Absence of response: a study of nurses' experience of stress in the workplace

It has become clear that nursing is a high-risk occupation with regards to stress-related diseases. In this study, we were interested in nurses' experiences of stress and the emotions arising from stress at work. Results showed that nurses experienced negative stress which was apparently related to the social environment in which they worked. Four nurses were interviewed. The method used was grounded theory. Analysis of the interviews singled out absence of response as the core category. Recurring stressful situations obviously caused problems for the nurses in their daily work. Not only did they lack responses from their supervisors, they also experienced emotions of frustration, powerlessness, hopelessness and inadequacy, which increased the general stress experienced at work. Our conclusion is that the experience of absence of response leads to negative stress in nurses.     

Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

Therapeutic vaccination with dendritic cells (DC) can lead to tumor regression in animal models and has shown promising results in the first clinical trials of metastatic renal cell carcinoma and malignant melanoma. In vitro data and results of a clinical phase I/II trial using DC tumor fusions in patients with progressive metastatic renal cell carcinoma are presented here. In addition to toxicity and feasibility, complex immune monitoring was a point of interest. DC precursor cells were obtained from the peripheral blood mononuclear cells (PBMCs) of healthy donors and were fused with either allogeneic (8 patients) or autologous (4 patients) renal tumor cells. In total, 12 patients with progressive metastatic renal cell carcinoma were treated with an average of 2.8 x 10(7) tumor cells fused with 1.8 x 10(7) DC each administered on days 0, 28, and 56 intradermally. Fusion efficacy for the tumor cells used was 14.3% +/- 7.8%. Cell viability was 59.8% +/- 6.8% after fusion and irradiation. We observed no adverse effects and no difference in clinical outcome between the allogeneic and the autologous treatment. Eight patients remained in a progressive disease state and four patients in a stable disease state. T-cell immunity was carefully monitored before, during, and after treatment. Delayed-type hypersensitivity (DTH) reaction using tumor cells was positive after treatment in 7 of 12 patients, 2 of whom were found to have stable disease. An increase in the reactivity against recall antigens was seen in most patients. Interestingly, cytotoxicity of peripheral blood lymphocytes (PBLs) against renal cell carcinoma cells increased during treatment as well as the percentage of interferon-gamma-secreting cells. This effect was significantly enhanced within the group that had stable disease. The lack of adverse effects together with positive immunologic signs justifies further investigation of this novel therapeutic approach. Further studies are necessary to test for clinical effectiveness in patients with tumors, especially those with less advanced disease.     

Phosphinic peptide inhibitors of macrophage metalloelastase (MMP-12). Selectivity and mechanism of binding

Pseudopeptide inhibitors of MMP-12 with a phosphinic dipeptide G psi[PO(2)H-CH(2)]L covering the P1-P1'- positions originating from a combinatorial solid phase library have been identified and kinetically analysed with respect to binding mechanism and selectivity towards MMP-7, MMP-9, MMP-13 and MMP-14. One compound with a low nanomolar dissociation constant for MMP-12 showed significantly lower affinity towards all other MMPs tested compared to MMP-12. Two compounds showed selectivity against MMP-9, MMP-13 and MMP-14. One additional compound showed selectivity against MMP-7. The selectivity of these compounds could partly be rationalized by analysis of homology models of the enzymes. Truncated versions of one inhibitor spanning P2 to P2', P3 to P2' or P2 to P3' showed that interactions on both the prime and the non-prime side are important for binding. A two-step binding mechanism, with a rate limiting second step, was shown for binding of a tryptophane containing inhibitor to MMP-12 by transient state analysis, using the tryptophane residue of the inhibitor as fluorescent probe.     

Adult primary teratoma of the testis – report on 5 cases in clinical stage I disease

Objectives:Testis pure teratoma accounts for 2.7% to 3% of all germcell tumors in adult where it behaves as a malignant neoplasm. Pureteratoma of the testis presents in clinicalstage I disease in 44% of thepatients whose risk of having pathologicalstage II disease is 16.7% to19.2%. Herein we report on 5 casesof adult pure teratoma of the testispresenting itself in clinical stage I disease.Materials and methods: From September 1976 to February 2000, 75patients underwent orchidectomy for clinical stage I nonseminomatous germcell cancer of the testis. Testis pure teratoma was detected in 5 patients(7%). Testis tumor markers wereevaluated in all cases. Patients underwentimaging examination to detect the clinical stage of the disease. Treatmentoptions after orchidectomy included retroperitoneal lymph node dissection(RPLND) in 4 patients and surveillance in 1.Results: The average age of the patients was 31 years (range 24–45).The tumor was on the left sided in 3 cases(60%) and right in 2 (40%).Tumor average size was 3.2 cm (rang 1–6).Histopathology detected thefollowing subtypes: mature teratoma in3 cases (60%), immature teratomain 1 (20%) and teratoma with malignanttransformation in (20%). Allpatients were at clinical stage I disease. Germ cell cancer microscopicmetastatic disease including embryonal carcinoma was detected in 1dissected lymph node of 1/4 patients (25%).Average follow up was 166months (range 93–249). All patients werealive and disease free and norelapses were detected during the follow up period.Conclusions: Primary pure teratoma of the testis does not respond tochemotherapy nor does it to radiation therapy. The disease treatmentoptions after orchidectomy for patients withclinical stage I disease includeRPLND or surveillance with their relativerisks and benefits. RPLND is thechosen treatment because it is both staging and treating. A close a longterm follow up is required since pure teratoma metastatic disease mayclinically develop after more than 10 years.     

Adrenal extramedullary hematopoiesis: Report on a pediatric case and update of the literature

The authors report on a rare pediatric case of adrenal extramedullary hematopoiesis in a patient with beta-thalassemia disease. The lesion was clinically discovered as incidentaloma of the right adrenal gland and treated by surgery. Adrenal extramedullary hematopoiesis may clinically be detected as incidentaloma. Adrenal incidentalomas presenting with hematologic disorders, such as agnogenic myeloid aplasia and beta-thalassemia, need careful imaging as well as adrenal hormonal investigation in order to exclude malignancy and sublinical hypersecretory syndromes. Ultrasound or CT-FNA of the lesion are effective in finding out the disease.     

Short-term steroid therapy, sometimes with long-term sequelae

Two patients developed osteonecrosis, respectively one and two years after the short-term intravenous use of dexamethasone. A 35-year-old man received 150 mg over a period of 3 weeks associated with a craniotomy for a subarachnoidal haemorrhage. He developed bilateral osteonecrosis of the femoral and humeral heads, which necessitated bilateral hip replacement surgery. He still experiences pain in both shoulders. A 45-year-old woman received 42.5 mg over a period of 1 week as a treatment for reflex dystrophy with oedema. She developed bilateral osteonecrosis in the femoral condyles, the talus and the calcaneus and after treatment she continued to experience pain in her right knee and ankle whilst walking. The only other risk factor for osteonecrosis identified in these patients was hyperlipidaemia in the man. Corticosteroid-induced osteonecrosis is typically multifocal and usually occurs 0.5 to 3 years after the therapy was initiated. There is a relationship with the dose and length of therapy. Even the short-term use of corticosteroids for 3 weeks or less, may lead to this dehabilitating complication.     

Molecular genetic alterations in glioblastomas with oligodendroglial component

Glioblastoma multiforme is the most malignant astrocytic glioma and usually resistant to chemotherapy. A small fraction of glioblastomas may contain areas with histological features of oligodendroglial differentiation. To determine the molecular genetic alterations in such "glioblastomas with oligodendroglial component", we investigated 13 of these tumors for genetic alterations and/or expression of the TP53, CDKN2A, PTEN, and EGFR genes. In addition, we performed microsatellite analyses for loss of heterozygosity (LOH) on chromosome arms 1p, 19q and 10q. None of tumors showed evidence for LOH on 10q. LOH on 1p was detected in 3 tumors, 1 of which additionally showed LOH on 19q. The 3 tumors with LOH on 1p showed neither TP53 mutations nor nuclear p53 accumulation. In contrast, 9 of 10 tumors without demonstrated losses on 1p showed nuclear p53 accumulation. TP53 mutations were identified in 3 of these cases. Further aberrations detected were epidermal growth factor receptor (EGFR) overexpression (3 of 13 tumors), homozygous CDKN2A deletion (2 of 11 tumors), and PTEN mutation (1 of 13 tumors). Taken together, our results indicate that "glioblastomas with oligodendroglial component" carry heterogeneous genetic alterations. LOH on 10q, PTEN mutation, and homozygous CDKN2A deletion appear to be less common in these tumors as compared to ordinary glioblastomas. Furthermore, a subset of these tumors demonstrates LOH on 1p, i.e., an alteration that has recently been linked to chemosensitivity and good prognosis in anaplastic oligodendrogliomas.     

Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic ovary syndrome: a pilot prospective study

The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to a decrease of insulin secretion. Further randomized studies should be performed in order to obtain significant conclusions on the possible clinical application.     

False-negative HIV antibody test results

Ideally HIV antibody tests have to be both extremely sensitive and able to recognize all known HIV subtypes. Three patients whose sera failed to react with a synthetic oligopeptide-based HIV antibody test are described in this report. The patients were a Pakistani male infected recently, an Australian male infected for several years, and a Ugandan woman with AIDS. The presence of anti-HIV antibodies was confirmed by means of a standard algorithm with different assay formats. All three sera failed to react in one antiglobulin enzyme-linked immunosorbent assay (ELISA) (Bioelisa HIV-1+2, Biokit SA). No single underlying reason could be identified for the assay failure in the three cases. The first patient, probably infected recently when first tested, was strongly positive by the same assay a year later, confirming the relative insensitivity of oligopeptide assays reported previously for detecting the early antibody response. The other two patients appear to have been infected for several years. Although unlikely to have been infected with a non-clade B virus, the sample from patient 2 lacked detectable antibody to the transmembrane glycoprotein (gp41), the site of the synthetic oligopeptides. Patient 3, of Ugandan origin, was found to be infected with a non-clade B virus. Although her serum reacted strongly to subtype B gp41 in Western blot, it failed to react in the antiglobulin ELISA. Since there appears to be no single common explanation for these three failures there is little opportunity to identify prospectively those situations where testing using assays employing synthetic oligopeptides on the solid phase is likely to fail.