Gastroduodenal cytomegalovirus infection is common in kidney transplantation patients

OBJECTIVE: Cytomegalovirus (CMV) infection is known to cause ulcerations, erosion and mucosal haemorrhage in the gastrointestinal tract. The aim of this study was to report the CMV findings in the gastroduodenal mucosa of kidney transplantation patients and immunocompetent controls. MATERIAL AND METHODS: Forty-six kidney transplant patients with upper gastrointestinal symptoms and 43 immunocompetent, dyspeptic patients (controls) prospectively underwent oesophagogastroduodenoscopies (OEGDs), with biopsies from the duodenum and stomach. CMV was demonstrated by immunohistochemistry, both in frozen sections using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein) and in paraffin sections by means of a monoclonal antibody against the delayed early protein (p52). RESULTS: CMV was detected in the gastric mucosa in 30% of the kidney transplant patients and in 9% of the controls (p<0.05) and in the duodenal mucosa in 70% and 35%, respectively (p<0.01). The total frequency of CMV findings was similar in patients who underwent OEGDs <1 year and >1 year after transplantation. CMV inclusions were found only in transplantation patients <1 year after transplantation (n=9). CMV findings, especially inclusions, in the gastric biopsies were associated with nausea and upper gastric pain. Histopathological findings in CMV-positive samples were non-specific, focal inflammation in haematoxylin-eosin-stained preparations, while CMV p52 staining showed inclusions in either the epithelial or endothelial cells. CONCLUSIONS: CMV could be detected in the gastroduodenal mucosa in 74% of kidney transplantation patients and in 40% of immunocompetent controls (p<0.01). CMV diagnostics are always recommended when gastroduodenal biopsies of kidney transplantation patients are performed.     

Interferon-alpha and 13-cis-retinoic acid as maintenance therapy after high-dose combination chemotherapy with growth factor support for small cell lung cancer--a feasibility study

This randomized phase II multi-center study was designed to determine the time to progression, duration of response and the feasibility of an intensified maintenance regime consisting of a combination of interferon (IFN)-alpha and retinoic acid after high-dose combination chemotherapy and radiotherapy in patients with small cell lung cancer. The patients received four courses of combination chemotherapy consisting of ifosfamide, carboplatin and etoposide, with higher doses of ifosfamide and carboplatin given in the first course, with routine growth factor support. Responding patients were then randomly assigned to one of three maintenance therapy arms. All patients with limited disease (LD) were given thoracic radiotherapy before maintenance therapy and those who had also achieved a complete response (CR) or minimal residual disease (MRD) received prophylactic cranial irradiation. In Arm 1 patients received IFN-alpha-2a, 6 MIU s.c. TIW for 4 weeks, followed by 3 MIU s.c. TIW, and 13-cis-retinoic acid 1 mg/kg/day p.o. BID daily. In Arm 2 patients received trophosphamide 100-150 mg/day p.o. BID. No maintenance treatment was given in Arm 3, the control group. Maintenance therapy was continued for 1 year. Eighty-five patients were treated according to the protocol. Twenty-one patients achieved CR, four achieved MRD and forty-two achieved partial responses to chemotherapy and radiotherapy. Sixty patients (71%) were randomly assigned for maintenance treatment. Median survival was 17.1 months in the IFN-alpha-retinoic acid arm, 12.4 months in the trophosphamide arm and 13.5 months in the control arm. One-year survival rates were 82, 56 and 55%, respectively. Duration of response was 6.5, 5.5 and 4.7 months, respectively. Time to progression was 8.6, 8.0 and 6.8 months, respectively The differences were not statistically significant. The IFN-alpha-retinoic acid maintenance treatment was well tolerated. Patients who received IFN-alpha-retinoid maintenance therapy lived longer after the onset of progressive disease. The treatment regime was effective, feasible and well tolerated.     

The Effect of Parenting Stress on Fathers' Availability and Engagement

The present study was designed to shed light on the relation between parenting stress, father's alcohol use, child characteristics and father's engagement and availability. The study cohort comprised 821 fathers of preschool children in Finland. Parenting stress and child's mood, acceptability and demandingness were related to father's engagement to the preschooler and to the extent of the father's availability. Parenting stress began a cycle of alcohol abuse and child-negative characteristics, and eventually led to a decrease in joint father-child activities, father's feeling of compulsory engagement, daily conflict situations, difficulty in including the child in everyday activities and a reduction in the amount of time spent directly or indirectly together.     

Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB-IV non-small-cell lung cancer.

Purpose: To evaluate the efficacy of the combination of vinorelbine and gemcitabine as a non-platinum chemotherapy regimen in patients with inoperable locally-advanced or metastatic non-small-cell lung cancer (NSCLC). Efficacy was assessed primarily in terms of response rate, and secondarily in terms of toxicity, time to progression and survival.Patients and methods: Patients with cytologically- or histologically-proven stage IIIB–IV NSCLC, bi-dimensionally measurable lesions, adequate haematological, hepatic and renal function, WHO performance status 2 and no previous chemotherapy or radiotherapy were eligible. The first 12 patients were entered in a pilot study and received vinorelbine (VNR) 30 mg/m² on days 1, 8, 15 and 22, and gemcitabine (GEM) 1000 mg/m² on days 1, 8 and 15, of a 28-day cycle. Subsequently, patients were entered in a phase II trial of VNR 35 mg/m² and GEM 1200 mg/m² on days 1 and 15 of each 28-day cycle. Treatment consisted of three cycles of the chemotherapy, with a further three cycles for those patients who achieved stable disease or a complete or partial response (CR/PR) to the first three cycles. Patients who had achieved CR or PR after six cycles continued with the treatment until relapse.Results: The dosage and scheduling of VNR and GEM in the pilot study resulted in neutropenia necessitating reductions or delays in treatment, and consequently low dose intensity. The schedule was thus modified to VNR 35 mg/m² and GEM 1200 mg/m² on days 1 and 15 of each 28-day cycle for the phase II trial. Thirty-three patients were enrolled in the phase II trial, and 28 were evaluable for response. The overall intent-to-treat response rate of all 45 patients was 40% (18 of 45), comprising 4 CR (9%) and 14 PR (31%). For the 28 evaluable patients who received the fortnightly chemotherapy the response rate was 46% (13 of 28), CR 11% (3 of 28) and PR 36% (10 of 28). Seven patients (25%) had stable disease. The one-year cumulative survival rate for the 33 patients receiving the fortnightly chemotherapy was 24% and median time-to-progression 4 months (range 1–16 months). Median survival for these patients was eight months. Nine out of twelve patients in the pilot study (75%) suffered grade 3–4 neutropenia. There was one toxic death, attributed to neutropenic fever and sepsis, and two cases of pulmonary embolism. One patient suffered Grade 4 thrombocytopenia. Only eight patients (24%) on the fortnightly schedule suffered grade 3–4 neutropenia, resulting in dose reductions or delays for three of them (9%). None of the patients on the fortnightly schedule suffered thrombocytopenia or anaemia.Conclusions: The fortnightly schedule of gemcitabine and vinorelbine was a well-tolerated out-patient regimen, producing response and survival rates comparable to those of cisplatin combination regimens, but with a more favourable toxicity profile. Gemcitabine and vinorelbine should now be tested in a triplet combination with a taxane as the third drug, or against a platinum-containing regimen in a phase III study.