Reactive hyperemia and tissue-type plasminogen activator release in hypertensive men.

A relationship may exist between endothelial-mediated vasodilation and tissue-type plasminogen activator (t-PA) release. However, the existing evidence is mainly based upon exogenous agonist administration, and needs testing under more physiological conditions. We evaluated the link between t-PA, the key fibrinolytic factor in man, and forearm reactive hyperemia, a model of endogenous endothelial-mediated vasodilation, in 13 uncomplicated hypertensive subjects and six elderly hypertensive patients with atherosclerotic peripheral vascular disease and hypercholesterolemia (i.e a group in whom post-ischemic hyperemia was probably defective because of dysfunctional endothelium). To characterize further the phenomenon, 29 additional uncomplicated hypertensive patients underwent intra-arterial drug infusions. Study variables were forearm blood flow (strain-gauge plethysmography), arterial and venous concentrations of t-PA mass concentrations, and calculated net release (forearm plasma flow x veno-arterial differences). Reactive hyperemia was induced by inflating a cuff midway between systolic and diastolic pressure for 10 min; blood and forearm blood flow were sampled before and after cuff release. Post-ischemic t-PA release increased in uncomplicated hypertensives, and did not change in hypercholesterolemic atherosclerotic patients in whom post-ischemic vasodilation was negligible. Local adenosine (n = 9), acetylcholine (n = 12) and bradykinin (n = 8) vasodilated similarly, but only bradykinin increased t-PA release. Thus, reactive hyperemia stimulates t-PA release, and that relationship is altered when endothelium is dysfunctional. Release of t-PA is independent of forearm vasodilatation, adenosine or biological products of muscarinic stimulation and may, perhaps, be related to the activity of the endogenous kininogen/kinin system.     

Distribution of [3H]-d-penicillamine in mouse kidney

Summary ³H-labeled d-penicillamine has been injected in mice in order to study by autoradiography its distribution in the kidney. The results show heavy accumulation of the drug in the epithelial cells of the proximal tubules of the kidney, whereas glomeruli and distal tubules do not show any significant accumulation. This peculiar tropism of penicillamine to proximal tubules is entirely consistent with the Heymann's nephritis model suggested by Bacon as a pathogenetic model for penicillamine-induced nephropathy.     

Vaccination against Haemophilus influenzae type b in Uruguay: experience and impact]

Between 1979 and 1994, epidemiological surveillance of meningitides in Uruguay showed a progressive increase in suppurative meningitides due mainly to Neisseria meningitidis and Haemophilus influenzae type b (Hib). The cases were concentrated in children under 5; however, among the cases caused by Hib, 70% affected children from 1 to 11 months old. Facing this situation, the Ministry of Public Health resolved, as of August 1994, to include the Hib vaccine in the country's Expanded Program on Immunization, which has been in place since 1982. The Hib vaccination is done without charge and is obligatory for all children under 5 years of age. It is done using the following series of vaccinations: a) three doses, given at 2, 4, and 6 months, with a booster dose at age 1; b) children from 7 to 11 months old receive two doses two months apart and a booster dose a year later; and c) a single dose for children 12 months to 4 years old. Between August and December 1994 a coverage rate of 76.6% was reached among children between 2 months and 4 years old, and the coverage has remained above 80% in the new cohorts. In Uruguay, this vaccination strategy had a spectacular impact on morbidity and mortality due to meningitides caused by Hib. One of the results was that the incidence of 15.6 per 100,000 registered in children under 5 in the prevaccination years declined to 0.03 per 100,000 in 1996.     

Introduction of a conjugate vaccine against Hib in Chile and Uruguay]

In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib) has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with the support of scientific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.     

Test-retest evaluation of HAT-QoL and SF-36 in an HIV-seropositive sample

We sought to correct previously reported psychometric and content problems of the HIV/AIDS-Targeted Quality of Life Instrument (HAT-QoL) and to assess test-retest reliability of this revised HAT-QoL as well as the MOS 36-Item Short-Form Health Survey (SF-36) when used in an HIV-seropositive outpatient sample. A total of 153 participants randomly sampled from an HIV specialty and general medical clinics completed a test booklet that contained HAT-QoL and the SF-36; a random subsample of 60 participants were asked to return in approximately two weeks to complete the instruments again. Using the baseline sample, internal consistency coefficients of all final HAT-QoL dimensions were > or =0.80. The retest subsample, for which there were no significantly different characteristics than the baseline sample, completed the instruments again an average of 14.7 days after baseline completion. For HAT-QoL, only one (Provider Trust) of the nine dimensions revealed a significant test-retest difference (+5.9, p=0.05). All HAT-QoL intraclass correlation coefficients (ICCs) were > or =0.64 (seven values were > or =0.73). All effect sizes were small. For SF-36, two dimensions (Physical Functioning and Social Functioning) revealed significant test-retest differences, and one dimension (Mental Health) revealed a difference approaching significance (p=0.06). The SF-36 ICCs were similar to those for HAT-QoL, with the exception of three dimensions--Vitality, Role-Emotional and Mental Health (all were<0.56). Though most effect sizes were small, Social Functioning and Mental Health estimates were approaching more moderate effect sizes. HAT-QoL reveals considerable short-term stability and has psychometric features in the seropositive population comparable to instruments such as SF-36, while obtaining unique information.     

The neuropsychology of borderline personality disorder: a meta-analysis and review

The neuropsychological profile of borderline personality disorder (BPD) is unclear. Past investigations have produced seemingly inconsistent results concerning precisely what neuropsychological deficits characterize the patient with BPD. A meta-analysis of 10 studies was conducted comparing BPD and healthy comparison groups on selected neuropsychological measures comprising six domains of functioning: attention, cognitive flexibility, learning and memory, planning, speeded processing, and visuospatial abilities. BPD participants performed more poorly than controls across all neuropsychological domains, with mean effect sizes (Cohen's d) ranging from − 0.29 for cognitive flexibility to − 1.43 for planning. The results suggest that persons with BPD perform more poorly than healthy comparison groups in multiple neurocognitive domains and that these deficits may be more strongly lateralized to the right hemisphere. Although neuropsychological testing appears to be sensitive to the neurocognitive deficits of BPD, the clinical utility of these results is limited. Implications of these findings for future neurocognitive investigations of BPD are discussed.     

Lyell's syndrome

Lyell's syndrome, or toxic epidermal necrolysis, is a rare, potentially life-threatening mucocutaneous disease, usually provoked by the administration of a drug and characterized by acute necrosis of the epidermis. The drugs most frequently incriminated are nonsteroidal anti-inflammatory drugs, chemotherapics, antibiotics, and anticonvulsants. An immunologic response to immunocomplexes formed by metabolites of the causal drug and the common tissue antigens is thought to be responsible for this disorder. Preceded by fever, general malaise, and other flu-like symptoms, bullous and erosive lesions involve oral, ocular, and genital mucosae; and vast areas of the skin with extensive dermoepidermal detachments. The loss of fluid and electrolytes and supervening infections lead to a severe general condition, often with fatal outcome. Treatment is based on the administration of fluids, electrolytes, and albumin. The use of systemic corticosteroids is controversial. Plasmapheresis and hyperbaric oxygen proved to be useful. The employment of high doses of IV immunoglobulins is a novel, valid, and promising treatment.     

Porins of Pseudomonas aeruginosa induce release of tumor necrosis factor alpha and interleukin-6 by human leukocytes.

The aim of this study was to examine the ability of Pseudomonas aeruginosa components to induce release of cytokines from human leukocytes. Human whole-blood cultures were incubated with several concentrations of purified P. aeruginosa products, including porins, exomucopolysaccharide, lipopolysaccharide, and toxin A. Supernatants were assayed for tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) activities. All of the P. aeruginosa components except toxin A were able to stimulate the release of both cytokines. On a weight basis, porins were as effective as lipopolysaccharide and significantly more effective than exomucopolysaccharide in inducing IL-6 release (P < 0.05). Moreover, porins were more potent than either exomucopolysaccharide or lipopolysaccharide in inducing TNF-alpha release (P < 0.05). Further experiments using isolated leukocytes suggested that monocytes were the cell population predominantly responsible for the production of both cytokines. These data indicate that P. aeruginosa porins are able to induce significant cytokine production. These components may be responsible for the chronically overactive inflammatory response associated with persistent lung infection in cystic fibrosis patients.