Self-reported health and comfort in 'modern' office buildings: first results from the European OFFICAIR study.

In the European research project OFFICAIR, a procedure was developed to determine associations between characteristics of European offices and health and comfort of office workers, through a checklist and a self-administered questionnaire including environmental, physiological, psychological, and social aspects. This procedure was applied in 167 office buildings in eight European countries (Portugal, Spain, Italy, Greece, France, Hungary, the Netherlands, and Finland) during the winter of 2011-2012. About 26 735 survey invitation e-mails were sent, and 7441 office workers were included in the survey. Among respondents who rated an overall comfort less than 4 (23%), 'noise (other than from building systems)', air 'too dry', and temperature 'too variable' were the main complaints selected. An increase of perceived control over indoor climate was positively associated with the perceived indoor environment quality. Almost one-third of office workers suffered from dry eyes and headache in the last 4 weeks. Physical building characteristics were associated with occupants' overall satisfaction (acoustical solutions, mold growth, complaints procedure, cleaning activities) and health (number of occupants, lack of operable windows, presence of carpet and cleaning activities). OFFICAIR project provides a useful database to identify stressors related to indoor environmental quality and office worker's health.

TRAIL death receptors DR4 and DR5 mediate cerebral microvascular endothelial cell apoptosis induced by oligomeric Alzheimer's Aß.

Vascular deposition of amyloid-ß (Aß) in sporadic and familial Alzheimer's disease, through poorly understood molecular mechanisms, leads to focal ischemia, alterations in cerebral blood flow, and cerebral micro-/macro-hemorrhages, significantly contributing to cognitive impairment. Here, we show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors DR4 and DR5 specifically mediate oligomeric Aß induction of extrinsic apoptotic pathways in human microvascular cerebral endothelial cells with activation of both caspase-8 and caspase-9. The caspase-8 inhibitor cellular FLICE-like inhibitory protein (cFLIP) is downregulated, and mitochondrial paths are engaged through BH3-interacting domain death agonist (Bid) cleavage. Upregulation of DR4 and DR5 and colocalization with Aß at the cell membrane suggests their involvement as initiators of the apoptotic machinery. Direct binding assays using receptor chimeras confirm the specific interaction of oligomeric Aß with DR4 and DR5 whereas apoptosis protection achieved through RNA silencing of both receptors highlights their active role in downstream apoptotic pathways unveiling new targets for therapeutic intervention.

Frecuencia de neumococos del serotipo 19A en otitis media aguda en niños inmunocompetentes antes de la aplicación masiva de la vacuna conjugada / Incidence of 19A pneumococci in acute otitis media in immunocompetent children before the massive administration of the conjugated vaccine

La aplicación de la vacuna PCV7 en algunos países ha determinado un aumento significativo de neumococos del serotipo 19A y este hecho ha llevado a una atenuación del impacto inicial logrado en términos de prevención de enfermedades neumocócicas invasivas. Los objetivos de este trabajo fueron: (a) describir la frecuencia de los neumococos 19A, antes de la vacunación antineumocócica masiva, en niños con OMA desde la óptica parcial de un solo hospital de la ciudad de Buenos Aires, (b) estudiar su vinculación a casos de recurrencias y (c) su sensibilidad a los antimicrobianos. Se aislaron 133 neumococos, 126 de los cuales resultaron viables para poder realizar su identificación a nivel de tipo y los estudios correspondientes de sensibilidad a los antibióticos. Los serotipos más prevalentes fueron el 14 (14,3%) y el 19A (11,9%). Ocho de los 15 aislados de S. pneumoniae 19A presentaron sensibilidad disminuida a la penicilina, lo que representó el 22,2% de los neumococos no sensibles provenientes de OMA. El serotipo 19A estuvo involucrado en 3 de los 12 casos de recurrencias por S. pneumoniae. Probablemente la nueva vacuna 13-valente, la única conjugada que contiene antígenos contra el neumococo 19A, pueda impedir su incremento tanto en OMA como en enfermedades invasivas.

In several countries administration of PCV7vaccine has cau-sed a significant increase in 19A serotype pneumococci.This effect has diminished the initial impact on invasive pneumococcal infection prevention. The aims of the present study were: (a) to describe the incidence of 19A pneumococci in children with acute otitis media (AOM), beforethe massive administration of pneumococcal vaccines, fromthe scope of a single pediatric hospital in the city of Buenos Aires, (b) to study their relation to recurrences, and (c) their antimicrobial susceptibility. One hundred and thirty-three pneumococci were isolated from children with AOM; 126 of these were viable to further identify pneumococcal serotypes and determine antimicrobial susceptibility. The most prevalent serotypes were 14 (14.3%) and 19A (11.9%). Eightout of the 15 19A serotype pneumococcal isolates showed diminished susceptibility to penicillin, accounting for 22.2% of non-susceptible pneumococci from AOM. Serotype 19A was involved in 3 out of 12 cases of recurrent AOM due to S. pneumoniae. The new 13-valent vaccine, containing antibodies against 19A pneumococci, may prevent its increasing incidence rate both in AOM and in other invasive infections.

[Assessment of comfort and health status of Call Center's workers]. / La valutazione del comfort e dello stato di salute in lavoratori di un Call Center.

BACKGROUND: Call Centers are workplaces in which there are a lot of occupational health hazards. METHODS: The aim of the study was to investigate Call Center operators' health status, using: "Ambiente/Salute" questionnaire, VHI questionnaire, health surveillance data analysis. RESULTS: "Negative" Microclimate rating: 68%; "negative" noise rating: 51%. "Negative" eye symptoms rating: 30%; "negative" postural disorders rating: 21%. "Negative" VHI value (over the limit of 30): 6%. CONCLUSIONS: It's necessary to develop and validate an appropriate health surveillance protocol

Differential activation of mitochondrial apoptotic pathways by vasculotropic amyloid-beta variants in cells composing the cerebral vessel walls.

Cerebral amyloid angiopathy (CAA) is an age-associated condition and a common finding in Alzheimer's disease in which amyloid-beta (Abeta) vascular deposits are featured in >80% of the cases. Familial Abeta variants bearing substitutions at positions 21-23 are primarily associated with CAA, although they manifest with strikingly different clinical phenotypes: cerebral hemorrhage or dementia. The recently reported Piedmont L34V Abeta mutant, located outside the hot spot 21-23, shows a similar hemorrhagic phenotype, albeit less aggressive than the widely studied Dutch E22Q variant. We monitored the apoptotic events occurring after stimulation of human brain microvascular endothelial and smooth muscle cells with nonfibrillar structures of both variants and wild-type Abeta40. Induction of analogous caspase-mediated mitochondrial pathways was elicited by all peptides, although within different time frames and intensity. Activated pathways were susceptible to pharmacological modulation either through direct inhibition of mitochondrial cytochrome c release or by the action of pan- and pathway-specific caspase inhibitors, giving a clear indication of the independent or synergistic engagement of both extrinsic and intrinsic mechanisms. Structural analyses of the Abeta peptides showed that apoptosis preceded fibril formation, correlating with the presence of oligomers and/or protofibrils. The data support the notion that rare genetic mutations constitute unique paradigms to understand the molecular pathogenesis of CAA.

Pertussis epidemiology in Argentina: trends over 2004-2007.

OBJECTIVES: Pertussis continues causing significant morbidity and mortality worldwide. Although its epidemiology has been studied in many developed countries, the current pertussis situation in South America is scarcely known. This review summarizes the most important recent data concerning pertussis in a country of South America, Argentina. METHODS: CDC criteria were used for pertussis diagnosis. Proportion of pertussis cases by age, immunization status, and immunization coverage rate evaluated at the Argentinean National Pertussis Reference Centers was reported. Bordetella pertussis isolates were characterized and compared with vaccine strains. RESULTS: From 2002 to nowadays, a steady increase of pertussis cases was observed. Most of these cases correspond to patients younger than six months old that received less than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Argentina, several explanations have been proposed. Among them, the inability of current vaccines to induce long-lasting immunity is the most widely accepted as a cause of pertussis resurgence. Furthermore, antigenic divergence between local clinical isolates and vaccine strains may have aggravated the effect of waning immunity. CONCLUSIONS: Pertussis is an important problem for public health in Argentina. Divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.

Tauroursodeoxycholic acid prevents E22Q Alzheimer's Abeta toxicity in human cerebral endothelial cells.

The vasculotropic E22Q mutant of the amyloid-beta (Abeta) peptide is associated with hereditary cerebral hemorrhage with amyloidosis Dutch type. The cellular mechanism(s) of toxicity and nature of the AbetaE22Q toxic assemblies are not completely understood. Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells by AbetaE22Q and wild-type Abeta revealed that only AbetaE22Q triggered the Bax mitochondrial pathway of apoptosis. AbetaE22Q neither matched the fast oligomerization kinetics of Abeta42 nor reached its predominant beta-sheet structure, achieving a modest degree of oligomerization with a secondary structure that remained a mixture of beta and random conformations. The endogenous molecule tauroursodeoxycholic acid (TUDCA) was a strong modulator of AbetaE22Q-triggered apoptosis but did not significantly change the secondary structures and fibrillogenic propensities of Abeta peptides. These data dissociate the pro-apoptotic properties of Abeta peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity.

High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo.

High mobility group proteins are chromatin binding factors with key roles in maintenance of nuclear homeostasis. The evidence indicates that extracellularly released high mobility group box 1 (HMGB1) protein behaves as a cytokine, promoting inflammation and participating to the pathogenesis of several disorders in peripheral organs. In this study, we have investigated the expression levels and relocation dynamics of HMGB1 in neural cells, as well as its neuropathological potential. We report that HMGB1 is released in the culture media of neurons and astrocytes challenged with necrotic but not apoptotic stimuli. Recombinant HMGB1 prompts induction of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-1beta, and tumor necrosis factor alpha, and increases excitotoxic as well as ischemic neuronal death in vitro. Dexamethasone reduces HMGB1 dependent immune glia activation, having no effect on the protein's neurotoxic effects. HMGB1 is expressed in the nucleus of neurons and astrocytes of the mouse brain, and promptly (1 h) translocates into the cytoplasm of neurons within the ischemic brain. Brain microinjection of HMGB1 increases the transcript levels of pro-inflammatory mediators and sensitizes the tissue to the ischemic injury. Together, data underscore the neuropathological role of nuclear HMGB1, and point to the protein as a mediator of post-ischemic brain damage.

Treatment of benign nodular goitre with mildly suppressive doses of L-thyroxine: effects on bone mineral density and on nodule size.

OBJECTIVES: To evaluate (i) the demineralizing effect of L-thyroxine (LT4) therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in patients with benign nodular goitre; (ii) the efficacy of treatment on nodule size. DESIGN: Cross-sectional study comparing euthyroid women with nodular goitre treated with LT4 for > or = 2 years (52 +/- 32 months, range 24-138, median 42) and a matched group with untreated goitre. SUBJECTS: A total of 89 female outpatients (53.3 +/- 9 years; 36 pre- and 53 postmenopausal), 43 treated and 46 untreated. MAIN OUTCOME MEASURES: Bone mineralization was measured with total body and regional mineralometry [dual energy X-ray absorptiometry (DEXA)], and indirectly evaluated with biochemical parameters (alkaline phosphatase, osteocalcin). Efficacy of LT4 therapy was assessed by measuring the nodule size during ultrasonography. The adequacy of the treatment was evaluated on the basis of serum TSH levels. RESULTS: No significant differences were found at DEXA for total body and regional mineralization (P > 0.05 for all comparisons) in treated and untreated patients, both in pre- and postmenopausal states. Evaluation of the nodule size during the ultrasound scan showed a reduction of > or = 30% in 11 of 43 treated patients (26%) versus none of the untreated, an unchanged size in 29 treated patients (67%) versus 18 untreated, an increase of nodules and/or new nodule development in three treated patients (7%) versus 28 untreated (61%). CONCLUSIONS: L-thyroxine (LT4) treatment at doses slightly suppressing TSH does not significantly affect bone mineralization, nor does it represent a risk factor for osteoporosis, even in postmenopausal patients. The efficacy of this therapeutic schedule on goitre size is comparable with the effects previously reported with suppressive doses.

Functional analysis of HIV-specific cytotoxic T lymphocytes in antiviral-treated- and-naive patients: a preliminary report.

HIV-specific CTL functions were analyzed in HIV-infected individuals who did or did not receive antiretroviral therapy (ART). Results showed that gp 160 (env)-stimulated perforin- and granzyme-expressing CTL, as well as perforin and granzyme-specific mRNA, were reduced in treated patients whereas TNFalpha was increased in ART-treated compared to naive individuals. Reduction of perforin and granzyme-expressing cells was not secondary to impaired IFNgamma production. A defect of CTL is observed in ART-treated individuals; this defect is not dependent on impaired Th cell function. These results reinforce the need for immunomodulants to successfully approach therapy of HIV infection.

Single-cell analysis of cytokine production shows different immune profiles in multiple sclerosis patients with active or quiescent disease.

Peripheral blood mononuclear cells of multiple sclerosis (MS) patients were stimulated with myelin basic protein (MBP) together with anti-CD28 monoclonal antibody and staphylococcal enterotoxin B to optimize cytokine production by antigen-specific cells. Type 1 (IL-2, IL-12, IFNgamma) and pro-inflammatory (TNFalpha, IL-1beta, IL-6) cytokines were augmented in CD4+, CD8+, and CD14+ cells of acute MS patients and of patients undergoing disease reactivation. These cytokines were reduced in IFNbeta-treated and in stable MS patients; type 2 cytokines (IL-4, IL-10) were increased in these patients. Similar immune profiles are seen in MS patients in whom remission is naturally or pharmacologically (IFNbeta) achieved. Cytokine alterations are particularly evident in CD14+ cells, underlying their critical role in the modulation of the immune response.

Evaluation of immune activation in HIV-infected and uninfected African individuals by single-cell analysis of cytokine production.

Immune activation has been observed in HIV-infected and uninfected Africans, among whom it is thought to modify interaction between the immune system and HIV. To characterize this phenomenon accurately, in-depth immunologic analyses were performed in a rural African population. Freshly drawn peripheral blood mononuclear cells (PBMCs) of HIV-infected African (from Gulu, Uganda) and Italian antiviral-naive patients and those of uninfected Ugandan and Italian study subjects were analyzed. Individuals were matched for age and sex and determined to be free from parasitic infections. Intracellular cytokines were measured in mitogen (M)- and gp160 peptides + staphylococcal enterotoxin B and alpha CD28 (env)-stimulated T lymphocytes. Interferon (IFN)-gamma-producing CD8(+) T cells were quantified in an enzyme-linked immunosorbent assay. Results showed that M-stimulated production of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha increases in CD4(+) and CD8(+) cells of African infected patients and uninfected study subject; and that env-stimulated IL-10 and TNF-alpha production is increased in CD8(+) T lymphocytes of African HIV-infected patients. M- and env-stimulated IFN-gamma-producing CD8(+) T cells were reduced in African participants and not increased by preincubation with alpha IL-10 monoclonal antibody. This is the first set of data that has reported immune activation in rural Africa by single-cell analysis of cytokine production. These results help in defining the immunologic background to be considered in the design of therapeutic and vaccine-based approaches to HIV infection in an African setting.

Human herpesvirus 8 DNA in the skin and blood of patients with Mediterranean Kaposi's sarcoma: clinical correlations.

BACKGROUND: Kaposi's sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi's sarcoma by confirmational display analysis and polymerase chain reaction. OBJECTIVE: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi's sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. METHODS: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi's sarcoma. RESULTS: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi's sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV. CONCLUSION: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi's sarcoma.

In vitro immunomodulatory properties of tucaresol in HIV infection.

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.

T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

Photopheresis in cutaneous T-cell lymphoma: five-year experience.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) includes several lymphoproliferative disorders involving mature T-lymphocyte proliferation initially confined to the cutis. These affections, after variable periods, may progress to the blood, limph nodes and visceral organs. Mycosis fungoides (MF) is the most frequent form of CTCL and has an indolent clinical course. The therapy of CTCL depends on the stage of the disease and the patient's general conditions. For advanced cases it includes chemotherapy, retinoids, and interferon-alpha. Since 1987 extracorporeal photochemotherapy (ECP), a novel immunomodulatory approach based on apheresis and photoirradiation of leukocytes, has been successfully introduced for the treatment of advanced CTCL. It can prolong survival of patients with erythrodermic CTCL without significant side effects. OBJECTIVE: To review our five-year experience with ECP in CTCL. METHODS: Since June 1994, 33 CTCL patients have been recruited for ECP, using two different regimens: two procedures on two consecutive days at four-week intervals for six months, or at two-week intervals for three months with progressive tapering in the second three-month period for the more severe forms. Six patients received ECP with IFN-alpha. ECP was done using the photopheresis UVAR system and UVAR XTS (Therakos, West Chester, Pa) and always with 8-MOP liquid formulation injected directly into the buffy coat bag. Lymphocytes in peripheral blood were immunophenotypically characterized for each patient and every ECP session. RESULTS: All patients tolerated ECP well, without significant side effects. Thirty patients are clinically evaluable (at least three ECP cycles). A favourable clinical response was obtained in 80.9% (16/21) of MF patients (complete response 33%, partial response 47.6%) and in 66% (6/9) of patients in the Sézary's syndrome phase (complete response 33.3%, partial response 33.3%). Five of the six patients given IFN-alpha as adjunctive therapy had a PR and one a CR. Four patients are in CR without therapy at follow-ups of 46, 20, 10 and 8 months. There have been no changes in the peripheral lymphocyte immunophenotype during the follow-up. In 19/30 patients the CD95 antigen, correlated with cellular apoptosis, was expressed and was frequently associated with a good clinical response. CONCLUSIONS: In our experience ECP achieved favourable clinical responses in 73% of patients, in monotherapy or in combination with IFN-alpha, without significant side effects.

Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders.

BACKGROUND: The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or Mediterranean, endemic or African, posttransplant, and epidemic or acquired immunodeficiency syndrome-associated KS. In its classic form KS mainly affects elderly people and often has a long and indolent course that occasionally allows other malignancies to appear. Previous studies of the possible association between human immunodeficiency virus (HIV) negative KS and lymphoproliferative disorders (LDs) have produced discordant results. METHODS: To verify a possibly significant association between HIV negative KS and LDs, data relating to 250 evaluable Italian patients with HIV negative KS were evaluated retrospectively. RESULTS: Of the 250 KS patients, only 6 (2.4%) were found to have had an LD: 2 with Hodgkin lymphoma, 1 with non-Hodgkin lymphoma, 1 with cutaneous T-cell lymphoma, 1 with acute promyelocytic leukemia, and 1 with B-chronic lymphocytic leukemia. CONCLUSIONS: No significant association was found between HIV negative KS and LDs in the patient population in the current study. The authors believe that age, LD, or therapy-related immunodepression played a role in the cases in which KS appeared after the LD by determining the passing to the lytic phase of the herpes-virus HHV8 already present in anatomic sites of latency/persistence.

Regional effects of cholecystokinin octapeptide on colonic phasic and tonic motility in healthy humans.

The aim of this study was to assess in nine healthy subjects the effects of CCK octapeptide (CCK-8) on colonic tonic activity, measured by a barostat, and phasic activity, measured by manometry. On 2 consecutive days, recordings were performed in the unprepared proximal and distal colons during intravenous infusion of saline and CCK-8 at 5, 20, and 40 ng. kg-1. h-1. In the proximal colon CCK-8 induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic relaxation with an increase in barostat bag volume to 156 +/- 25 and 157 +/- 19% of basal (P < 0.01) and a decrease in phasic activity to 72 +/- 7 and 76 +/- 7% of basal (P < 0.01). In the distal colon, CCK-8 induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic relaxation (increase in intrabag volume to 133 +/- 12 and 149 +/- 15%, respectively; P < 0.01), whereas phasic activity increased (128 +/- 8 and 132 +/- 6%, respectively; P < 0.01). Effects of CCK-8 on tonic and phasic activities are different according to the colonic segment. Because meals induce colonic tonic contraction, our results suggest that CCK, as a hormone, is not an important mediator of the response of the colon to feeding in humans.

Vinorelbine therapy for Kaposi's sarcoma in a kidney transplant patient.

We report the case of a patient with Kaposi's sarcoma after kidney transplantation. Despite the discontinuation of azathioprine and a reduction in the cyclosporin dosage, the disease continued to evolve, and antineoplastic treatment became necessary. After 14 cycles of vinorelbine chemotherapy, there was a 75% regression of the initial lesions, despite the continuation of cyclosporin A.