Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer.

UNLABELLED: This is a dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide, in chemo naïve patients with advanced non-small cell lung cancer. The purpose of the study was to determine the optimal dosage and the maximal tolerated dose (MTD) of a specified schedule of gemcitabine and ifosfamide. Patients received gemcitabine 1250 mg/m2 and ifosfamide between 1.6 and 2.2 g/m2, intravenously, on days 1 and 8, repeated every 3 weeks for a maximum of four cycles. RESULTS: Sixteen patients entered the study. Three patients were entered at the first dose level of ifosfamide (1.6 g/m2) and none experienced any dose limiting (DLT) toxicity. In dose level 2 (1.8 g/m2), two patients had grade IV haematological toxicities, but they reached 21 days without any other dose limiting toxicity (DLT). Three further patients entered at this level but they were withdrawn due to disease progression. The sixth patient entered without any DLT. Three patients entered dose level 3 (2.0 g/m2), without any grade IV toxicity. The first patient entered into dose level 4 (2.2 g/m2), had progressive disease within 21 days and was withdrawn and another three were entered and had no DLT during the first 21 days. Four (33%) of the patients had stable disease and 67% had progressive disease. CONCLUSION: The MTD of the ifosfamide gemcitabine combination was not reached in the present study, as no DLT was observed. This combination at the dose levels of this protocol has little or no activity in patients with advanced NSCLC.

Phase I dose-escalating study of raltitrexed ('Tomudex') and cisplatin in metastatic non-small cell lung cancer.

BACKGROUND: The aim of this Phase I, dose-escalation study was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of a raltitrexed ('Tomudex') and cisplatin combination in patients with previously untreated, metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received raltitrexed (15-min intravenous infusion), followed by cisplatin (1-h intravenous infusion), every 3 weeks at escalating dose levels. RESULTS: In total, 21 patients entered the study. No DLT was observed up to dose level 4 (raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2)), or in the first 3 patients who received dose level 5 (raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2)). However, 1 patient, entered at dose level 6 (raltitrexed 4.0 mg/m(2) plus cisplatin 80 mg/m(2)) experienced severe toxicity (including grade 3 diarrhea), and no further patients were recruited at this level. Of 4 additional patients who received raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), 3 also experienced DLTs. The most common adverse events included nausea/vomiting, asthenia, diarrhea, and hematologic toxicities. Of 19 patients evaluated for response, 3 achieved a partial response, 13 had stable disease, and 3 progressed. CONCLUSIONS: The MTD is raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), and the RD for future studies is raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2); DLTs were diarrhea and asthenia. The combination of raltitrexed and cisplatin shows clinical activity in patients with metastatic NSCLC.

Team collaboration: a case study of an early intervention team.

The study described in this article sought to examine the workings of an interdisciplinary team as a research entity and as a service provider. There were two levels of analysis in the study: the process of collaborating on the research and the results of the research observation of an interdisciplinary team in a clinical setting. An interdisciplinary research team studied the interaction of a single clinical team over a 6-month period working with one child in a hospital-based early intervention program. The data were collected through intensive interviews, direct observations of the family and team members, and selected videotaping of team meetings. Qualitative data analysis methods were used, and five themes emerged: who takes the lead, the classroom as a way station, we like our freedom but..., who is giving and who is taking advice, and communication comes in few forms.

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study.

BACKGROUND: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. PATIENTS AND METHODS: Patients with chemo-naïve SCLC were randomized to standard-dose CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks, x4, with filgrastim 5 microg/kg/day days 4-13) to assess the impact on survival (n = 240 patients). Patients were also randomized to prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This manuscript focuses on the antibiotics question. RESULTS: The incidence of FL during the first cycle was 25% of patients in the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an overall incidence through all cycles of 43% vs. 24% respectively (P = 0.007; 1-sided). There were less Gram-positive (12 vs. 4), Gram-negative (20 vs. 5) and clinically documented (38 vs. 15) infections in the antibiotics arm. The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17 patients, P = 0.013: 1-sided). However, the overall number of days of hospitalization was not reduced (P = 0.05; 1-sided). The number of infectious deaths was nil in the antibiotics vs. five (6%) in the placebo arm (P = 0.022; 2-sided). CONCLUSIONS: Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered.

Adolescents' perceptions of aloneness and loneliness.

It is theorized that we are born with the need both to be alone and to be connected with others. Aloneness, like attachment, is seen as necessary for human growth, with loneliness being the negative extreme. Yet, can feelings of loneliness be distinguished from the need to be alone? To answer this question, the present paper reviews theories and research on loneliness and aloneness. In addition, the perceptions of adolescents are presented. They were found to be able to distinguish between the two states. Loneliness, as anticipated, was viewed negatively, being coupled with sadness and hopelessness. Aloneness was viewed as a neutral state. It is recommended that future research explore the positive dimensions of aloneness, including when adolescents choose to be alone, what they do while alone, and how they feel after being alone.

Neonatal temperament, maternal interaction, and the need for "alonetime".

In one of a set of studies exploring the need for time alone throughout development, infant temperamental characteristics, their relation to infant needs for time alone, and maternal perceptions of these needs are examined via videotapings of the infants' signals of disengagement and engagement. Descriptive data based on three mother-infant dyads suggest that infants clearly signal their needs for rest and disengagement in the first eight weeks, and develop unique patterns of "alonetime" behavior that may be related in part to temperamental differences.

Mental rotation: a task for the assessment of visuospatial skills of children.

7 girls and 5 boys, ranging in age from 7 to 12 years, participated in the pilot testing of a mental rotation task developed for use in a comprehensive test battery of visuoperceptual abilities. Two asymmetric, three-dimensional objects were constructed from wood strips such that one object was the mirror-image of the other. Black and white photographs were taken of these objects in various spatial orientations along a horizontal plane. 16 photographs depicted the object right-side-up and in 16 the object was upside-down (rotated 180 degrees in the vertical plane). These photographs were presented to the children who were asked to match each with the corresponding object. Analysis indicated correct judgements of the right-side-up images occurred more frequently than the upside-down images (t11 = 4.73, p < .001). Using these data, adjustments were made to the task instructions to provide greater clarity for the young participants.

Ifosfamide and docetaxel in non-small cell lung cancer.

Ifosfamide has been in use for several decades and is generally considered to be one of the most effective drugs for the treatment of non-small cell lung cancer (NSCLC). At the same time, docetaxel is one of the new, promising drugs with high antitumor activity in various solid tumors. In NSCLC, an objective remission rate of 33% could be achieved in chemotherapy-naive patients. Currently, clinical research with docetaxel in NSCLC patients focuses on various combinations of this drug with radiotherapy and a number of different cytostatic chemicals. There are good reasons for combining docetaxel with ifosfamide. In addition to the promising antitumor activity in NSCLC displayed by both drugs, it is an advantage that docetaxel and ifosfamide have only minimal overlapping nonhematologic toxicity. Moreover, the combination seems to be well founded due to the lack of cross-resistance between docetaxel and alkylators such as ifosfamide of the oxazaphosphorine type, which have shown synergistic antitumor activity in vivo. Based on this background, two phase I studies of docetaxel and ifosfamide have been initiated.

Group psychotherapy with inner-city grandmothers raising their grandchildren.

A year-long psychotherapy group consisting of two co-therapists and eight grandmothers who were parenting their daughters' children is presented. Three models that correspond to the co-therapists' psychoanalytic developmental orientation were used to describe the group phases of development. A number of themes that emerged at different points in the group's life are delineated. They include: authority, control, sibling rivalry, the generation gap, dealing with schools, illness and mortality, isolation, defensiveness, anger, fear of going crazy, guilt, shame, separation, and abandonment. Transference and countertransference issues are also discussed.

Children of adolescent mothers: are they at risk for abuse?

Adolescent mothers are typically depicted as inadequate parents. Their children are thought to be at significant risk for maltreatment. A review of the literature, however, reveals that a confluence of factors other than maternal age are implicated. Many studies make comparisons between teenage and older mothers without identifying the sample's socioeconomic group. The degree of risk to children of adolescent parents may well be determined by the financial, social, and emotional stresses these families face, with availability of resources which offer support and encouragement perhaps being the critical factor. The technique of "mapping" might be used to isolate these correlates. The authors suggest a reformulation of the question of adolescent parental ability, focusing on conditions under which adolescent parents may be at greater or lesser risk of maltreating their children. This approach could ultimately prove conducive to planning and implementing effective intervention programs.

[Immunohistological differentiation of the cells of the arterial wall in transplanted kidneys]. / Immunhistologische Differenzierung der Zellen in der Arterienwand von Transplantatnieren.

22 nephrectomy specimens of renal allografts in chronic rejection after 3 months to 96 months were studied immunohistologically. The various cell types in the arterial wall were characterised with specific antibodies against different cells of the mononuclear phagocyte system, against smooth muscle cells, and for differentiating lymphatic cells. In addition, the metabolism of lipoproteins was studied using different antibodies against several apolipoproteins. According to our results, subendothelial plaques of foam cells consist of macrophages in foamy transformation. In the stage of intimal fibrosis, smooth muscle cells are more prominent. Lymphatic infiltration consists almost exclusively of T lymphocytes. Apolipoprotein analysis reveals deposits of Apolipoproteins A1 and B, mostly extracellular. On the whole, these results show that not only immunologic factors are involved in the reaction of the arterial wall in chronic transplant arteriopathy, but that like in atherosclerosis, disorders of lipoprotein metabolism, probably due to endothelial dysfunction, play an important role.