Astragalus-containing Traditional Chinese Medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: a systemic review and meta-analysis.

OBJECTIVE: Traditional Chinese Medicine (tcm) is used in China as part of the treatment for non-small-cell lung cancer (nsclc) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced nsclc. METHODS: We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, embase, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (hr) or relative risk (rr), with corresponding 95% confidence intervals (cis). RESULTS: Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based tcm to chemotherapy was associated with significantly increased overall survival (hr: 0.61; 95% ci: 0.42 to 0.89; p = 0.011); 1-year (rr: 0.73; 95% ci: 0.65 to 0.82; p < 0.001), 2-year (rr: 0.3344; 95% ci: 0.237 to 0.4773; p < 0.001), and 3-year survival rates (rr: 0.30; 95% ci: 0.17 to 0.53; p < 0.001); performance status (rr: 0.43; 95% ci: 0.34 to 0.55; p < 0.001); and tumour overall response rate (rr: 0.7982; 95% ci: 0.715 to 0.89; p < 0.001). Subgroup analyses indicated that Astragalus herbal formulae given based on syndrome differentiation were more effective than Astragalus-based oral and injection patent medicines. Side effects-including anemia, neutropenia, thrombocytopenia, fatigue, poor appetite, nausea, and vomiting-were significantly more frequent with platinum-based chemotherapy alone than when platinum-based chemotherapy was combined with Astragalus-based tcm. CONCLUSIONS: Astragalus-based Chinese botanical therapy, especially when based on syndrome differentiation, is associated with increased efficacy of platinum-based chemotherapy and decreased platinum-derived toxicities for patients with advanced nsclc.

Genetic evidence reveals temporal change in hybridization patterns in a wild baboon population.

The process and consequences of hybridization are of interest to evolutionary biologists because of the importance of hybridization in understanding reproductive isolation, speciation, and the influence of introgression on population genetic structure. Recent studies of hybridization have been enhanced by the advent of sensitive, genetic marker-based techniques for inferring the degree of admixture occurring within individuals. Here we present a genetic marker-based analysis of hybridization in a large-bodied, long-lived mammal over multiple generations. We analysed patterns of hybridization between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in a well-studied natural population in Amboseli National Park, Kenya, using genetic samples from 450 individuals born over the last 36 years. We assigned genetic hybrid scores based on genotypes at 14 microsatellite loci using the clustering algorithm implemented in STRUCTURE 2.0, and assessed the robustness of these scores by comparison to pedigree information and through simulation. The genetic hybrid scores showed generally good agreement with previous morphological assessments of hybridity, but suggest that genetic methods may be more sensitive for identification of low levels of hybridity. The results of our analysis indicate that the proportion of hybrids in the Amboseli population has grown over time, but that the average proportion of anubis ancestry within hybrids is gradually decreasing. We argue that these patterns are probably a result of both selective and nonselective processes, including differences in the timing of life-history events for hybrid males relative to yellow baboon males, and stochasticity in long-distance dispersal from the source anubis population into Amboseli.

Lung cancer in HIV infected patients: facts, questions and challenges.

AIDS related mortality has fallen sharply in industrialised countries since 1996 following the introduction of highly active antiretroviral therapy. This has been accompanied by an increase in the proportion of deaths attributable to non-AIDS defining solid tumours, especially lung cancer. The risk of developing lung cancer seems to be higher in HIV infected subjects than in the general population of the same age, partly because the former tend more frequently to be smokers and, especially, intravenous drug users. The carcinogenic role of the antiretroviral nucleoside drugs and their interaction with smoking needs to be examined. Interestingly, there is no clear relationship between the degree of immunosuppression and the risk of lung cancer, so the reason for the increased risk is unknown. The mean age of HIV infected patients at the time of lung cancer diagnosis is 45 years and most are symptomatic. Lung cancer is diagnosed when locally advanced or metastatic (stage III-IV) in 75-90% of cases, similar to patients with unknown HIV status. Adenocarcinoma is the most frequent histological type. The prognosis is worse in HIV infected patients than in the general lung cancer population. Efficacy and toxicity data for chemotherapy and radiation therapy are few and imprecise. Surgery remains the treatment of choice for localised disease in patients with adequate pulmonary function and general good health, regardless of immune status. Prospective clinical trials are needed to define the optimal detection and treatment strategies for lung cancer in HIV infected patients.

Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: results of two Phase II, multicenter trials.

The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.

A phase II multicenter study of combined topotecan and gemcitabine as first line chemotherapy for advanced non-small cell lung cancer.

UNLABELLED: This trial was designed to determine the 1-year survival rate, efficacy, and safety, produced by topotecan and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (ANSCLC). Fifty-three patients were enrolled; 51 received treatment. Topotecan 1 mg/m(2), days 1-5 and gemcitabine 1 g/m(2) days 1 and 15 were administered IV, each drug over 30 min; cycles consisted of 28 days. Treatment continued until progressive disease or intolerable toxicity. Nineteen patients (36%) had Eastern Cooperative Oncology Group criteria performance status (ECOG PS) = 0, 34 (64%) PS = 1. Median age was 64 years; 37 patients (70%) were male. HISTOLOGY: adenocarcinoma (42%), squamous cell carcinoma (28%), large cell (19%), and unclassified (11%). Among 47 evaluable patients, eight (17%) had partial response, 11 (23%) had stable disease. One-year survival was 39% and median survival was 7.6 months (range, < 1-19.6). Grade 3 and 4 toxicities included neutropenia (53%), anemia (18%), thrombocytopenia (12%), asthenia (8%), and gastrointestinal disorders (8%); three patients (6%) experienced neutropenic fever. There were no treatment-related deaths. The combination topotecan/gemcitabine produced a 1-year survival similar to previous platinum-based regimens, when used as first line chemotherapy for ANSCLC. The toxicity profile was acceptable.

Open trial of nefazodone for combat veterans with posttraumatic stress disorder.

Fourteen combat veterans completed a 9-week open trial of nefazodone for treatment of posttraumatic stress disorder (PTSD). Overall PTSD symptoms as measured by the Clinician-Administered PTSD Scale (CAPS) showed a modest but statistically significant decrease with nefazodone treatment. Decreases in CAPS reexperiencing and avoidance, but not hyperarousal symptoms, approached statistical significance. Anxiety decreased significantly, and there were trends toward decreased depression and anger on structured assessments. This study adds to the clinical evidence that nefazodone may be helpful for the management of PTSD symptoms.

Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma.

We established short-term cell lines for 108/170 (64%) patients with metastatic melanoma. Tumor cell numbers were expanded to 10(8), then cells were irradiated, aliquoted, and cryopreserved for clinical use. Vaccines have been used to treat 69 patients with clinical follow up for 33 who had measurable metastatic disease at the time vaccine therapy was initiated (METS), and 33 who had no evidence of disease (NED) at the time of vaccine therapy following surgical resection of metastases. The protocol called for a baseline test of delayed tumor hypersensitivity (DTH), three weekly injections, a repeat of the DTH test, then monthly injections for an additional 5 months. Objective tumor responses were noted in 3/26 (12%) patients who received a minimum of three vaccinations, one complete, and two partial, with survivals of 36, 46+, and 78+ months. Only 6/64 (9.4%) had a positive DTH (>10 mm) at baseline, including three METS, all of whom progressed within 4 months and died within a year, and three who are still NED after more than 5 years. Conversion of DTH from negative to positive was documented in 18/44 (41%) patients who were tested at week 0 and 4. At a median follow up of greater than 5 years, the median overall survival (OS) was 40 months for "NED" with a 5-year survival rate of 39%, and 8.6 months with a 5-year survival rate of 10% for "METS" The 18 patients who had conversion of their DTH had a median event-free survival (EFS) of 15.8 months and 5-year EFS of 32% compared to 4.2 months and 9% for the 26 non-converters (P=0.012, two-tailed, log-rank test). Among patients who were NED when treatment started, the 12 patients whose DTH converted had a median overall survival of 61.4 months with 5-year survival of 63% compared to 9.7 months and 0% for the 13 non-converters (P=0.0026). This treatment approach is feasible, produces minimal toxicity, and is associated with long-term survival in a significant subset of patients.

Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.

BACKGROUND: We established short-term cultures of autologous tumors from patients with renal carcinoma for use as active specific immunotherapy (i.e., autologous vaccine). METHODS: Between 9/91 and 9/99 the cell biology laboratory of the Hoag Cancer Center received 69 kidney tumor samples that had been surgically excised, including 43 primary tumors and 26 metastatic lesions. Efforts were made to establish short-term tumor cell cultures to use as autologous tumor cell vaccines. Prior to treatment, patients underwent a baseline skin test for delayed tumor hypersensitivity (DTH) and then received s.c. injections of 10 million irradiated tumor cells that were given with various adjuvants weekly x3 and then monthly x5. RESULTS: Cell lines were established for 55/69 patients (80%) including 36/43 (84%) from primary tumors and 19/26 (73%) from distant metastases. Vaccines were prepared for 41 patients; 27 were treated. At the time of this analysis, follow up data was available for 26 patients with a median follow up > 5 years. Treatment was well-tolerated. Of 10 patients who had no evident disease at the time of treatment, nine were alive 1-8 years later; 5/8 had conversion of their DTH test from negative to positive. For 16 patients with measurable metastatic disease at the time of treatment, there were no objective tumor responses; their median survival was 5.0 months. Among these 16 patients, only 1/8 DTH tests converted, but three had a positive baseline DTH test; one was previously treated with interleukin-2 and tumor infiltrating lymphocytes and two others were previously treated with autolymphocyte therapy. CONCLUSIONS: Vaccine therapy with short-term cultures of autologous tumor cells is feasible, well-tolerated and associated with conversion of DTH and long-term survival in patients who are free of disease at the time treatment is initiated. However, significant anti-tumor responses were not seen in patients with measurable disease at the time vaccine treatment was initiated.

The use of self-psychological concepts in a Veterans Affairs PTSD clinic.

The authors describe the advantages of self-psychological concepts in the treatment of combat veterans with posttraumatic stress disorder (PTSD). Classical psychoanalytic views of PTSD opened the door to understanding PTSD as a type of "narcissistic neurosis." Although many psychological and psychoanalytically oriented treaters of PTDS acknowledge that the entire personality needs rehabilitation and, thus, a comprehensive approach to the PTSD patient is indicated, most stay close to the primacy of pathological memory. Self psychology, with its specific view on damage and repair of the self and the key importance of the selfobject transference in that process, provides a focus wherein damage to the self comes first and alterations in other psychological systems take on an important but secondary emphasis. The authors outline the central elements of PTSD in combat veterans and review the contributions of psychoanalysis to their treatment. Core concepts from self psychology are detailed, and three vignettes of veterans treated in an outpatient PTSD clinic are offered to illustrate the specific mirroring, idealizing, and twinship selfobject transferences they bring to the treatment situation. Finally, a discussion of each vignette highlights how self psychology's focus on strengthening the damaged self has aided in patients' improvement.

Lupron-induced mania.

BACKGROUND: Gonadotropins and sex hormones are intimately related to the stability of affective states. Patients with affective disorders may demonstrate abnormal levels of sex hormones and gonadotropins. It is therefore possible that affective disorder patients may experience mood dysregulation by synthetic sex hormones and gonadotropins like lupron. METHODS: A case report of a young woman with a history of endometriosis and a past history of irritability and depression is described. Treatment of the endometriosis with lupron induced a manic episode. RESULTS: The lupron-induced mania was successfully treated with a mood-stabilizing agent, lithium carbonate. CONCLUSIONS: Patients with a history of affective disorder may develop manic episodes when treated with Lupron. Mood-stabilizing agents are helpful in ameliorating this unwanted effect.

All the king's horses and all the king's men. Three forms of curative audience in the recovery from psychosis.

This essay discusses an overlooked ingredient in the psychotherapy of psychosis which is termed the "curative audience." Central to the equation of psychological selfhood is the evocation of a sense of self by experiences that the patient has with objects in the environment. This essay calls attention to an essential function of this environment, namely, that it provides an audience that makes it possible for these "selfobject" transferences, transference interpretations or new, helpful relational experiences to become significant. In essence, it is argued that a "private experience" without an internal or external audience is not therapeutic in the reassembly of self, especially when the power and intensity to overcome psychotic disintegration is required. The idea that the psychotic patient recompensates not only with the help of a therapist but under the auspices of a third entity, has not been previously discussed. Interestingly, all the schools of psychoanalysis have touched on the role of audience in the healing of patients with both neurosis and psychosis, yet this thread has not been followed into its binding together of subjectivity. Three forms of curative audience can be identified corresponding to the beginning, middle, and end phases of treatment. The role of audience in the reassembly of the self is taking its first form in the initial contact or initial relationship with the other and over time develops into the second form, the therapeutic alliance. In the third form of the curative audience, the establishment of an external selfobject milieu that performs the functions of the curative audience is seen as essential to continued cohesion in the recovery from psychosis. Performative statements exert self-cohering effects and can be seen to have their source in the curative audience. Two clinical vignettes were presented to illustrate these ideas.

Gender differences in body satisfaction.

Although men and women show similar rates of obesity, women more frequently engage in weight loss efforts, with potentially adverse health consequences. We surveyed 320 college-aged men and women to examine gender differences in the determinants of body dissatisfaction and the degree of importance assigned to bodyweight and shape. Results indicated that, for both genders, satisfaction with bodyweight and shape decreased as body mass index (BMI) increased. Women, however, showed significantly greater body and weight dissatisfaction than men at most weight categories. Only the underweight (BMI < 20) women and men were similarly satisfied with their bodyweight and shape. As BMI increased, however, women became disproportionately more dissatisfied: both normal-weight and overweight women expressed greater dissatisfaction than comparable men. College-aged women also attributed progressively more importance to both weight and shape as BMI increased, unlike college-aged men, who considered body weight equally important to (or slightly less important than) self-esteem as BMI increased. We discuss implications for the self-esteem of obese women and men.

[Dens in dente: apicoectomy and retrograde obturation]. / Dens in dente: apectomie et obturation à rétro.

Dens in dente is a developmental anomaly, which, in some advanced cases, requires a combination of conventional and surgical endodontic treatment. The purpose of this article is to suggest how to treat a Type 3 (Oehlers classification) dens in dente.

Containers, mental space and psychodynamics.

The concept of the container has a place within cognitive science as well as within psychodynamic theories. Cognitive semantics has shown that many metaphors giving meaning to daily life-events use the container as a basic reference point. Psychoanalytic theory, most notably, Freud's psychosexual developmental model, illustrates how the container of the body results in meaning. Object relations theory in psychoanalysis has shown how patients with borderline personality disorder behave according to the dynamics of container and containment. Both the cognitive and the psychodynamic conceptions of containers are clinically relevant. The fundamental notion of the container leads to an exploration of 'container dynamics' both in cognitive semantics and in psychodynamic work. A model of the cusp may be of help in the description of the dynamics at the border of the container. Furthermore, the descriptions of the patient's communication of emotion and thoughts may involve three interacting dimensions: an effective-perceptual dimension, a phantasy dimension and a socio-interactive dimension. The interaction between these dimensions has implications for dealing with container dynamics and the process of containment.