Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors

PURPOSE: To evaluate the therapeutic effect of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) and unlabeled MIBG in patients with carcinoid tumor. MATERIALS AND METHODS: A therapeutic dose of 7.4 GBq (200 mCi) 131I-MIBG infused over 4 hours was administered to 30 patients with either carcinoid syndrome (n = 20) or tumor symptoms such as pain and fever due to carcinoid tumor (n = 10). In general, two courses were given, 6 weeks apart. Due to radioactivity, patients had to be isolated for 5 to 7 days. Subsequently, we studied the effect of unlabeled MIBG based on the possible pharmaceutic activity of MIBG and to avoid the isolation procedure. A doseescalation study of 8.5, 17, and 34 mg/m2 MIBG infused over 4 hours at 4-week intervals was performed in 20 patients with carcinoid syndrome who were not suitable for treatment with the radioactive compound. RESULTS: Following 131I-MIBG treatment, symptomatic responses were observed in 60% of patients (median duration, 8 months; maximum, 2 years). Side effects were mild and rapidly reversible in 16 patients, and were related to the isolation procedure in seven of these patients. Unlabeled MIBG resulted in symptomatic improvement in 60% of patients (median duration, 4.5 months). Side effects, which included changes in blood pressure, were mild and transient. Symptomatic responses were not accompanied by biochemical responses. CONCLUSION: Both MIBG treatment regimens were equally effective in the palliation of symptoms, but duration of response tended to be much longer with the radioactive compound. However, the unlabeled compound provided a simpler treatment, eg, in elderly patients and those in poor condition, without the need for isolation.     

Immunogenic properties of an anti-DNA antibody-derived peptide, 88H.64-80: location of a dominant idiotope defined by T and B cells

Plasma interleukin-1 beta (Il-1 beta) interleukin-6 (Il-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in 26 women with Anorexia Nervosa (AN), nine of the restricted type (AN-R) and 17 of the binge-eating/purging type (AN-BP), in 24 women with Bulimia Nervosa (BN) and in 26 healthy age- and sex-matched controls. Concentrations of the cytokines were measured at the beginning of the study before starting any treatment and then after 1 and 3 months of combined cognitive-behavioral and pharmacological therapy (fluoxetine for AN-R and AN-BP, amineptine for AN-BP and BN, and fluvoxamine for BN). Basal values of Il-1 beta, Il-6 and TNF-alpha, were the same in patients and controls and did not change during treatments, in spite of the improvement of the mental disorders. This seems to exclude the possibility that alterations of basal plasma cytokine secretion are involved in the etiopathogenesis of AN and BN.     

Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons

IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-alpha2a and IFN-alpha2b were approved for the treatment of hairy cell leukemia just 11 years ago. Today, alpha-IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases. Although the exact mechanism of action of IFN-alpha in the treatment of such diseases is not fully understood, many advances have been made in the characterization of the physicochemical and diverse biological properties of this highly pleiotropic cytokine. Here we review recent developments in our understanding of the antiviral and immunoregulatory properties of IFN-alpha, the nature of the multisubunit IFN-alpha receptor, and the molecular mechanisms of signal transduction. Where available, we have included comparative data on recombinant alpha-IFNs derived from both naturally occurring and nonnaturally occurring synthetic genes. We also review clinical data and data on the side effects and antigenicity of different sources of recombinant alpha-IFNs in humans. These latter topics are of clinical interest, because they may potentially affect the efficacy of these various products. Hopefully, what is already known about IFN will prompt further exploration into the mechanism(s) of action of IFN-alpha and thus deliver new applications for this prototypic cytokine, whose full therapeutic potential is yet to be realized.     

A critical experiential teaching strategy: student and faculty participation in an AIDS walk

The authors report their experience in the placement of a new Nitinol stent. Thirty eight stents were placed in 28 iliac arteries, 3 superficial femoral arteries, 1 popliteal artery, 2 subclavian arteries, and 2 veins of hemodialysis fistulae. The primary success rate was 100%, but several angioplasty balloons have been ruptured due to the specific configuration of the stent. The mean follow-up period was 6 months. Memotherm placement is an easy procedure, but the specific structure of the device makes the manipulation of the angioplasty balloons delicate, especially in tortuous vessels.     

Cerebral hemodynamics and oxygenation in preterm infants after low-vs. high-dose surfactant replacement therapy

In thirteen preterm infants receiving surfactant (Curosurf) replacement therapy, changes in cerebral hemodynamics and oxygenation were investigated by near infrared spectroscopy. Surfactant instillation led to an instantaneous increase in cerebral blood volume (CBV) in all infants, which was primarily due to an increase in deoxygenated hemoglobin. Five infants received a low dose (100 mg/kg = 1.25 ml/kg) of surfactant and 8 a high dose (200 mg/kg = 2.50 ml/kg). A significantly larger increase in CBV was observed in the infants receiving a high dose compared to those receiving a low dose of surfactant. We conclude that cerebral perfusion is affected more after the instillation of a high dose compared to a low dose of surfactant.     

Cytoskeletal sheets of mammalian eggs and embryos: a lattice-like network of intermediate filaments

The interaction between Leishmania parasites and Th1 cells is investigated using a simple mathematical model of immunological responses and parasite population growth within the host. The model generates patterns of resistance and susceptibility to infection that mirror observed trends in experimental infections of mice and of humans exposed to infection in areas of endemic transmission. The heterogeneity in outcome predicted by the model can arise either through differences in the values of the parameters that characterize the genetic background of the host or as a consequence of differences in the size of the infecting inoculum of the parasite. Detailed analyses of equilibrium states and of the time course of infection within a host suggest that a limitation in the availability of precursor T-cells, as a consequence of high levels of recruitment into the activated pool, may play a significant role in the progression of infection in susceptible hosts. A brief discussion is presented of the implications of model prediction for therapeutic intervention.     

An outbreak of hepatitis A during a military field training exercise

Current practice for the selection of unrelated donors involves serological typing of HLA-A, -B and -DR antigens, DNA analysis of the class II region and the MLR. However, even after matching for the class II loci at the DNA level, a significant proportion of matched unrelated pairs remain MLR reactive. Ideal matching for BMT would be a match for the whole MHC haplotype rather than individual HLA loci. In the present study, we have evaluated the complementary role of class III typing in determining MHC identity. A group of 86 donor/recipient pairs, of which 14 were unrelated, was investigated using C4, Bf, HSP70 and TNF DNA probes. Phenotypically HLA-matched siblings were always identical at the C4 locus which is the most polymorphic of all the loci examined. Nine of the 14 HLA serologically matched MLR non-reactive (RRI < 20%) unrelated pairs had class III mismatching. Four of these pairs with class III mismatching were matched at the DRB and DQB loci by RFLP analysis. These results demonstrate that serological identity, DRB/DQB RFLP-matching and a negative MLR do not always match the whole haplotype in unrelated pairs. It can be concluded that the linkage of the class III loci to both HLA regions makes this region a reliable marker of the whole MHC haplotype.     

Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?

PURPOSE: To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD: A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS: None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION: In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.     

Abnormal activation of lipoprotein lipase by non-equilibrating apoC-II: further evidence for the presence of non-equilibrating pools of apolipoproteins C-II and C-III in plasma lipoproteins

Using artificial triglyceride emulsions, we have demonstrated the presence of non-equilibrating pools of apolipoproteins C-II and C-III in human plasma lipoproteins. As the concentrations of acceptor triglycerides were increased, a greater fraction of both apoC-II and apoC-III shifted away from the native plasma lipoproteins to the artificial lipid emulsions. All of the apoC-II and apoC-III in very low density and high density lipoproteins (VLDL and HDL), however, could not be removed from native plasma lipoproteins. The percent of total plasma apoC-II and apoC-III that could be recovered in the VLDL and HDL density fractions varied when plasma from different individuals was used. When plasma samples from normotriglyceridemic subjects were used, HDL was the primary donor of apoCs. The percent of total plasma apoCs associated with HDL decreased from 60% to 25% for apoC-II and from 65% to 15% for apoC-III. When plasma samples from hypertriglyceridemic subjects were incubated with artificial lipid emulsions, VLDL was the primary donor of apoCs. HDL from hypertriglyceridemic subjects only accounted for 5-10% of total fasting plasma apoCs and did not contribute significantly to the final apoC contents of the artificial triglyceride emulsions. To evaluate the significance of the depletion of exchangeable apoCs from plasma HDL, we also examined the ability of control and apoC-depleted HDL to serve as activator for bovine milk lipoprotein lipase (LPL) in vitro. When HDL depleted of exchangeable apoCs were used as the source of plasma apolipoproteins for the activation of LPL in vitro, only 5-10% of the maximal activity obtained with native HDL was demonstrated. In fact, in the presence of comparable concentrations of HDL apoC-II, activation of LPL was the least with HDL which lacked exchangeable apoCs. Our data thus indicated that the presence of exchangeable apoC-II on HDL is necessary for the activation of LPL in vitro. This finding is consistent with our data that suggest that HDL from hypertriglyceridemic subjects do not stimulate LPL as well as HDL from normolipidemic subjects.