In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas.

We have analyzed the presence of immature and mature dendritic cells (DCs) within adenocarcinoma of the breast using immunohistochemistry. Immature DCs were defined by expression of CD1a-, Langerin-, and intracellular major histocompatibility complex class II-rich vesicles. Mature DCs were defined by expression of CD83 and DC-Lamp. Breast carcinoma cells were defined by morphology and/or cytokeratin expression. We demonstrate two levels of heterogeneity of DCs infiltrating breast carcinoma tissue: (a) immature CD1a(+) DCs, mostly of the Langerhans cell type (Langerin(+)), were retained within the tumor bed in 32/32 samples and (b) mature DCs, CD83(+)DC-Lamp(+), present in 20/32 samples, are confined to peritumoral areas. The high numbers of immature DCs found in the tumor may be best explained by high levels of macrophage inflammatory protein 3alpha expression by virtually all tumor cells. Confirming the immature/mature DC compartmentalization pattern, in vitro-generated immature DCs adhere to the tumor cells, whereas mature DCs adhere selectively to peritumoral areas. In some cases, T cells are clustering around the mature DCs in peritumoral areas, thus resembling the DC-T cell clusters of secondary lymphoid organs, which are characteristic of ongoing immune reactions.

Lack of hepatotoxic effects of parenteral ketorolac in the hospital setting.

BACKGROUND: No large controlled studies to date have examined the hepatic safety of parenteral ketorolac, which is used to treat acutely ill hospitalized patients who may be at greatest risk of liver injury. OBJECTIVE: To measure the association between the use of parenteral ketorolac and subsequent liver injury. METHODS: A nonexperimental cohort study conducted in 35 hospitals in the greater Philadelphia, Pa, region examined 10,272 courses of parenteral ketorolac (the exposed group) and 10,247 courses of parenteral opioid (the comparison group). Liver injury was defined by a modified international consensus definition that relied exclusively on liver function tests. Proportional hazards regression was used to calculate the rate ratio and 95% confidence interval for the association between ketorolac exposure and the occurrence of liver injury, controlling for potentially confounding factors, and to explore the possible effects of duration and dose. RESULTS: The incidence of liver injury was 1.0% in the ketorolac group and 1.2% in the opioid group, yielding an unadjusted rate ratio of 0.77 (95% confidence interval, 0.59 1.01). Simultaneously adjusting for multiple potentially confounding factors did not change this result. There was no evidence for a duration-response relationship (P = .96) or a dose-response relationship (P = .23). We were unable to identify any subgroups that were susceptible to possible hepatotoxic effects of parenteral ketorolac. CONCLUSIONS: This study failed to find evidence of a hepatotoxic effect of parenteral ketorolac use in the hospital setting and provides strong evidence against the existence of a clinically meaningful association between exposure to parenteral ketorolac in the hospital setting and liver injury.

Survival of patients with AIDS and cytomegalovirus disease treated with ganciclovir or foscarnet.

We reviewed the hospital charts of 168 patients with AIDS and cytomegalovirus (CMV) disease diagnosed at San Francisco General Hospital between July 1985 and October 1989. One hundred and thirty-three patients had CMV retinitis, 33 had CMV gastrointestinal disease, and two had CMV lung disease. We found a trend towards longer survival from time of CMV disease diagnosis in patients with more recent dates of diagnosis. The median survival of patients diagnosed with CMV disease prior to 30 September 1987 was 4 months, compared with 9 months for patients diagnosed after 30 September 1987 (P = 0.001). The relative hazard of death for patients with CMV retinitis who were initially treated with foscarnet was not significantly reduced compared to those initially treated with ganciclovir. Even after controlling for age at time of CMV diagnosis, time from index AIDS diagnosis, hemoglobin, absolute lymphocyte count, absolute neutrophil count and concurrent zidovudine therapy, the relative hazard for foscarnet-treated patients compared with ganciclovir-treated patients was 1.0 (95% confidence interval, 0.5-1.8).

Pharmacoepidemiology of adverse drug reactions in hospitalized patients with human immunodeficiency virus disease.

To evaluate the incidence, characteristics, and risk factors of adverse drug reactions (ADRs) in patients with human immunodeficiency virus (HIV) disease, we conducted was a prospective observational study of inpatients with HIV disease. The study was conducted in a public teaching hospital affiliated with the University of California, San Francisco. We reviewed daily the hospital records of all eligible inpatients throughout their hospitalization for potential ADRs. Potential ADRs were independently evaluated by two of the authors with regard to the extent of their causal association(s) with implicated drug(s) using a previously validated algorithm. Type (A, augmented; B, bizarre) and severity (mild, moderate, severe) were also evaluated. Among 495 patient admissions involving 390 eligible patients, 173 potential ADRs were identified, of which 118 (68.2%) had a probable or definite causal relationship to the implicated drugs. These probable or definite ADRs occurred among 79 (20%) eligible patients; 82 ADRs (69.5%) were classified as augmented (type A) and 36 (30.5%) were classified as bizarre (type B) reactions. Skin rash was the most frequent (17%) ADR encountered. Of the medications causing ADRs, 70% were antimicrobial drugs. Significant independent risk factors for developing ADRs included advanced stage of HIV disease, intake of a greater number of medications, and longer hospital stay. A high percentage of patients with HIV disease developed ADRs. Skin rash was the single most common kind of ADR. Advanced stage of illness and prolonged drug exposure were the only risk factors for ADRs.

Central venous catheter infections in AIDS patients receiving treatment for cytomegalovirus disease.

Central venous catheters (CVC) are commonly used to deliver daily intravenous medications to patients with AIDS, and CVC-associated bacterial infections have been a cause of substantial morbidity in such patients. Although previous studies have reported rates of CVC-associated infections in AIDS patients, none has compared rates by type of intravenous drug regimen used or by whether CVCs were percutaneously placed or tunneled under the skin. The charts of all AIDS patients diagnosed with cytomegalovirus (CMV) end-organ disease at San Francisco General Hospital between 1985 and 1990 were reviewed for evidence of CVC use and CVC-associated infection. Infection rates and time to infection were analyzed for serious CVC-associated infections (requiring catheter removal or hospitalization for intravenous antibiotic therapy) by type of anti-CMV therapy administered (ganciclovir versus foscarnet) and by type of CVC (tunneled versus percutaneous placement). Fifty-four patients had 72 CVCs in use for 11,622 days of intravenous anti-CMV therapy. There were 36 CVC-associated infections of which 23 were categorized as serious (rate, 0.20/100 catheter days). In patients receiving either ganciclovir or foscarnet therapy, we found no significant difference in serious infection rates or in infection-free survival time (216 vs. 282 days, p = 0.7). However, serious CVC infection-free time was significantly longer in patients with tunneled than with percutaneous CVCs (419 vs. 195 days, p = 0.018). The use of ganciclovir compared to foscarnet in the treatment of AIDS-related CMV disease was not associated with a greater risk of serious catheter-related infection.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of hepatitis C treatment and outcomes at academic, private and Veterans' Affairs treatment centres.

BACKGROUND: Currently, there is a lack of published data examining hepatitis C treatment practices in different care settings. AIM: To provide data describing treatment practices for patients with hepatitis C virus infection in actual clinical practice, and to examine clinical outcomes in patients treated with interferon alpha-2b/ribavirin combination therapy in academically affiliated centres, private treatment centres and Veterans' Affairs treatment centres. METHODS: This multi-centre, retrospective, cohort study of 231 patients examined hepatitis C virus treatment practices in patients receiving interferon alpha-2b from January 1997 to May 2001 and explored outcomes in academically affiliated, private and Veterans' Affairs centres. RESULTS: Differences in treatment practice and use of diagnostic procedures were found. Genotype testing was under-utilized in non-academic sites (academic centres, 79.2%; private centres, 33.7%; Veterans' Affairs centres, 35.9%; P<0.001). Liver biopsies were performed less often in private sites (academic centres, 95.8%; private centres, 80.0%; Veterans' Affairs centres, 92.2%; P<0.01). End-of-treatment viral response (academic centres, 40.0%; private centres, 31.3%; Veterans' Affairs centres, 17.2%; P<0.05) was lower than that found in published trial data. Multivariate analysis revealed genotype 1 as the single significant predictor of treatment failure (P<0.01). CONCLUSIONS: Outside of the academic setting, there is significantly less diagnostic work-up performed prior to the initiation of hepatitis C virus therapy. This suggests a need for a standardization of care across treatment settings.

The psychometric properties of the Interpersonal Sensitivity Measure in social anxiety disorder.

The Interpersonal Sensitivity Measure (IPSM) was developed to assess hypersensitivity to interpersonal rejection, a suggested trait of depression-prone personality (Aust NZ J Psychiatry 23 (1989) 341). Although studies of the IPSM and interpersonal rejection sensitivity have primarily been conducted in depressed populations, it is important to investigate interpersonal rejection sensitivity as a relevant construct in the assessment of social anxiety. This study examined the psychometric properties of the IPSM in treatment-seeking individuals with social anxiety disorder. The results of this investigation support the convergent and divergent validity and internal consistency of the IPSM in socially anxious individuals. An exploratory factor analysis of the scale was also conducted after the original factor and subscale structure was shown to be a poor fit for the present data. Three factors emerged (Interpersonal Worry and Dependency, Low Self-Esteem, and Unassertive Interpersonal Behavior), and 29 items were retained. Because they demonstrated negative factor loadings on Factor 2, it is suggested that the scoring for four items of the original IPSM be reversed. In summary, the revised IPSM assesses three aspects of interpersonal rejection sensitivity and appears to be a valid and reliable instrument for its assessment in social anxiety disorder.

[Extradural hematoma of the posterior fossa]. / Hématome extradural de la fosse postérieure.

Extradural hematoma of the posterior fossa (EDHPF) is considered to be a rare complication of head injuries. In early reports, diagnosis was made only at the time of autopsy. Today, CT scanning prompts early diagnosis leading to better outcome. We report 20 consecutive patients observed over the last ten years who underwent surgery for EDHPF. This localization was found in 14,3% of all trauma patients operated for extradural hematoma. In our experience, EDHPF occurs in young adults with a clear male predominance. Vehicle accidents are the most frequent mechanism of injury. The main clinical presentation is subacute onset of signs (50% of our cases). Postoperative outcome was favorable in 19 of our patients (95%). We propose mandatory CT scanning that may have to be repeated as needed, to prevent delay in diagnosis and decision for surgery. Surgical removal of the EDHPF must be carried out as soon as possible as this is the only way to reduce morbidity and mortality.

[Subperiosteal hematoma of the orbit. Three cases]. / Hématome sub-périosté de l'orbite.

Orbital subdural hematoma should be considered in victims of head and face trauma with signs of exophthalmia. Early diagnosis and treatment, consisting of decompression, is mandatory to avoid long-term functional complications.

[Tuberculous abscess of the cerebellum. Apropos of a case]. / Abcès tuberculeux du cervelet. A propos d'un cas.

A 22-year-old Asian man developed intracranial hypertension with a 38 degrees C fever. Two months earlier, he had undergone surgery and medical treatment for tuberculous otomastoiditis and pulmonary tuberculosis. The CT scan revealed multiple tuberculous abscesses of the cerebellum. Histological, microbiological and biological proof of diagnosis was obtained. We advocate surgical treatment of intracranial tuberculous abscesses associated with antituberculosis chemotherapy for 18 months. The earlier the treatment, the better the prognosis. This pathology must be kept in mind when treating patients from countries with a high endemic rate of tuberculosis and suffering from immunodeficiency syndrome.

Ectopic expression of neurogenin 3 in neonatal pig pancreatic precursor cells induces (trans)differentiation to functional alpha cells.

AIMS/HYPOTHESIS: Neurogenin 3 (NEUROG3), a basic helix-loop-helix transcription factor that is needed for endocrine cell development in the embryonic pancreas, has been shown to induce transdifferentiation of duct cells from adult pancreas towards a neuro-endocrine phenotype. Our study explored the endocrine transdifferentiation potential of NEUROG3 in neonatal pancreatic precursor cells. MATERIALS AND METHODS: A replication-deficient adenovirus expressing Neurog3 and green fluorescent protein (GFP) (Ad-NEUROG3) was used to infect neonatal pig pancreatic cell preparations enriched for endocrine islet and cytokeratin-positive precursor cells. GFP-positive cells were sorted using flow cytometry on days 3 and 8 after infection and characterised at the transcript and protein level. For in vivo experiments, the total population of Ad-NEUROG3-infected pancreatic cells was transplanted, then later removed for determination of graft hormone content and immunohistochemistry. RESULTS: Among the GFP-positive cells, the fraction of precursor cells decreased by more than 85% at day 8 after infection, while the fraction of glucagon-positive cells increased 2.5-fold and the beta cell number remained the same. Transplantation of the Ad-NEUROG3-infected pancreatic cell preparation failed to reverse streptozotocin-induced hyperglycaemia, while non-infected cells and a control cell preparation infected with replication-deficient adenovirus expressing only GFP were able to do so. At day 109 after transplantation, kidneys grafted with Ad-NEUROG3-infected pancreatic cells contained significantly decreased insulin and increased glucagon levels. Abundant glucagon-immunopositive cells were seen in Ad-NEUROG3-infected grafts, which were virtually devoid of proliferating insulin-positive cells. CONCLUSIONS/INTERPRETATION: In summary, adenoviral delivery of NEUROG3 to pancreatic precursor cells from neonatal pig pancreas promotes alpha cell differentiation in vitro and in vivo.

Effects of gallstone solvents on commonly used catheters.

PURPOSE: To determine what interaction and effect different cholesterol gallstone solvents have on catheters used for gallstone chemolysis. MATERIALS AND METHODS: Five types of catheters used for biliary procedures were chosen: polyethylene, Percuflex, silicon, Silitek, and polyurethane. The solvents chosen were methyl tert-butyl ether, ethyl propionate, isopropyl acetate, and N-propyl acetate. After incubation of the catheters in the solvents for 72 hours, they were air dried. Weight and area changes were determined for each catheter. Additionally, carbon-13 nuclear magnetic resonance (NMR) spectroscopy was performed for analysis of composition changes. RESULTS: Three catheters--silicone, Silitek, and polyurethane--showed changes in their physical characteristics that would make them less desirable for stone chemolysis. The silicone catheter showed changes in elastic texture as well as marked weight reduction. The Silitek and polyurethane catheters had similar, but less dramatic changes. C-13 NMR analysis of collected solvents showed that commonly used plasticizers were leached out of some catheters. CONCLUSION: These results suggest that all catheters are not suitable for use with all solvents. The choice of catheter should be made based on the solvent in use. The polyethylene catheter performed best under the conditions and endpoints used in this study.

Comparison of quality of life, work productivity and medical resource utilization of peginterferon alpha 2a vs the combination of interferon alpha 2b plus ribavirin as initial treatment in patients with chronic hepatitis C.

The on-treatment impact of interferon-based therapies on quality of life (QOL), work productivity, and medical resource utilization has not been systematically studied. We evaluated the effects of treatment with peginterferon alpha (pegIFNalpha) 2a monotherapy and the combination of interferon alpha (IFNalpha) 2b plus ribavirin (RBV) on health-related QOL, work productivity and resource utilization. A total of 412 patients with hepatitis C infection were randomized to open-label treatment with either pegIFNalpha 2a (n = 206) or IFNalpha 2b/RBV (n = 206). PegIFNalpha 2a was administered subcutaneously at a dose of 180 microg once weekly for 48 weeks; and IFNalpha 2b/RBV at doses of 3 MU thrice weekly subcutaneously and 1000-1200 mg/day orally. Outcome measures included the SF-36 Health Survey Questionnaire and additional generic and specific scales. During treatment, for all SF-36 summary and Hepatitis Quality of Life Questionnaire (HQLQ)-specific scales, the pegIFNalpha 2a group experienced less impairment than did the IFNalpha 2b/RBV patients. The between-treatment differences were significant for many of the scores particularly in the first 24 weeks of treatment. Across all measures of work functioning and productivity at each visit, patients randomized to pegIFNalpha 2a treatment showed less impairment relative to the group treated with IFNalpha 2b/RBV. Hence treatment with pegIFNalpha 2a relative to IFNalpha 2b/RBV minimizes the adverse impact of therapy on health-related QOL. Patients randomized to pegIFNalpha 2a had improved work productivity, less activity impairment, decreased need for prescription drugs to treat adverse effects, and better adherence to therapy.

Cirugía convencional y stentor en aneurisma de aorta abdominal gigante: presentación de caso clínico y revisión bilbiográfica / Conventional surgery and stentor in giant abdominal aortic aneurism: case report and bibliographic review

El aneurisma aórtico abdominal es una enfermedad arterio-esclerótica que complica la vida del paciente en caso de que sangre. Dentro de las apreciaciones generales, si el aneurisma es mayor a 6 cm de diámetro debe ser intervenido quirúrgicamente. En caso de tratarlo en el momento del sangrado se convierte en una emergencia quirúrgica, con un 50 por ciento de mortalidad. Actualmente se cuentan con métodos diagnósticos precisos y no muy costosos, como la ecografía abdominal con doppler color y la tradicional arteriografía aórtica. Su tratamiento quirúrgico ha sido innovado por técnicas hemodinámicas de cateterismo con colocación de endoprótesis expandibles (stentors). Presentamos el caso de un paciente de 74 años...