Under-recognized toxicities of cranial irradiation.

Cranial irradiation of primary or metastatic lesions is frequent, historically with 3D-conformal radiation therapy and now with stereotactic radiosurgery and intensity modulation. Evolution of radiotherapy technique is concomitant to systemic treatment evolution permitting long time survival. Thus, physicians have to face underestimated toxicities on long-survivor patients and unknown toxicities from combination of cranial radiotherapy to new therapeutics as targeted therapies and immunotherapies. This article proposes to develop these toxicities, without being exhaustive, to allow a better apprehension of cranial irradiation in current context.

Analysis of envelope sequence variants suggests multiple mechanisms of mother-to-child transmission of human immunodeficiency virus type 1.

In order to elucidate the molecular mechanisms involved in human immunodeficiency virus type 1 (HIV-1) mother-to-child transmission, we have analyzed the genetic variation within the V3 hypervariable domain and flanking regions of the HIV-1 envelope gene in four mother-child transmission pairs. Phylogenetic analysis and amino acid sequence comparison were performed on cell-associated viral sequences derived from maternal samples collected at different time points during pregnancy, after delivery, and from child samples collected from the time of birth until the child was approximately 1 year of age. Heterogeneous sequence populations were observed to be present in all maternal samples collected during pregnancy and postdelivery. In three newborns, viral sequence populations obtained within 2 weeks after birth revealed a high level of V3 sequence variability. In contrast, V3 sequences obtained from the fourth child (diagnosed at the age of 1 month) displayed a more restricted heterogeneity. The phylogenetic analysis performed for each mother-child sequence set suggested that several mechanisms may potentially be involved in HIV-1 vertical transmission. For one pair, child sequences were homogeneous and clustered in a single branch within the phylogenetic tree, consistent with selective transmission of a single maternal variant. For the other three pairs, the child sequences were more heterogeneous and clustered in several separate branches within the tree. In these cases, it appeared likely that more than one maternal variant was responsible for infection of the child. In conclusion, no single mechanism can account for mother-to-child HIV-1 transmission; both the selective transmission of a single maternal variant and multiple transmission events may occur.

Erratic G-->A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus.

The complete nucleotide sequence of an integrated provirus of caprine arthritis-encephalitis virus (CAEV) has been determined. The provirus was defective due to extensive G-->A hypermutation. Rather than being a smooth phenomenon distributed throughout the genome it was highly erratic with hypermutated and normal regions being juxtaposed, probably reflecting local fluctuations in the intracellular dCTP pool during reverse transcription of the CAEV genome. The pattern of sequence variation within the surface glycoproteins differs subtly from that of the primate lentiviruses.

A case-control study of gastric cancer and nutritional factors in Marseille, France.

A case-control study was conducted in Marseille (France) to investigate the relationship between usual diet and risk of gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were identified in 8 major centres for gastric surgery. Controls were selected in specialized medical centres from patients undergoing functional reeducation for injuries or trauma, according to the age and sex distributions of the cases. The study involved 92 cases and 128 controls who were interviewed with a dietary history questionnaire on their usual diet during the year preceding first symptoms for cases, or preceding interview for controls. Odds ratios for specific foods were calculated after adjustment for age, sex, occupation and energy intake. A reduced risk was observed for consumption of raw vegetables (OR2: 0.55; OR3: 0.41 for the second and third tertiles, respectively), fresh fruit (OR2: 0.63; OR3: 0.50), vegetable oil (OR2: 0.60; OR3: 0.52), pasta and rice (OR2: 1.06; OR3: 0.50) whereas consumption of cakes and pastries (OR2: 1.02; OR3: 2.96), sugar and confectionery (OR2: 0.96; OR3: 1.68) was associated with an increased risk. An increased risk was found for intake of saturated fat (OR2: 1.49; OR3: 1.67), simple sugars (OR2: 1.18; OR3: 1.78) and calcium (OR2: 1.84; OR3: 2.57). A decreased risk was observed with intake of fiber (OR2: 0.49; OR3: 0.59), fibre from vegetables and fruit (OR2: 0.83; OR3: 0.53) and iron (OR2: 0.70; OR3: 0.41).

Nitrosamine, nitrate and nitrite in relation to gastric cancer: a case-control study in Marseille, France.

A case-control study on gastric cancer and diet was conducted in Marseille (France). Ninety-two patients with histologically confirmed adenocarcinoma and 128 controls undergoing functional reeducation for injuries or trauma were interviewed by a trained dietician using a dietary history questionnaire on their usual diet during the year preceding the first symptoms for cases, or preceding interview for controls. Intake of nitrite, nitrate and pre-formed N-nitrosodimethylamine (NDMA) from food was estimated using a food composition table compiled ad hoc. Odds ratios (ORs) were calculated after adjustment for age, sex, occupation and calorie intake. The results indicated that high intake of NDMA was associated with increased risk for gastric cancer. The ORs for the second and third tertile of NDMA intake were: OR2 = 4.13 (95% CI = 0.93 18.27) and OR3 = 7.00 (95% CI = 1.85 to 26.46). Intake of nitrate and nitrite was not associated with increased risk of stomach cancer. Consumption of vegetables was protective in general and independent of their estimated nitrate content.

[Evaluation of ambulatory anesthesia at CHU, Brest]. / Evaluation de l'anesthésie ambulatoire au CHU de Brest.

Outpatient anaesthesia was investigated for a two-month period by means of a questionnaire filled from the preoperative anaesthesia consultation to the surgical procedure and the discharge of the patient. 868 consultations led to schedule 260 ambulatory procedures. ENT (88 patients), paediatric surgery (73 patients) and gynaecology (63 patients) were most frequently concerned. Indications of ambulatory practice could probably be enlarged provided that recovery rooms and surgical schedules were fully adapted.

Cancer and polyps of the colorectum and lifetime consumption of beer and other alcoholic beverages.

Two parallel case-control studies were conducted in the Marseilles metropolitan area of France from 1979 to 1985 on cancers and adenomatous polyps of the colorectum. All cases of cancer (n = 389) and polyps (n = 252) were incident and histologically confirmed. Controls (n = 641) matched for sex and age were selected among patients undergoing functional reeducation for injury or trauma in one of five hospital centers. Intake of alcoholic beverages was investigated by questions on daily or weekly intake of wine, beer, apéritifs, and distillates during different life periods. Questions on alcoholic beverages were integrated in a detailed diet history interview questionnaire. The risk of rectal cancer was elevated in male beer drinkers (relative risk = 1.73, 95% confidence interval 1.01-2.95) and in men and women combined (relative risk = 1.71), while beer consumption was not associated with colon cancer. Total ethanol intake and consumption of wine and distillates were not associated with the risk of cancer of the colon or rectum, nor with risk of polyps. Adjustment in the statistical analysis for energy intake and for other dietary variables (fiber from fruits and fiber from vegetables), which were found to be risk factors in the study, did not substantially change the results found for beer and other alcoholic beverages. Etiologic hypotheses related to nitrosamine content of beer are discussed in the light of growing epidemiologic evidence that beer consumption specifically increases the risk of rectal cancer.

VPX mutants of HIV-2 are infectious in established cell lines but display a severe defect in peripheral blood lymphocytes.

Nucleotide sequence comparison between HIV-1, HIV-2 and SIV has revealed the presence of an open reading frame (ORF) in the central region of the genomes of HIV-2 and SIV that has no counterpart in HIV-1. This new ORF, called vpx, is highly conserved between HIV-2ROD and SIVmac. Using anti-peptide sera to the predicted protein and site-directed mutagenesis, we show that mutations in the vpx ORF eliminate the synthesis of a 16 kd protein in HIV-2 infected cells, confirming that this protein is the product of this gene. Full-length clones of HIV-2 containing these mutations are infectious in two permanent T lymphocytic cell lines and two monocytic cell lines. In contrast, we show that loss of VPX function results in a severe defect in the productive infection of human peripheral blood lymphocytes both in the amount of reverse transcriptase activity produced and in core protein expression. These findings suggest that the VPX protein plays an important role in the in vivo life cycle of the HIV-2/SIV viruses.

The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1.

The recently described human immunodeficiency virus type 2 (HIV2) is significantly divergent in sequence from the more frequently isolated human immunodeficiency virus type 1 (HIV1). Both HIV1 and HIV2 encode a transactivator that is capable of strongly stimulating expression directed by the viral long terminal repeat (LTR). Here, we define the region of the HIV2 genome encoding the transactivator and show that the specificity of the transactivator differs from that of HIV1. By deletion analysis of the HIV2-LTR, we show that both HIV1 and HIV2 transactivators require sequences within 35 to 53 bp downstream of the start of transcription. However, in order to stimulate expression at full efficiency, the HIV2 transactivator further requires sequences unique to the HIV2-LTR between nucleotides +53 and +99. Hence, HIV2 poorly transactivates the LTR of HIV1, while two divergent isolates of HIV1 will efficiently transactivate the LTR of either HIV1 or HIV2. Nonetheless, in vivo competition between the transactivators of HIV1 and HIV2 suggests that they use a common mechanism.

Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses.

Because of the growing incidence of AIDS (acquired immune deficiency syndrome), the need for studies on animal models is urgent. Infection of chimpanzees with the retroviral agent of human AIDS, the human immunodeficiency virus (HIV), will have only limited usefulness because chimpanzees are in short supply and do not develop the disease. Among non-human primates, both type D retroviruses and lentiviruses can be responsible for immune deficiencies. The D-type retroviruses, although important pathogens in macaque monkey colonies, are not satisfactory as a model because they differ in genetic structure and pathophysiological properties from the human AIDS viruses. The simian lentivirus, previously referred to as simian T-cell lymphotropic virus type III (STLV-III), now termed simian immunodeficiency virus (SIV) is related to HIV by the antigenicity of its proteins and in its main biological properties, such as cytopathic effect and tropism for CD4-bearing cells. Most importantly, SIV induces a disease with remarkable similarity to human AIDS in the common rhesus macaques, which therefore constitute the best animal model currently available. Natural or experimental infection of other monkeys such as African green monkeys or sooty mangabeys has not yet been associated with disease. Molecular approaches of the SIV system will be needed for biological studies and development of vaccines that could be tested in animals. We have cloned and sequenced the complete genome of SIV isolated from a naturally infected macaque that died of AIDS. This SIVMAC appears genetically close to the agent of AIDS in West Africa, HIV-2, but the divergence of the sequences of SIV and HIV-2 is greater than that previously observed between HIV-1 isolates.

Genome organization and transactivation of the human immunodeficiency virus type 2.

Analysis of the nucleotide sequence of the human retrovirus associated with AIDS in West Africa, HIV-2, shows that it is evolutionarily distant from the previously characterized HIV-1. We suggest that these viruses existed long before the current AIDS epidemics. Their biological properties are conserved in spite of limited sequence homology; this may help the determination of the structure-function relationships of the different viral elements.

Molecular cloning and polymorphism of the human immune deficiency virus type 2.

We recently reported the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of the AIDS epidemic now spreading in Central and East Africa, as well as the USA and Europe (see ref. 3 for review) both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. But preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera. We now report the molecular cloning of the complete 9.5-kilobase (kb) genome of HIV-2, the observation of restriction site polymorphism between different isolates, and a preliminary analysis of the relationship of HIV-2 with other human and simian retroviruses.

[Mortality after regular implantations of total hip prostheses]. / Mortalité après implantations réglées de prothèses totales de hanche.

Operative and post operative (two months) mortality among 1280 patients undergoing total hip replacement is studied. Mortality rate was 1%. The main cause is pulmonary embolism, then mental deterioration and anaesthesia. Use of methylmethacrylate did not cause death. Rheumatoid arthritis could increase the risk.

[Normovolemic hemodilution without previous blood collection]. / Hémodilution normovolémique sans prélèvement sanguin préalable.

Iso-volaemie hemodilution without preoperative blood letting was produced inpatients undergoing orthopedic surgery. Bleeding was compensated by a modified fluid gelatin-electrolyte solution until a predetermined volume was reached. Further blood-loss was compensated by blood transfusion. Clinical condition, hematocrit, coagulation and renal function were observed in the per- and post-operative period.