-mm plate-and-screw fixation and autogenous cancellous bone-grafting. A segmental osseous defect with an average size of 2.2 cm (range, 1 to 6 cm) was present in each patient. Twenty of the original fractures had been open. Eleven patients had had treatment of a deep infection before referral to us. The nonunion involved both forearm bones in eight patients, the radius alone in sixteen patients, and the ulna alone in eleven patients. RESULTS: The atrophic nonunion was associated with an open fracture in twenty patients, suboptimal fixation in twenty-two, a fracture-dislocation of the forearm in nine, and infection in eleven. All fractures healed without additional intervention within six months. Two patients had a subsequent Darrach resection of the distal part of the ulna for the treatment of arthrosis of the distal radioulnar joint. After an average duration of follow-up of forty-three months, the final arc of motion averaged 121 degrees in the forearm, 131 degrees at the elbow, and 137 degrees at the wrist, with an average grip strength of 83% compared with that of the contralateral limb. According to the system of Anderson and colleagues, five patients had an excellent result, eighteen had a satisfactory result, eleven had an unsatisfactory result (because of elbow stiffness related to associated elbow injuries in three and because of wrist stiffness in eight), and one had a poor result (because of malunion). CONCLUSIONS: When the soft-tissue envelope is compliant, has limited scar, and consists largely of healthy muscle with a good vascular supply, autogenous cancellous bone-grafting and stable internal plate fixation results in a high rate of union and improved upper limb function in patients with diaphyseal nonunion of the radius and/or ulna.     

Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum

The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here we show in a model of Brucella abortus infection of murine bone marrow-derived macrophages that a fraction of the bacteria that survive an initial macrophage killing proceed to replicate in a compartment segregated from the endocytic pathway. The maturation of the Brucella-containing vacuole involves sustained interactions and fusion with the endoplasmic reticulum (ER), which creates a replicative compartment with ER-like properties. The acquisition of ER membranes by replicating Brucella is independent of ER-Golgi COPI-dependent vesicular transport. A mutant of the VirB type IV secretion system, which is necessary for intracellular survival, was unable to sustain interactions and fuse with the ER, and was killed via eventual fusion with lysosomes. Thus, we demonstrate that live intracellular Brucella evade macrophage killing through VirB-dependent sustained interactions with the ER. Moreover, we assign an intracellular function to the VirB system, as being required for late maturation events necessary for the biogenesis of an ER-derived replicative organelle.     

Corticotropin-releasing factor concentrations exhibit an apparent diurnal rhythm in hypothalamic and extrahypothalamic brain regions: differential sensitivity to corticosterone

Regional brain concentrations of corticotropin-releasing factor (CRF) exhibited marked differences in a number of regions depending upon the time of day rats were sacrificed. When compared with animals killed at 09.00 h, CRF concentrations at 15.30 h were elevated in the median eminence, hypothalamus minus median eminence, preoptic area/suprachiasmatic nucleus, bed nucleus of the stria terminalis, septum, frontal/parietal cortex, cerebellum, cingulate cortex, locus ceruleus and the nucleus of the solitary tract. Animals that received 7 days of continuous corticosterone supplementation via osmotic minipump either did not exhibit an afternoon rise in CRF concentrations (median eminence, cingulate cortex and locus ceruleus) or exhibited significantly attenuated afternoon increases in CRF concentrations (hypothalamus minus median eminence). In rats killed at 09.00 h, corticosterone reduced CRF concentrations in the median eminence. Chronic corticosterone exposure did not affect CRF concentrations in any of the extrahypothalamic brain regions studied in rats killed at 09.00 h. These results suggest that a number of CRF-containing neurons in both hypothalamic and extrahypothalamic brain regions presumably undergo diurnal changes in their activity as evidenced by changes in CRF concentrations. Furthermore, chronic corticosterone supplementation can alter these changes, particularly those in the endocrine hypothalamus.     

Factors influencing ventilatory muscle recruitment in patients with chronic airflow obstruction

Patients with chronic airflow obstruction (CAO) frequently develop abnormal thoraco-abdominal excursion, but the patterns described are inconsistent and the factors that relate to their development remain unknown. We studied 45 stable patients with FEV1 ranging from 0.36 to 2.1 L. A pattern of ventilatory muscle recruitment (VMR) was established by simultaneously measuring gastric (Pg) and pleural (Ppl) pressures and rib cage (Vrc) and abdominal (Vab) volume displacement with inductance plethysmography. From these tracings, Pg-Ppl plots were constructed and the delta Pg/delta Ppl values were calculated. The delta Pg/delta Ppl was validated in 15 patients with simultaneous analysis of Vab-Pg plots. Pearson's test and multiple regression analyses were used to correlate delta Pg/delta Ppl to factors thought to influence respiratory muscle function such as age, sex, nutritional status (weight/height, albumin), hyperinflation, airflow obstruction, and arterial blood gases. We found a direct correlation between a more positive delta Pg/delta Ppl value and increasing hyperinflation (r = 0.69, p less than 0.0001), increasing airflow obstruction (r = -0.55, p less than 0.001), and decreasing diaphragmatic strength (r2 = 0.32, p less than 0.001). We also found that expiratory Ppl became more positive with decreasing FEV1 (r2 = 0.33, p less than 0.001). This change in VMR was independent of age, sex, nutritional status, and arterial blood gas determinations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interferon beta treatment: Bioavailability and antiviral activity in multiple sclerosis patients

Viral infections have been appointed as the main component of environmental susceptibility to multiple sclerosis (MS). Interferon beta is an immunomudulatory treatment that is able to modify the natural course of the disease; nonetheless, its mechanism of action in not well established yet. The objectives of the present study were (1) to evaluate the bioavailability of interferon beta through the measurement of the expression of myxovirus resistance protein (MxA), metalloproteinase 9 (MMP-9), and its inhibitor (TIMP-1); (2) to analyze its antiviral efficiency through the measurement of human herpesvirus-6 (HHV-6) prevalence; and (3) to correlate both parameters (bioavailability and antiviral efficiency) with the relapse rate in multiple sclerosis (MS) patients treated with interferon beta. Pairs of blood and serum samples were collected from 54 MS patients during five visits in 1 year: one before the start of the treatment and four during interferon beta treatment. Expression of MxA, MMP-9, and TIMP-1 was analyzed by quatitative real-time polymerase chain reaction (qRT-PCR) and HHV-6 genomes were detected by qPCR. The results showed a correlation between MxA and relapse rate (P = .014). MMP-9/TIMP-1 ratio was increased among the patients with relapses, and decreased among the relapse-free patients, although differences were not statistically significant. Furthermore, our results suggest a possible role for HHV-6 in MS, because 42.8% of patients with viral reactivations experienced at least one relapse versus 22.5% of patients without viral reactivations. Lastly, regarding the antiviral effectiveness of the interferon beta, the HHV-6 prevalence decreased from 58% to 36% in PBMCs and from 18.5% to 12.2% in sera; furthermore, a good correlation with the bioavailability of interferon beta was found, because patients with a decrease in HHV-6 prevalence had higher levels of MxA (P = .046, at the third month).