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Background: Gastrointestinal side effects are commonly associated with opioid treatment for pain., Aim: To understand gastrointestinal side effects associated with opioid treatment., Methods: This study was a population-based survey of adults in the US who use opioids to manage pain unrelated to cancer. Participants were recruited from an existing Web-enabled panel and a supplemental panel of individuals who previously indicated an interest in participating in Web-based surveys., Results: Overall, 2055 individuals participated in the main phase of the survey. Fifty-seven per cent of participants reported having had constipation that they associated with opioid treatment, and 49% reported constipation in the previous 4 weeks. Thirty-six per cent of participants reported new or worsening constipation in the previous 4 weeks. Thirty-three per cent of participants reported constipation as their most bothersome symptom associated with opioid treatment, 13% reported nausea, 11% abdominal pain and 10% gas. Seventy-three per cent of the participants who reported any GI symptoms did not change the dosage level or frequency of use of opioids because of adverse events, which may be explained by the fact that 72% of participants used over-the-counter laxatives and 12% a prescription laxative., Conclusion: Constipation is a frequent and significant event occurring with opioid use.

In 2003, the Office of Juvenile Justice and Delinquency Prevention (OJJDP) provided Florida's Department of Juvenile Justice (DJJ) with a $3.5 million grant to design and implement a faith- and community-based program for incarcerated juveniles. Florida's experience developing a completely new program has provided valuable lessons regarding important issues to consider and address before clients are referred to the program. This article enumerates 10 key lessons from Florida's experience that can provide important guidance to other sites across the country hoping to develop faith-related services for youths in institutions.

Batch tests of benzene degradation were performed in liquid phase at 30 degrees C, pH 6.8 +/- 0.2, and 200 rpm in two 3-L stirred tank bioreactors, using the benzene-degrading bacterium Pseudomonas sp. NCIMB 9688. A relatively high starting biomass level (220-270 mg(X)/L) and starting benzene concentration ranging from 20 to 200 mg(S)/L were selected as conditions to investigate possible inhibition phenomena. Volumetric as well as specific rates of biomass formation and substrate consumption were calculated from experimental data of both growth and benzene degradation and used to propose and check a new overall kinetic model for cell growth simultaneously accounting for both product and substrate inhibitions. The results of the present study evidenced the occurrence of a competitive-type product inhibition due to 2-hydroxymuconic semialdehyde (K(iP)' = 0.902 mg(S)/L), which was stronger than the uncompetitive-type inhibition exerted by substrate (K(iS) = 7.69 mg(S)/L).

Speech restoration after circumferential pharyngolaryngectomy with free jejunal repair for advanced tumors of the hypopharyngo-esophageal tract remains a difficult problem to solve. We report here the results of secondary voice restoration in six patients who received a Provox 2 type prosthesis and intensive speech therapy after circumferential pharyngolaryngectomy with free jejunum repair. No patient had operative or post-operative complications due to insertion of the prosthesis. No patient had to have the prosthesis removed during the follow-up (8 to 14 months). Analysis of some acoustic parameters of voice (fundamental frequency, waveform perturbations) and qualitative characteristics of speech (intelligibility, pleasantness and acceptability) demonstrated that all the patients were able to produce satisfactory speech after tracheojejunum puncture and speech therapy and were satisfied with their own ability to communicate. Our results are reassuring and we therefore advise that in patients undergoing free jejunum flap reconstruction of the hypopharyngo-esophageal tract voice restoration should be attempted by placing a voice prosthesis through a secondary tracheo-esophageal puncture and providing intensive speech training.

Background and Objectives: Oropharyngeal carcinoma tends to be aggressive and deeply infiltrative of nearby sites, with an high incidence of lymph node metastases. The last treatment decision generally depends on the stage of the lesion and the patient's general status. Oropharyngeal tumor is generally treated by integrated treatments., Methods: We retrospectively studied 115 patients with locally advanced oropharyngeal tumors treated in our institution with combined therapies compare the results in two different groups of patients (surgery plus radiotherapy and chemotherapy plus radiotherapy)., Results: The 3-year overall survival rate in patients who underwent surgery plus radiotherapy was 82% and in those who underwent chemotherapy plus radiotherapy was 49%., Conclusion: The results suggest that surgery followed by radiotherapy seems to be the best treatment in the case of locally advanced oropharyngeal tumor., (Copyright 2000 Wiley-Liss, Inc.)

Aims: Over the last years, the management of patients with head and neck cancer has become extremely complex, and the knowledge and information needed to care for a patient can no longer be trusted to the memory or manual systems. Recent advances in data processing technology offer the potential for creating ideal instruments to organize, store and analyze such information., Methods: We developed a computerized database management system (H&N-CDMS) which fulfils the following requisites: easy to use even by operators not expert in informatics; minimum possibility of insertion of ambiguous data; use for clinical and research purposes; can be interconnected in a network of similar database operating in other centers; can be expanded to image processing., Conclusions: The configuration of the system is described and its main characteristics are discussed: data entry and coding facilities, data accuracy and standardization, security and anonymity, data retrieval and analysis. H&H-CDMS is a user-friendly tool for head and neck cancer data management in clinical and research environments.

Drunk driving has been a concern for a decade and a half, with most discussions of its control centering on offenders. Research on the extent to which citizens engage in behaviors to avoid becoming victims of drunk drivers, however, is in short supply. This project examines the level of participation in protective behaviors, and it assesses the potential sources of self- and other-protection. Our findings indicate that substantial proportions of citizens take action to protect themselves and others from victimization by drunk drivers. We also find limited support for the fear/victimization model and no support for a collective security explanation of protective behavior.

Benign thyroid nodules is a significant clinical problem since it involves more than 90% of all thyroid surgery. This has led the authors to perform a retrospective study of 190 patients suffering from this pathology out of 299 patients who underwent surgery from 1979 to 1995. 89 total thyroidectomies and 101 radical hemithyroidectomies were performed in patients suffering from benign thyroid nodules. Two cases of recurrent monolateral paralysis were found as well as 3 cases of permanent hypoparathyroidism in those patients who underwent total thyroidectomies. The results of numerous authors as well as the present case review indicate that more radical surgery does not significantly affect the degree of permanent complications. For this reason the authors are convinced that such radical surgery should be the treatment of choice, particularly in young patients whose life expectancy is long and where the likelihood of recurrence is greater.

Different glucocorticoid hormones (GCH) show differences in the intensity and in the kinetics of their immunomodulating activity. The mechanism(s) of action of GCH is under investigation, but is has been noted that they exert immune activity via the genomic pathway. We have studied the effects of prednisone (PDN), deflazacort (DFC), and dexamethasone (DXM) on the production of cytokines (IL-2, IL-6, TNF-alpha, IL-10) by peripheral T lymphocytes, and the effects on the inhibition of NF-kB DNA binding activity by activated Jurkat cell line. The data obtained show that the three GCH molecules exert an immunosuppression on cytokine production by T lymphocytes and a strong decrease in the nuclear translocation of NF-kB in Jurkat cells; moreover, (a) not all the cytokines investigated were affected, and not with the same intensity, by the three GCH and (b) DXM inhibited the binding activity of NF-kB less than that of DFC and PDN. These data are in agreement with the concept that different GCH compounds might differ in their binding and affinity properties, tissue-specific metabolism, and interaction with transcription factor.

Glucocorticoid hormones (GCH) induce apoptosis in PHA-primed peripheral blood T lymphocytes (PBL) and down-regulate membrane-bound proteins involved in the immune response. We have analyzed whether GCH are able to affect the expression of the TCR-associated molecules CD3, CD4, and CD8 on PBL-PHA, and whether the modulation of those receptors is related to the GCH-driven apoptosis of the PBL-PHA. Lymphocytes were cultured with PHA or with PHA plus prednisone (PDN) 10(-3), 10(-6), and 10(-9) M. Then expression of CD2, CD3, CD4, CD8, and CD56 antigens was studied by cytofluorimetric assay using propidium iodide (PI) staining and annexin procedure, and by gel electrophoresis of low molecular weight DNA. PDN, at a pharmacological concentration (10(-6) M), was able to inhibit the CD3 expression on T cells. The kinetics of CD3 decrement and of apoptosis show that the down-regulation of CD3 molecules precedes DNA fragmentation and that the cells lacking CD3 are those prone to PDN-induced apoptosis. The inhibition of CD3 is not related to a transcriptional or posttranscriptional phenomenon, because both PBL-PHA and PBL-PHA-PDN expressed the same amount of intracytoplasmic CD3 molecule. PDN also induced a down-regulation of the CD4 and CD8 molecules that resulted sooner in more intense CD8. In vitro PDN is able to induce apoptosis in PBL-PHA through a down-regulation of CD3 molecules.

IL-15 is an immunostimulatory cytokine sharing with IL-2 the IL-2R beta gamma complex. In vivo, IL-15 detection in synovial fluids has been associated with the development of rheumatoid arthritis. A debate exists as to whether IL-15 has the potential to be secreted in meaningful amounts or to act as a pericellular cytokine. Our data show (1) the presence of two IL-15 isoforms displaying signal peptides of different length and the capacity to be secreted restricted to the isoform bearing the longer one; (2) in cells expressing the two isoforms, the existence of different nuclear localization and intracellular trafficking of IL-15 and IL-15R alpha; and (3) an intercellular microcirculation of IL-15, not detectable with ELISA kits, but displaying a role as an anti-apoptotic factor able to induce the deflection of the TNFR associated factor 2 (TRAF) to IL-15R alpha. Our data point to a juxtacrine mechanism of action of IL-15 and suggest a role for IL-15/IL-15R alpha in the regulation of apoptosis.

GM-IVA is a short and effective induction therapy of non M3 de novo AML including GM-CSF (300 mcg 12 hrs before starting therapy), Ara-C (250 mg/sqm c.i. x 3 days), VP16 (100 mg/sqm x 3 days) and idarubicin (12 mg/sqm x 3 days); it was followed by a fludarabine containing salvage protocol (FLANG). Patients <60 years of age achieving CR received 2 courses of FLANG and autologous or allogeneic BMT when possible. Patients >60 years of age in CR received a second course of GM-IVA. Twenty-one consecutive patients (mean age 64, range 29-85) entered the study. Three patients (14%) died during induction therapy. After one course of GM-IVA, CR was achieved in 12 patients (57%). Two further patients were salvaged with FLANG therapy so that the final CR rate was 14/21 (67%). In elderly patients the final CR rate (62%) is noteworthy, considering that 6 patients were >70 years of age and 3 were >80. All three patients >80 achieved CR (lasting 5 to 7 months). The median time of granulocyte and platelet recovery was 15 days. Our scheme was well tolerated. In the group of elderly patients 3 out of 14 died during induction (21%) and 4 life-threatening infections were observed (28%). The short duration of cytotoxic therapy and perhaps the use of G-CSF contributed to a reduction of the hospitalization period (median of 22 days), thus providing major savings on induction costs and allowing for better utilization of beds as well as significantly improving patients' quality of life.

We have applied a double-determinant immune assay (DDIA) to measure soluble beta2-microglobulin (beta2-micro)-free HLA class I heavy chains in serum. The mean concentration of beta2-micro-free HLA class I heavy chains in serum from 120 healthy subjects was 0.21+/-0.24 microg/ml. The individual serum levels of beta2-micro-free HLA class I heavy chains had a wide distribution, did not seem to be related with HLA phenotype, were stable over time and did not change with age. The serum levels of soluble beta2-micro-free HLA class I heavy chains did not correlate with those of soluble beta2-micro-associated HLA class I heavy chains, suggesting that their release is independently regulated. Three forms of soluble beta2-micro-free HLA class I heavy chains, with apparent molecular masses of 44, 39 and 37-35 kD, respectively, circulate in human serum. These results provide a useful background to assess the serum level of soluble beta2-micro-free HLA class I heavy chains in pathological conditions and to evaluate their putative immunoregulatory function.

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.

In recent years the management and interdisciplinary treatment of oncological patients has become extremely complex due to the progress made in diagnosis and therapy. As a result, the knowledge required to treat patients can no longer be simply memorized or manually filed. Computer technology provides the ideal instrument for organizing, saving and analyzing data from head and neck tumor patients. The authors have prepared a computerized database to meet the following needs: ease of use, even for non computer savvy users; minimal ambiguity for data entry; use for both clinical and scientific purposes; possibility to create a network with similar database at other Centers; possibility to expand to include image management. The archive is based on a personal computer with an INTEL 80486 microprocessor, 40 Mb RAM, DOS 6.0. and Windows 3.1. The software includes four main routines: a) formulation and management of tables where oncological data are gathered; b) entry and management of patient-related clinical data; c) statistical processing for epidemiological and oncological research and; d) management of basic computer services. In clinical practice the database allows the following: a) preparation of a monthly chart of check-ups, b) rapid tracking of patients lost to followup, c) printout of a summary of the clinical history of each patient at the time of check-up and rapid updating at the end of the examination, d) automatic production of forms such as discharge letters and reports to be shared with related services (i.e. medical oncology, radiotherapy). In addition, the database is a powerful, versatile research tool which can promptly provide all sorts of oncological data and can automatically prepare tables, diagrams, correlations, survival curves. The system was developed from 1993 to 1995 and has been operative, with a few minor modifications and updates, since 1995. Today the database contains more than 1200 oncological cases and the system is used daily by medical and paramedical personnel alike. Approximately 15 new cases are entered a month and 80 cases updated after follow-up.

The expression of HLA class I antigens is downregulated in CD4+ T cells following in vitro HIV-1 infection. We determined whether the expression of HLA class I antigens is downmodulated in peripheral blood lymphocytes (PBLs) of HIV-1-positive subjects and whether this defect correlates with disease progression. A cohort of 62 HIV-1-seropositive individuals in different stages of disease was studied. Among these, four subjects were evaluated at yearly intervals for 6 years. The expression of HLA class I, HLA class II, and CD38 antigens was analyzed in PBLs and in CD4+ and CD8+ T lymphocyte subpopulations. The percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in PBLs from HIV-1-positive individuals than in PBLs from HIV-negative controls, proportionally decreased with disease progression, and significantly correlated with the decrease in CD4+ T lymphocytes. Furthermore, the percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in CD4+ T lymphocytes from AIDS patients with respect to CD4+ T lymphocytes from HIV-negative controls and to CD8+ T lymphocytes from HIV-negative controls and AIDS patients. By contrast, the expression of HLA class II and CD38 antigens was upregulated in CD4+ and CD8+ T lymphocytes from HIV-1-positive subjects. The defective expression of HLA class I antigens could impair the lysis of HIV-infected CD4+ cells by virus-specific HLA class I-restricted cytotoxic T lymphocytes and contribute to the progression of disease.

Increased concentrations of soluble HLA class I and class II molecules (sHLA-I and sHLA-II) have been observed in infectious, inflammatory, and autoimmune diseases. Because autoimmune mechanisms are considered to play a role in the pathogenesis of multiple sclerosis (MS), we decided to dose sHLA-I and sHLA-II in serum and cerebrospinal fluid (CSF) of MS patients comparing their concentrations with those observed in serum and CSF of patients with other neurologic diseases (OND) without evidence of neuroradiologic involvement of central nervous system (CNS) and in serum of healthy donors. The serum concentrations of sHLA-I were higher in both MS and OND patients than in healthy donors (P < 0.05) whereas sHLA-II serum concentrations were lower in MS patients than in both OND patients and healthy donors (P < 0.01). Detectable amounts of sHLA-II were observed in the CSF of 45% of MS patients and in CSF of only 6% of OND patients (P < 0.001). In MS patients a significant correlation between sHLA-I serum and CSF concentrations was observed (P < 0.01), whereas sHLA-II serum and CSF levels did not correlate. In conclusion, alterations of sHLA-I and sHLA-II serum and CSF concentrations are present in MS patients and could be involved in the induction of enhanced susceptibility to develop MS or in MS pathogenesis.

The study was conceived to evaluate if S-adenosil-L-methionine, a substance commonly used in the treatment of cholestasis in patients with cirrhosis and chronic hepatitis, exerts any immunological effect and of it is able to counterbalance bile acid-mediated immunosuppression. Proliferation and interleukin 2 and interferon-gamma secretion of human lymphocytes, collected from healthy subjects and exposed to mitogenic stimuli (phytohemagglutinin, pokeweed and anti-CD3 monoclonal antibodies), were analysed in the basal condition or after exposure to S-adenosil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and interferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated interleukin 2 secretion. S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2 secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon all stimuli tested. Moreover, S-adenosil-L-methionine counteracted chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion. The results of our study confirm the immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion.

A review was made of the medical records of 26 patients with uterine myomas during pregnancy between 1983 and 1992 among 12,965 deliveries. Thirteen patients underwent myomectomies before pregnancy. In three patients myomectomy was performed during pregnancy between the 12th and the 19th week of pregnancy. In ten patients myomectomy was performed during cesarean section delivery to prevent necrobiosis. Myomectomy should remain exceptional during pregnancy and it must be performed only in selected cases but is frequently used towards the end of a cesarean section. Indications for hysterectomy, on the other hand, remain limited.

Background: No estimate exists of the incidence of pelvic inflammatory disease (PID) after the occurrence of a recent bout of sexually transmitted disease (STD)., Methods: We used a computerized data file of prescriptions and medical encounters from the Fallon Community Health Plan to estimate the incidence rate of pelvic inflammatory disease (PID) among women with a recently treated episode of gonorrhea or chlamydia (STD). First we identified women with presumed gonorrhea or chlamydia on the basis of a combination of diagnostic codes for cervicitis, vulvovaginitis or Bartholin's abscess, and a computer record of a prescription for doxycycline. We then followed these women to estimate the incidence rate of PID after their treatment for gonorrhea or chlamydia. We estimated the number of cases of pelvic inflammatory disease in this cohort by selecting all women with an International Classification of Diseases (ICD) code of 614.9 entered for either an outpatient or inpatient diagnosis., Results: We estimated the overall risk of PID to be about 9% during the 1-year period following treatment for gonorrhea or chlamydia, with a steep rise in risk coming within the first 45 days., Conclusion: The risk of PID in the year after an episode of treated STD is high, but the highest period of risk is in the first few weeks. The shape of the risk curve indicates that some PID cases may result from treatment-resistant infections, or possibly from untreated reinfections.

Corticosteroids are among the most used anti-inflammatory and immunosuppressive drugs. The most recent reports have shown that the corticosteroids: A) modulate the lymphocyte recirculation and induce a lymphocyte depletion mainly regarding to the CD4 cells. B) Inhibit several lymphocyte activities, as well as their capacity to secrete cytokines and their clonal expansion under activating conditions. C) Induce apoptosis in primed T cells. D) Modulate the synthesis and activity of nuclear factors AP1 and NFkB. Moreover several data suggest that the molecular manipulations of cortisol, performed with the aim of improving its therapeutic efficiency, might change its capacity to bind the cytoplasmic receptor and/or generate CTS/CTS-R compounds that have different capacity to migrate through the nuclear membrane and/or to activate the nuclear responsive elements inducing different biologic responses.

Objective: To demonstrate the involvement of T lymphocytes reactive to autoantigens in the pathogenesis of autoimmune diseases and to analyse their clinical relevance., Methods: The frequency of T cell clones reactive to double strand DNA (dsDNA), Nucleohistone (NH) complex and Dnase I was calculated for the peripheral blood mononuclear cells (PBMC) of 15 SLE patients and 9 healthy subjects by proliferation assay., Results: DsDNA- and NH-specific T cell clones were found in the majority of the patients analysed (frequency ranging from 2 to 50 clones/10(7) PBMC), while their absence or very low frequency (2 clones/10(7) PBMC) was observed in the control PBMC. Their frequency significantly correlated with decreased serum concentrations of C3 and C4 and with the systemic lupus erythematosus disease activity index (P = 0.03). A very low frequency of Dnase I-reactive T cell clones was observed in both SLE and healthy subjects., Conclusion: Our results suggest that dsDNA- and NH-reactive T lymphocytes may be involved in the pathogenesis of SLE and that their quantification in the peripheral blood of patients could be a useful tool to follow the clinical course of the disease.

Glucocorticoid hormones (GCH) regulate, through the apoptotic process, the negative selection of immature T cells in the thymus. Because apoptosis seems to occur also in the maintenance of peripheral tolerance, we have investigated whether GCH may induce apoptosis in human mature lymphocytes. Peripheral blood lymphocytes (PBL) or peripheral CD4(+) and CD8(+) T cell subsets were cultured in the presence of phytohaemaglutinin (PHA) or PHA and prednisone (PDN) at 10(-3)-10(-12)M concentrations for 72, 96 and 120h. Cell cycle and membrane antigen expression were evaluated by flow cytometry and DNA degradation was detected by agarose gel electrophoresis. PDN blocks PBL growth in the G1 phase of cell cycle and inhibits both IL-2 receptor (IL-2R) expression and IL-2 secretion. Apoptosis is clearly increased by PDN in PHA-activated human PBL, and the apoptotic effect of PDN is stronger on CD8(+) than on CD4(+) T lymphocytes. All these effects are dose- and time-dependent. The addition of exogenous IL-2 did not rescue lymphocytes from PDN-increased apoptosis. These results show that PDN increases apoptosis in mature activated human peripheral blood lymphocytes, suggesting a possible role of GCH in the maintenance of immune tolerance at post-thymic level.

Advances in vascular radiology techniques for superselective transfemoral arterial infusion prompted us to evaluate the effects of high-dose rapid regional carboplatin infusion for patients with advanced head and neck squamous cell carcinomas. Twenty untreated patients received three infusions of carboplatin (300-350 mg/m2) every 2 weeks with this method. All the infusions were performed without any complication. Treatment was well tolerated, with moderate (Grade 1-3 WHO) local toxicity (stomatitis, dermatitis and alopecia) and minimal (Grade 1-2 WHO) myelosuppression. The total response index (complete response plus partial response) was 94% for primary tumors and 50% for neck metastases. Neoadjuvant chemotherapy employing superselective rapid infusion of high-dose carboplatin is a feasible, relatively nontoxic, effective technique and may have important applications in multimodality therapy of untreated patients with advanced head and neck cancer.

In the present study T lymphocytes isolated from a metastatic lymph node (T-LNL) of a melanoma patient have been cloned. In the attempt to verify whether T-LNL may acquire in vitro functional activities in the absence of tumour-associated antigens, they were cloned utilizing allogenic lymphocytes as feeder cells. Nineteen clones generated from T-LNL proved to be CD4+ and, among these, five were able to kill autologous and allogeneic human melanoma cells in HLA-class-II-restricted way. On the basis of their cytokine production, these CD4+ cytolytic T-LNL clones were shown to belong to the Th0 subset and three of them expressed the V beta 17 chain of the T cell receptor. These results suggest the presence of melanoma-specific but functionally inactive lymphocytes with T cell receptor oligoclonality in the lymph node environment. These specific T cells may acquire in vitro the capacity to kill autologous and allogeneic tumours without any induction by autologous melanoma cells.

HLA class I and class II antigens circulate in serum as soluble molecules. Increased concentrations of soluble HLA class I molecules have been demonstrated in viral diseases, in rejection episodes following organ transplantation and in graft versus host disease. To explore the possibility of a variation of the serum concentrations of soluble HLA class II molecules in the same pathologic conditions we developed a double determinant immune assay that detects whole soluble HLA-DR molecules (sHLA-DR). The mean level of sHLA-DR antigens in sera from 23 healthy individuals was 0.64 +/- 0.72 microgram/ml. Elevated serum concentrations of sHLA-DR molecules were detected in sera from HIV infected patients in CDC2/3 and in CDC4 C1 stages (2.0 +/- 1.7 micrograms/ml and 4.6 +/- 1.7 micrograms/ml, respectively), in sera from patients affected by acute rejection after liver transplantation (5.3 +/- 3.7 micrograms/ml) and in sera from patients affected by severe acute graft versus host disease following bone marrow transplantation (8.8 +/- 3.1 micrograms/ml). The increase of sHLA-DR molecules in these sera significantly correlated with the elevation of soluble HLA class I antigens (P = 0.0004). The reported data suggest that both soluble HLA class I and class II molecules serum levels increase during viral infections and strong immune reactions and could suggest the involvement of these molecules in immunoregulation.

The relative potency of interferon alpha (IFN alpha), interferon beta (IFN beta), and interferon gamma (IFN gamma) in inducing the expression of HLA class I antigens, as well as their capacity to counteract the inhibition induced by glucocorticoid hormones on HLA class I antigen expression, were analysed in the human melanoma cell line M14, both at membrane and at mRNA level. The data obtained indicate that (a) IFN enhance with different potency (IFN gamma > IFN beta > IFN alpha) the expression of HLA class I antigens in M14 cells, (b) prednisone inhibits HLA class I antigen expression, (c) glucocorticoid hormones, when associated with IFN alpha or IFN gamma, inhibit the HLA class I enhancement induced by IFN alone, and, finally, (c) the association between 1 microM prednisone or 1 microM deflazacort and IFN beta seems to potentiate the enhancing capacity of IFN on the expression of HLA class I molecules at the mRNA level. These findings, if confirmed, might indicate that IFN and glucocorticoid hormones are not mutually exclusive in the management of human melanoma.

Objective: To describe the monitoring of liver function for patients using nonsteroidal anti-inflammatory drugs (NSAIDs), we reviewed the patterns of liver function testing in a medium-sized health maintenance organization., Methods: We examined the interval between start of therapy and first performance of a liver function test during courses of therapy of the NSAIDs diclofenac sodium, naproxen and naproxen sodium, and piroxicam. For comparison, we also studied courses of lovastatin as a "positive control," in which the anticipated frequency of liver function testing was high., Results: The frequency of liver function tests in patients using NSAIDs was generally low, although testing was more common in patients who used diclofenac. The probability of liver function testing was higher for patients treated in recent calendar years, for patients treated by rheumatologists, for patients who previously used NSAIDs, and for patients who had undergone a liver function test sometime in the 6 months preceding the onset of therapy., Conclusion: Physicians ordered liver function tests less frequently than recommended, but the observed testing patterns appear rational in light of the very low reported frequency of serious hepatic disease in large, monitored populations of patients using NSAIDs.

Analysis of (sHLA-I) antigens in a large number of HIV-positive subjects found a significant increase of their level, but did not detect any change in their molecular profile. Monitoring at yearly intervals for four years of the sHLA-I antigen level in 14 HIV-positive subjects with a normal sHLA-I antigen level at study entry showed a significant correlation between progressive increase of sHLA-I antigen level and disease progression. Furthermore, a Kaplan-Meier plot of the frequency of development of AIDS in 34 patients whose cases were followed for 7 years showed that sHLA-I antigen level is a strong predictor of progression to AIDS. Its predictive value is comparable to that of serum beta 2-mu level, greater than that of serum neopterin, and lower than that of CD4+ T-cell percentage. The predictive value of sHLA-I antigen level in combination with serum beta 2-mu level, neopterin level, or CD4+ T-cell percentage is greater than that of each individual variable. These results suggest that measurement of the sHLA-I antigen level may provide useful prognostic information in HIV-positive subjects.

In order to determine the possible interactions between histocompatibility leukocyte antigen (HLA) -class I antigens and beta-adrenergic receptors, we evaluated the effects of anti-HLA class I monoclonal antibodies on beta-adrenoceptor-mediated intracellular production of cAMP in human mononuclear leukocytes. Moreover, we studied whether anti-HLA class I monoclonal antibodies inhibit the binding of a specific radioligand to the beta-adrenoceptors, and, conversely, whether both isoproterenol and propranolol interfere with the binding (evaluated by a cytofluorometric assay) of the anti-HLA class I monoclonal antibodies to the cell membrane. Our results showed that anti-HLA class I monoclonal antibodies induced a significant beta-adrenergic-dependent increase in intracellular cAMP whereas anti-HLA class II and antimelanoma monoclonal antibodies were ineffective. Moreover anti-HLA class I monoclonal antibodies inhibited, in part, the specific binding of a beta-adrenergic radioligand, although they did not induce the internalization of the beta-adrenoceptors. On the other hand, both isoproterenol and propranolol induced a significant decrease in the peripheral blood mononuclear cell expression of HLA-class I molecules. Our data suggest that important interactions between major histocompatibility complex gene products and the beta-adrenergic receptors may occur in human cells.

This report describes a 6-year-old girl with pre-B ALL who developed systemic aspergillosis following BMT. She was successfully treated with a combination of amphotericin B, itraconazole and surgery. This report emphasizes the importance of surgical resection in the management of disseminated aspergillosis.

Different glucocorticoid preparations modify the immune reaction in different ways. In this paper, the therapeutic efficacy of two glucocorticoids, deflazacort (DFZ) and prednisone (PDN), are discussed in relation to a group of 30 patients with systemic lupus erythematosus (n = 12) or rheumatoid arthritis (n = 18). The disease sub-groups were divided into two arms, one of which was treated with DFZ and one with PDN in a double-blind protocol. The results of this study indicate that DFZ and PDN induced a clinical remission within 1 month which was maintained until the 6th month. Nevertheless, certain immunological modifications, including a significant reduction of the circulating T lymphocyte level and of the CD4/CD8 ratio, which was between 1 and 1,5 during the DFC treatment and between 1 and 2 during the PDN treatment, are more pronounced and more stable with DFZ than with PDN. Moreover, DFZ has a smaller effect on calcium and glucose metabolism than PDN since the serum glucose and calcium level of patients treated with PDN increased respectively from 90 up to 130 mg/dl and from 9,5 to 11,5 mg/dl whereas those of patients treated with DFC remained within the normal range. These findings indicate that DFZ may have advantages over PDN in the treatment of immune-mediated diseases.

The effects of the glucocorticoid hormones prednisone (PDN) and deflazacort (DFC) on MHC gene products membrane expression and mRNA level were evaluated on peripheral blood lymphocytes and on the melanoma M14 cell line. The modulatory effect of the association of PDN and DFC with interferon-γ was also evaluated. PDN and DFC inhibited MHC gene expression in lymphocytes and M14 cells both on the cell membrane and at the mRNA level. Interferon-γ was able to counteract this inhibitory effect. These results may contribute to clarify the role played by glucocorticoid hormones in the modulation of immune responses., (© 1992 S. Karger AG, Basel.)

In the present paper we analyze the role of major histocompatibility gene products, the human leukocyte antigens, in the pathophysiology of the acquired immunodeficiency syndrome. No association has been found between human leukocyte antigen (HLA) frequencies and human immunodeficiency virus type 1 (HIV 1) infection, whereas significant associations have been reported in some populations between some HLA haplotypes and the appearance of either opportunistic infections or secondary cancers. With regard to the human leukocyte class I antigens, their role as restriction elements in presenting HIV 1 to virus-specific cytotoxic T lymphocytes seems to be established. An increase in the serum levels of their soluble forms that correlate with disease stage has also been demonstrated. These circulating molecules could interfere with the immune response to HIV 1 and could contribute to the development of the immunodeficiency. Antigenic similarities have been detected between human leukocyte class II antigens and HIV 1 envelope proteins. These homologies could explain both the presence in some HIV-positive sera of anti-HLA class II antibodies that mediate the lysis of CD4(+)-HLA class II+ T cells and the false-positive reaction of some HIV-negative sera, which contain anti-HLA class II antibodies, in tests for HIV 1 antibodies. Reduced levels of some complement factors (the human leukocyte class III antigens) have been detected in HIV-infected subjects. These defects could play a role in the progression of the disease and affect both the clearance of HIV 1 and complement-mediated antibody responses. The data reported in this review suggest that HLA antigens may be involved in several steps of the immune deficiency of HIV-infected subjects and thus contribute to the pathophysiology of acquired immunodeficiency syndrome.

A simple sandwich ELISA method has been developed for the quantification of soluble HLA class I antigens (s-HLA) in human serum. The assay utilizes the monoclonal antibody Q6/64, directed to a monomorphic determinant of the HLA alpha-chain, to capture the antigen and the biotinylated NAMB1 monoclonal antibody, directed to beta 2-microglobulin, as the detection antibody. The extract of the LG-2 lymphoid cell line and pooled sera from 100 healthy subjects are utilized as standards. The arbitrary value of 100 s-HLA Relative Units/mL (RU/mL) is given to the 1:20 dilution of pooled human sera whose optical density value corresponds to the one of the extract of 1 x 10(6) LG-2 cells (6.25 micrograms/mL protein concentration). The assay is easy to perform, specific, reproducible (intra- and inter-assay variations ranging from 3.2% to 8.87%), sensitive (detection limit of 6 RU/mL), and needs a small amount of serum (0.1 mL). The mean serum levels of s-HLA found in 100 healthy normal subjects are 41.9 +/- 13.4 RU/mL. The potential uses of the method are discussed.