Assessment of palliative chemotherapy: a step beyond response

In summary, tumour response is a useful index of cytotoxic activity, but is of limited value in the assessment of benefit to the patient following treatment with cytotoxic drugs. Survival is a similarly inappropriate endpoint to assess the clinical benefits of palliative cytotoxic therapy. The widespread introduction of QL assessment as a primary outcome measure in cancer therapy will enhance our understanding of the value of a wide range of established cancer treatments, not only that of palliative chemotherapy, but also surgery and radiotherapy.     

Laparoscopic cholecystectomy in acute cholecystitis

Laparoscopic cholecystectomy was fulfilled in 108 patients admitted to the clinic with acute cholecystitis. Operations were made on 73% of them during the first four days from the beginning of the disease, 18.5% were operated upon within 5-7 days, 8.5% - 8 days later. Endoscopic papillotomy with removing the stones from the choledochus was performed in 10% of the patients before operation. Serious problems during taking the gallbladder from the inflammatory infiltration were observed in 29% of the patients. Technical problems took place more often if the patients were operated upon 5 days after the beginning of the disease. Change for open laparoscopy and standard cholecystectomy were necessary in 9 patients (8.3%). There were no lethal outcomes after laparoscopic cholecystectomy. Complications were observed in 12 patients (11.1%). The average period of staying at the hospital was (5.2 +/- 2.1) days. Laparoscopic cholecystectomy can be successfully performed in patients with acute cholecystitis by a sufficiently experienced surgeon.     

Insulin (auto)antibodies from human IDDM cross-react with retroviral antigen p73

In NOD mice, endogenous retroviruses including intracisternal type A particles (IAP) are expressed in the pancreatic beta cells. Furthermore, in these mice, insulin autoantibodies (IAA) cross-react with retroviral protein p73 (the IAP gag gene product), suggesting molecular mimicry between insulin and p73. We therefore investigated whether IAA and insulin antibodies (IA) associated with human IDDM cross-reacted with p73. Fifty IAA positive sera from 30 newly diagnosed IDDM before insulin therapy and 20 non-diabetic first degree relatives of IDDM and 27 IA positive sera from insulin treated IDDM, initially defined as IAA or IA positive by radioimmunoassay, were evaluated. Binding to insulin and to p73 of these sera were analysed by ELISA. Approximately 65% of sera which bound insulin by ELISA also bound p73. Only one sample negative for insulin binding was positive for p73 binding. Preabsorption with either insulin or p73 inhibited binding to both insulin and p73. However, preabsorption with mouse hemoglobin had no effect on their binding. Repeat measurement of binding to insulin and p73 in 10 non-diabetic first degree relatives of IDDM over an average of 16.6 months showed that each individual's reactivity to insulin and to p73 was relatively stable over time. Furthermore, in different individuals, binding to p73 and to insulin was closely correlated over time. In addition, 75 healthy teenagers (IAA negative by RIA) were used as normal controls in this study. p73 binding was found in only two (2.7%) of the 75 subjects. These results indicate that approximately 65% of ELISA (+) IAA and IA subjects have antibodies which recognize both insulin and p73, suggesting that IAA and IA from some subjects recognize an epitope shared between human insulin and the murine gag gene product. This raises the possibility that for some subjects who are IAA positive, the immunizing antigen may be antigenically similar to p73, rather than insulin, and that endogenous retroviruses may be involved in human IDDM.     

Two measures of nurses' attitudes toward abortion as modified by experience

Random samples of nurses in two states which differed in abortion statues were sent questionnaires. Content areas included experience with 12 specific nursing activities associated with abortion, willingness to participate in the same activities, and extent of agreement with statements related to abortion. Attitudes toward abortion were inferred from the willingness-to-participate items and from the agreement section. These two measures correlated highly suggesting a common underlying dimension. However, the two samples differed significantly in extent of agreement but did not differ in willingness to participate. These results were interpreted as supporting the position that attitudes derived from items using situational contexts might bear a better relationship to behavior. The findings also suggest that abortion facilities can probably be staffed without violating personal preferences since so many expressed willingness to participate in at least some of the activities. Comparison across the two samples suggest that increased experience or even the potential for experience with abortion patients tended to increase the favorableness of attitudes toward this issue.     

Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor

Filarial nematode parasites establish long-term chronic infections in the context of an antiparasite immunity that is strongly biased toward a Th2 response. The mechanisms that lead to this Th2 bias toward filarial antigens are not clear, but one possibility is that the parasites produce molecules that have the capacity to proactively modify their immunological environment. Here we report that filarial parasites of humans secrete a homologue of the human proinflammatory cytokine macrophage migration inhibitory factor (MIF) that has the capability of modifying the activity of human monocytes/macrophages. A cDNA clone isolated from a Brugia malayi infective-stage larva expression library encoded a 12.5-kDa protein product (Bm-MIF) with 42% identity to human and murine MIF. MIF homologues were also found to be expressed in the related filarial species Wuchereria bancrofti and Onchocerca volvulus. Bm-mif was transcribed by adult and larval parasites, and the protein product was found in somatic extracts and in the parasite's excretory-secretory products. Immunohistocytochemistry revealed that Bm-MIF was localized to cells of the hypodermis/lateral chord, the uterine wall, and larvae developing in utero. Unexpectedly, the activities of recombinant Bm-MIF and human MIF on human monocytes/macrophages were found to be similar. When placed with monocytes/macrophages in a cell migration assay, Bm-MIF inhibited random migration. When placed away from cells, Bm-MIF induced an increase in monocyte/macrophage migration that was specifically inhibited by neutralizing anti-Bm-MIF antibodies. Bm-MIF is the first demonstration that helminth parasites produce cytokine homologues that have the potential to modify host immune responses to promote parasite survival.     

Magnetic resonance imaging correlates of depression in early- and late-onset Alzheimer''s disease

Even today psychotic depression is connected to a lot of unanswered questions. A self-questionnaire (BFD) was developed in order to evaluate cognitions corresponding to mood congruent depressive delusions. They were assumed to indicate psychotic depression and to be related to severity of the depressive syndrome. 42 depressed inpatients were examined by the BFD, the Hamilton Depression Scale (HAMD) and the Beck Depression Inventory (BDI). BFD scores were found increased in psychotic depression (p = 0.009) and correlated to BDI scores (p = 0.002). 19 re-examined patients showed a significant improvement in HAMD and BDI scores but not concerning the delusion indicating cognitions (BFD), which were significantly correlated to suicidality items of BDI and HAMD (p = 0.005). The results prove the delusion indicating nature of cognitions measured by the BFD and their correlation to severe depression. Differences in treatment response are indicated and persisting or increasing BFD scores seem to be accompanied by more severe suicidal tendency.