Indocyanine green: intracellular uptake and phototherapeutic effects in vitro

Indocyanine green (ICG; absorption peak in human plasma 805 nm) was investigated for ICG-mediated phototherapy in vitro. The cellular uptake of ICG (1 microM-50 microM) into HaCaT keratinocytes after an incubation period of 24 h increased up to an intracellular ICG concentration of 12.1 +/- 1.3 nmol per 10(6) cells. To examine dose dependent phototoxic effects in vitro, keratinocytes were incubated with 0 microM-50 microM ICG for 24 h and irradiated by a diode laser (805 nm) with different energy densities (0, 12, 24, 48 J cm-2). All applied ICG concentrations except for 5 microM yielded a cell killing effect in combination with irradiation depending significantly on ICG concentration and light dose. Cell viability for dark control and cells incubated with 50 microM ICG and irradiated with 48 J cm-2 was 0.82 +/- 0.15 and 0.07 +/- 0.02, respectively. Sodium azide (100 mM), a quencher of reactive oxygen species, inhibited significantly the cell killing using 50 microM ICG and 24 J cm-2. Taken together, photoactivation of ICG by irradiation with a diode laser was shown to induce effectively cell killing of HaCaT keratinocytes. Moreover, this effect was inhibited by sodium azide, thus irradiation of ICG might induce a photodynamic reaction.     

Spontaneous bacterial peritonitis in patients with ventriculoperitoneal shunts

A questionnaire to evaluate the needs of dialytic patients and the burden that these have on the health service and staff, was formulated by the nurses. The results showed how the patient's case history indicate, significantly, not only personal and subjective aspects (e.g. interpersonal relationships), but also how they construct their relationships with the hospital and its service (including the hospital staff). This opens up certain reflections on what role communication and information play within the hospital structure.     

The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.     

Effect of insulin versus sulfonylurea therapy on cardiovascular risk factors and fibrinolysis in type II diabetes

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis. 2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients. 3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. N omega-Nitro-L-arginine methyl ester (L-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease. 4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lymphomononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters. 6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.     

Ventricular perforation associated with central venous introducer-dilator systems

BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. METHODS: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.     

The limit of viability--neonatal outcome of infants born at 22 to 25 weeks' gestation

BACKGROUND: With improved survival of preterm infants, questions have been raised about the limit of viability. To provide better information and counseling for parents of infants about to be delivered after 22 to 25 weeks' gestation, we evaluated the mortality and neonatal morbidity of preterm infants born at these gestational ages. METHODS: We studied retrospectively all 142 infants born at 22 to 25 weeks' gestation (as judged by best obstetrical estimate) from May 1988 through September 1991 in a single hospital. Mortality in the first six months, including stillbirths, and neonatal morbidity (i.e., the presence of intracranial pathologic conditions, chronic lung disease, and retinopathy of prematurity) were analyzed. RESULTS: Fifty-six infants (39 percent) survived for six months. Survival improved with increasing gestational age; none of 29 infants born at 22 weeks' gestation survived, as compared with 6 of 40 (15 percent) born at 23 weeks, 19 of 34 (56 percent) born at 24 weeks, and 31 of 39 (79 percent) born at 25 weeks. There were seven stillbirths at 22 weeks' gestation and four stillbirths at 23 weeks. The more immature the infant, the higher the incidence of neonatal complications as determined by the number of days of mechanical ventilation, the length of the hospital stay, and the presence of retinopathy of prematurity, periventricular or intraventricular hemorrhage, or periventricular leukomalacia. Only 2 percent of infants born at 23 weeks' gestation survived without severe abnormalities on cranial ultrasonography, as compared with 21 percent of those born at 24 weeks and 69 percent of those born at 25 weeks. CONCLUSIONS: We believe that aggressive resuscitation of infants born at 25 weeks' gestation is indicated, but not of those born at 22 weeks. Whether the occasional child who is born at 23 or 24 weeks' gestation and does well justifies the considerable mortality and morbidity of the majority is a question that should be discussed by parents, health care providers, and society.