[Psychosocial distress and communication about cancer in ill partners and their spouses]. / Détresse psychosociale et communication à propos du cancer chez le partenaire malade et son conjoint.

INTRODUCTION: Each cancer can have a psychological impact not only on the patient himself/herself, but also on his/her spouse. OBJECTIVE: Our study concerned 30 couples encompassing a member treated for a cancer, non related to gender. It was aimed at determining the links between the levels of psychosocial distress measured in both members of each couple, patients' sociodemographic and clinical characteristics, as well as communication skills about cancer in both members of the couples. METHODS: Psychosocial distress and communication about cancer were measured by the general health questionnaire (GHQ-28) and the openness to discuss cancer in the nuclear family (ODCF), with an additional version adapted for the spouse on the occasion of this study. RESULTS: A positive correlation was found between the respective scores of the two members of the couples, for the GHQ-28 (r=0.53; p=0.005) as well as for the ODCF (r=0.44; p=0.024). GHQ-28 scores were not associated with the sociodemographic characteristics of the patients, nor with the stage of cancer, the number of months elapsed since the diagnosis of cancer, or the ODCF personal or spouse's score. On the other hand, when the communication within each couple was classified into concordant (insufficient or, on the contrary, open for both members) or discordant (insufficient for one of the two members and open for the other), and after controlling for gender, higher levels of psychosocial distress were found in patients (p=0.038) as well in spouses (p=0.052) belonging to discordant compared with concordant couples. CONCLUSION: These results suggest an effect of contamination or a mutual reinforcement of the distress of each member of such couples, as well as the presence of relatively similar styles of communication in the two partners of each couple. They also underline the possible adaptive function of a restricted style of communication about cancer, if such a restriction is shared by both the members of the couple, and incites particular attention to be paid to couples where one of the partners, but not the other, adopt an open style of communication about cancer.

[Insulinoma presenting as pseudo-drug-resistant focal epilepsy]. / Un insulinome se présentant comme une épilepsie focale pharmacorésistante.

INTRODUCTION: We describe a case of insulinoma presenting as a refractory frontal lobe epilepsy in a 44-year-old man with a history of severe head trauma. CASE REPORT: Despite escalating treatment, his seizure frequency worsened during the previous year. He also developed psychomotor slowing and sweating occurring early in the morning. He gained weight. Insulinoma was diagnosed based on the presence of episodes of hypoglycemia, abnormal insulin/blood glucose ratio and a tumor in the pancreas (echo-ultrasound). After partial pancreatectomy, the patient became seizure free and anti-epileptic drugs were progressively stopped, with a follow-up of five years. CONCLUSION: Insulinoma should be considered in patients with no reason for having drug-resistant epilepsy, especially when seizures occur early in the morning or when episodes of neuropsychiatric symptoms with sweating are present.

[Influence of the communication about one parent's cancer on children's suffering]. / Influence de la communication à propos du cancer d'un parent sur la souffrance des enfants.

INTRODUCTION: Factors contributing to children's distress when a parent is affected with a cancer are still insufficiently known. This study aimed at searching for associations between psychosocial distress in children living with a parent suffering from cancer, the severity of parental cancer, the levels of psychosocial distress in both parents and the openness to discuss cancer in the family. METHODS: Thirty families encompassing a parent treated for cancer and 54 children aged four to 16 were examined. Each parent's psychosocial distress was assessed by the General Health Questionnaire (GHQ-28) and the distress of the children living within the family by the Child Behavior Check List (CBCL) filled out by both parents. Each parent's communication ability about cancer was assessed by the Openness to Discuss Cancer in the nuclear Family questionnaire (ODCF). RESULTS: No association was found between children's distress and objective cancer characteristics. Higher externalized disorders scores at CBCL (aggression) were found when the ill parent was the mother (P=0.018). After controlling for cancer parent's gender, CBCL total score and internalized disorders (anxiety, depression) score were higher in families characterized by an "open" style of communication, defined on the parental couple as a whole (respectively p=0.007 and 0.024), such an effect being present only when the ill parent was the mother (interaction effect: p<0.001). CONCLUSION: These results underline the importance of family characteristics for understanding the suffering observed in children living with a parent affected with a cancer in comparison with objective cancer characteristics.

Prostate-specific antigen doubling time before onset of chemotherapy as a predictor of survival for hormone-refractory prostate cancer patients.

BACKGROUND: We evaluated the possible use of prostate-specific antigen doubling time (PSA-DT) before chemotherapy initiation as a surrogate marker of survival in hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Data from 250 consecutive metastatic HRPC patients treated with chemotherapy between February 2000 and November 2006 were retrospectively analysed. At least three PSA assays were required within 3 months before chemotherapy. PSA-DT was calculated as ln 2 divided by the slope of the log PSA line, and the difference between two log PSA levels was divided by the time interval. The primary endpoint was overall survival (OS). Survival rates according to PSA-DT were stratified on chemotherapy regimen. Multivariate Cox regression analysis was performed to isolate the impact of PSA-DT on OS, controlling for associate prognostic covariates. RESULTS: Patients received docetaxel- (82%) or mitoxantrone-based chemotherapy. The median PSA-DT was 45 days (range 4.7-1108 days). There were 174 deaths (70%). The median survival was 16.5 months (95% confidence interval [CI] = 12.5-20.5) and 26.4 months (95% CI = 20.3-32.4) for patients with a PSA-DT < 45 and > or =45 days, respectively. In the multivariate setting, the adjusted hazard ratio (HR) was 1.39 (95% CI = 1.03-1.89; P = 0.04), stratified by chemotherapy regimen. CONCLUSION: A short PSA-DT before onset of chemotherapy in HRPC patients was associated with an increased risk of death. This could be useful as a stratification parameter in trials with new drugs in a metastatic setting.

A dendritic cell-based vaccine for treating HIV infection: background and preliminary results.

Antibody response against human immunodeficiency virus-1 (HIV) is ineffective and cellular immune response is not strong enough to achieve the complete suppression or at least a strong control of viral replication in HIV- infected patients. In 2001, we showed in vitro that dendritic cells (DCs) of HIV-infected patients loaded with autologous HIV chemically inactivated by aldrithiol-2 were capable of raising an HIV-specific cellular immune response powerful enough to allow the destruction of autologous HIV- infected CD4 T cells. In 2003, we showed that simian immunodeficiency virus (SIV)-infected macaques vaccinated with inactivated SIV-loaded autologous DCs raised a strong SIV-specific cellular response. Ten months after vaccination, plasma viral load of 7 out of the 10 vaccinated monkeys remained 1000-fold lower than initially. In December 2004, we published results observed in 18 untreated HIV-infected patients vaccinated with autologous monocyte-derived DCs loaded with autologous inactivated HIV. A year following vaccination, 8 patients had a plasma viral load decrease >90%; among them, 4 had viral load <1000 copies mL(-1). Moreover, by one year, the viral load decline of the 18 patients was significantly correlated with their percentage of HIV-1-gag-specific CD8(+) T cells expressing perforin and that of HIV-1-specific CD4(+) T(H)1 cells. This is the first demonstration of the capacity of a therapeutic vaccine to induce an effective HIV-specific T cell response associated with sustained viral suppression in untreated viremic patients. The manipulation of antigen presenting cells to elicit virus-specific cellular responses is a promising tool to control persistant viral infections.

[Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry]. / Stratégies thérapeutiques dans les adénomes somatotropes avec extension extrasellaire. Place du traitement médical. Etude consensus du Répetoire français de l'Acromégalie.

UNLABELLED: From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.

Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy.

This retrospective study compares high-dose therapy (HDT) with autologous stem cell transplantation and combined-modality treatment (CT) as a first-line therapy for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at diagnosis, and an incomplete response after the first-line chemotherapy. Data on 42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81 and H90) was analyzed. Both groups were comparable except for pulmonary disease in excess in the grafted group (P = 0.01). Among GP, 95% were in complete response at the end of first-line treatment and 77% among CTP. Median follow-up was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181 months) for CTP. The 5-year freedom from progression (FFP) and event-free survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81% vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were obtained for the groups with a response > or =50% after initial chemotherapy: 91% vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003; 72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows a better control of the disease with HDT.

In vitro human immunodeficiency virus eradication by autologous CD8(+) T cells expanded with inactivated-virus-pulsed dendritic cells.

Despite significant immune recovery with potent highly active antiretroviral therapy (HAART), eradication of human immunodeficiency virus (HIV) from the bodies of infected individuals represents a challenge. We hypothesized that an inadequate or inappropriate signal in virus-specific antigen presentation might contribute to the persistent failure to mount efficient anti-HIV immunity in most HIV-infected individuals. Here, we conducted an in vitro study with untreated (n = 10) and HAART-treated (n = 20) HIV type 1 (HIV-1) patients which showed that pulsing of monocyte-derived dendritic cells (DC) with aldrithiol-2-inactivated autologous virus resulted in the expansion of virus-specific CD8(+) T cells which were capable of killing HIV-1-infected cells and eradicating the virus from cultured patient peripheral blood mononuclear cells independently of the disease stages and HAART response statuses of the patients. This in vitro anti-HIV effect was further enhanced by the HIV protease inhibitor indinavir (at a nonantiviral concentration), which has been shown previously to be able to up-regulate directly patient T-cell proliferation following immune stimulation. However, following a 2-day treatment with culture supernatant derived from immune-activated T cells (which mimics an in vivo environment of HIV-disseminated and immune-activated lymphoid tissues), DC lost their capacity to present de novo inactivated-virus-derived antigens. These findings provide important information for understanding the establishment of chronic HIV infection and indicate a perspective for clinical use of DC-based therapeutic vaccines against HIV.

Enhanced dendritic cell-driven proliferation and anti-HIV activity of CD8(+) T cells by a new phenothiazine derivative, aminoperazine.

T cell anergy, apoptosis, and chronic activation of T lymphocytes are prevailing features of HIV infection. The inability to develop an efficient natural antiviral activity in infected patients might be the consequence of a failure of the Ag presentation by dendritic cells (DCs) in chronically activated lymphoid tissues. We have identified a new phenothiazine derivative aminoperazine (APR; 2-amino-10-[3'-(1-methyl-4-piperazinyl)propyl]phenothiazine, C(20)H(26)N(4)S; m.w. 354.51) able to increase (effective dose from 0.1 to 100 nM) the Ag-specific DC-driven proliferation and differentiation of in vitro HIV-infected and uninfected normal donor T cells and of T cells from HIV-1-infected patients. The immunomodulatory effect of APR-sensitized DCs were ascribed to soluble factors derived from DCs. APR was also capable of increasing HIV gag-p24-specific proliferation and anti-HIV cytotoxic activity of patients' CD8(+) T cells against autologous B-lymphoblastoid cell lines expressing a HIV gag gene, resulting in the suppression of both proviral DNA and supernatant viral RNA in the HIV-1-infected patients' T cell culture. This new phenothiazine derivative (APR) might be used for boosting the immune response of vaccinated individuals and for restoring the immunity of immunocompromised patients.

Feasibility and preliminary results of intensive chemotherapy and extensive irradiation in selected patients with limited small-cell lung carcinoma--results of three consecutive phase II programs.

We report the results of three consecutive programs combining initial intensive chemotherapy and radiotherapy in the treatment of patients with limited small-cell lung cancer (SCLC). The objective was to test the feasibility and the effect of high-dose chemotherapy and three thoracic irradiation programs on survival and patterns of relapse. Forty-two patients with limited SCLC were enrolled. All patients received high-dose chemotherapy (vindesine, etoposide, doxorubicin, cisplatin and cyclophosphamide or ifosfamide). In the SC 84 program, chest and brain radiotherapy was delivered during each course of chemotherapy, with a complementary irradiation after chemotherapy. In the SC 86 and SC 92 programs, patients received chemotherapy followed by thoracic irradiation and prophylactic brain and spinal axis radiotherapy. At the end of treatment, 40 patients (95%) were in complete response. During chemotherapy, high levels of toxicity were noted. All patients had grade IV hematological toxicities. The extra-hematological toxicities were digestive (grade III: 21%; grade IV: 7%) and hepatic (grades III and IV: 14%). During irradiation, patients presented digestive, pulmonary and hematological toxicities. Five patients developed late toxicities and a second malignancy was observed in 4 patients. The 2- and 5-year survival rates for all patients were 51% and 27%, respectively. Despite the marked toxicity of the initial intensive chemotherapy, the treatments are tolerable and effective in the control of extra-thoracic micrometastases, whereas they are less effective for thoracic primary tumor.

HIV protease inhibitors restore impaired T-cell proliferative response in vivo and in vitro: a viral-suppression-independent mechanism.

In 99 adults infected with human immunodeficiency virus type 1 (HIV-1) who received highly active antiretroviral therapy (HAART) (including 2 nucleoside analogues and 1 or 2 protease inhibitors) for 1 year, CD4(+) and CD8(+) T cells (including memory and naive subsets) increased similarly among patients with sustained plasma viral load decrease, transient decrease, or no decrease. A linear correlation was observed between the decrease in serum beta(2)-microglobulin concentration (an independent surrogate marker of HIV disease) and the increase in peripheral blood T-cells (CD4(+) and CD8(+)) counts. In vitro, HIV protease inhibitors indinavir and saquinavir (but not nucleoside analogues) enhanced the survival of patients' peripheral blood T cells at doses that are at least 30-fold lower than those required for achieving 90% viral inhibition in the same cultures. This enhanced T-cell survival (which is similar for CD4 and CD8 cells) was associated with a restoration of T-cell proliferative response to immune stimuli. However, neither TCR/CD3-ligation- nor Fas-ligation-triggered apoptosis was affected by either of the 2 protease inhibitors. A reduction in apoptosis observed after prolonged culture of patient T cells in the presence of the protease inhibitors could result from restored T-cell proliferation. These findings explain the discrepancies between virologic and immunologic responses that are increasingly reported in patients receiving HAART, and may provide insights into the pathogenesis of HIV infection.

Quantitative analysis of the antiviral activity of CD8(+) T cells from human immunodeficiency virus-positive asymptomatic patients with different rates of CD4(+) T-cell decrease.

We have measured in 22 asymptomatic human immunodeficiency virus type 1-infected patients (10 rapid progressors and 12 slow progressors) the proviral load of CD4(+) T cells homogeneously superinfected by the same dose of a non-syncytium-inducing virus in the presence or in the absence of autologous CD8(+) T cells. We demonstrated that the antiviral activity of CD8(+) T cells was highly predictive of the rate of peripheral CD4(+) T-cell decline.

Nocardia thyroiditis: unusual location of infection.

Nocardia asteroides complex is an important opportunistic agent in immunocompromised hosts. Usually, primary pulmonary infection occurs and is followed by dissemination of the pathogen to the central nervous system and soft tissues. As described in the literature, almost every organ can be infected, but to our knowledge, Nocardia has been described as a pathogen responsible for thyroid abscess in only one report, which was published in 1993. The present report is the second case report of Nocardia thyroiditis. The patient was under immunosuppressor treatment following a combined liver-kidney transplant and presented with a preexisting nodular goiter which was probably a predisposing factor to the start and development of the thyroid infection.

New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.

The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression. The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11. These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development.

Distinctive effects of CCR5, CCR2, and SDF1 genetic polymorphisms in AIDS progression.

The Genetics of Resistance to Infection by HIV-1 (GRIV) cohort represents 200 nonprogressor/slow-progressor (Slowprog) and 90 fast-progressor (Fastprog) HIV-1-infected patients. Using this unique assembly, we performed genetic studies on three recently discovered polymorphisms of CCR5, CCR2, and SDF1, which have been shown to slow the rate of disease progression. The increased prevalence of mutant alleles among Slowprogs from the GRIV cohort was significant for CCR5 (p < .0001) but not for CCR2 (p = .09) or SDF1 (p = . 12), emphasizing the predominant role of CCR5 as the major HIV-1 coreceptor. However, the prevalence of the CCR2 mutant allele (64I) was significantly increased among Slowprogs homozygous for wild-type CCR5 compared with Fastprogs (p = .04). The prevalence of double mutants SDF1-3'A/3'A genotypes was also increased among Slowprogs homozygous for wild-type CCR5 compared with Fastprogs (p = .05). The effects of the CCR2 and SDF1 mutations are overshadowed by the protective effects of the CCR5 deletion. Predictive biologic markers such as CD4 cell counts or viral load in the Slowprog population did not show significant differences between Slowprog groups with wild-type or mutant alleles for the three genes. Thus, our data suggest that the effects of these genes are exerted earlier in infection and no longer evident in the Slowprog of the GRIV cohort whose average duration of HIV infection is 12 years. We conclude that these genes, whose products serve as viral coreceptors or their ligands, may play a role early in infection and delay the onset of disease. However, among Slowprogs, whose duration of infection is >8 years, they are no longer influential for maintenance of their longterm nonprogression status. Other genetic determinants may be responsible for late protective effects.