Exercise Perception and Behaviors in Individuals Living with Primary Immunodeficiency Disease.

BACKGROUND: Routine exercise has been established as an effective way to improve overall health. The value of exercise has been established in many diseases, however, there are no studies investigating the impact of exercise for individuals with primary immunodeficiency disease (PID). The purpose of this study was to investigate exercise perceptions and behaviors in individuals diagnosed with PID. METHODS: An online survey was distributed over a four-week period. RESULTS: Of the 264 responses collected, most were females, 45-54 years old. Respondents reported a measurable loss of function impairing their daily activities due to loss of mobility/physical activity (41.32%), or loss of lung/pulmonary function (40.08%,). They felt exercise decreased stress level and improved their mental well-being (46.25%). Some indicated they participate in exercise (33.20%), while 36.84% had not participated in exercise for at least 1 year. Exercise was limited primarily due to fatigue (86.97%). CONCLUSION: Exercise is important for those with chronic medical conditions. Most individuals living with PID can participate in low/moderate physical activity, but struggle with vigorous physical activity, since fatigue is the greatest barrier. Respondents view exercise as beneficial, and would like to increase participation in an exercise program.

Surgical results and survival of older patients with unsuspected N2 (stage IIIA) non-small cell lung cancer.

PURPOSES: The optimal treatment of N2 non-small cell lung cancer (NSCLC) in older patients is still debate and represent an important treatment and ethical problem. PATIENTS AND METHODS: Between January 2000 to December 2010, 273 older patients underwent lung resection for (NSCLC). RESULTS: The overall-operative mortality was 9.5%. Risk factors for in-hospital mortality were pneumonectomy and poli-vasculopathy. One, 3 and 5-year survival were 73%, 23% and 16% respectively. CONCLUSIONS: In potentially operable older patients with NSCLC we need to make every effort to exclude N2 involvement because very poor long-term survival. Pneumonectomy in older patients gains prohibitive in-hospital mortality.

Development and validation of the Self-Management Assessment for the Residuum and prosThesis system designed for persons with limb loss (SMART).

OBJECTIVE: To develop a system of reliable and valid knowledge assessments of self-management in persons with lower limb loss, along with the accompanying targeted educational interventions (TEIs), known as the Self-Management Assessment for the Residuum and prosThesis (SMART) system. DESIGN: This 2-phase study used mixed methodology. Phase 1 was development, face validation, and content validation of the 60-item knowledge assessment measure (SMART 60) and the TEI. Phase 2 assessed internal consistency reliability using Kuder-Richardson Formula 20 and the creation of the SMART system, consisting of modules developed from the SMART 60. Validity of the measures using known groups' comparison was analyzed by comparing clinicians (prosthetists and physical therapists) with persons with lower limb loss. Participants were recruited from the Amputee Coalition National Conference in 2018 and 2019. RESULTS: A total of 140 participants completed this study. Four modules from the SMART 60 were created and designed to integrate as a system. Face validity survey average scores found that 9/10 participants either agreed or strongly agreed that the SMART system has high readability, perceived usefulness, and value for both new and experienced prosthetic users. Measure length ranged from 10 to 45 items with a reliability ranging from Kuder-Richardson Formula 20 = 0.70-0.82. The SMART system demonstrated known-groups validity ( p < 0.05). CONCLUSION: The SMART system is an integrated series of self-management knowledge assessments with reasonable to good internal consistency reliability and known-groups validity. The TEIs provide directed solutions to identified knowledge gaps on the assessments.

Differential responses of genes and enzymes associated with ROS protective responses in the sugarcane smut fungus.

The fungal pathogen Sporisorium scitamineum causes sugarcane smut disease. We have previously shown that resistant sugarcane plants induce ROS, coinciding with a delay in fungal colonization. Here, we investigated whether the fungus modifies the enzymatic antioxidant system in vitro and when colonizing sugarcane tissues in response to ROS. In vitro, the exposure to ROS did not affect cell integrity, and a combination of superoxide dismutases (SOD) and catalases (CAT) were active. In vitro, the fungus did not alter the expression of the transcriptional regulator Yap1 and the effector Pep1. The fungus activated distinct enzymes when colonizing plant tissues. Instead of CAT, S. scitamineum induced glutathione peroxidase (Gpx) expression only when colonizing smut-resistant plants. Yap1 had an earlier expression in both smut-susceptible and -resistant plants, with no apparent correlation with the expression of antioxidant genes sod, cat, gpx, or external redox imbalance. The expression of the effector pep1 was induced only in smut-resistant plants, potentially in response to ROS. These results collectively suggest that S. scitamineum copes with oxidative stress by inducing different mechanisms depending on the conditions (in vitro/in planta) and intensity of ROS. Moreover, the effector Pep1 is responsive to the stress imposed only by the sugarcane resistant genotype.

Development of an optical RNA-based aptasensor for C-reactive protein.

The development of a RNA-aptamer-based optical biosensor (aptasensor) for C-reactive protein (CRP) is reported. CRP is an important clinical biomarker; it was the first acute-phase protein to be discovered (1930) and is a sensitive systemic marker of inflammation and tissue damage. It has also a prognostic value for patients with acute coronary syndrome. The average concentration of CRP in serum is 0.8 ppm and it increases in response to a variety of inflammatory stimuli, such as trauma, tissue necrosis, infection and myocardial infarction. The interaction between the 44-base RNA aptamer and the target analyte CRP is studied. In particular, the influence of the aptamer immobilization procedure (chemistry, length, concentration), as well as the binding conditions, i.e., the influence on the binding of different buffers, the presence of Ca2+ ion and the specificity (against human serum albumin) have been evaluated. Using the best working conditions, we achieved a detection limit of 0.005 ppm, with good selectivity towards human serum albumin. Some preliminary experiments in serum are reported.

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

To elucidate mechanisms of glucagon-induced bicarbonate-rich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pHi) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pHi, significantly stimulates the Cl-/HCO3- exchange activity. The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3- exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3- exchange was individually blocked by two specific and selective inhibitors of protein kinase A, Rp-cAMPs (10 microM) and H-89 (30 microM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl- channel blocker, NPPB (10 microM), showed no effect on either the basal or the glucagon-stimulated Cl-/HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 microM), completely blocked the glucagon stimulation of the Cl-/HCO3- exchange; however, this effect was achieved through a significant inhibition of the glucagon-stimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3- exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pHi or at acid pHi values. In contrast, glucagon, at basal pHi, stimulated the Na(+)-HCO3- symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3- exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis.

Laser photocoagulation for neovascular age-related macular degeneration.

BACKGROUND: Laser photocoagulation was the first treatment introduced to try to halt the progression of neovascular age-related macular degeneration (AMD), in which newly formed vessels or choroidal neovascularisation (CNV) grow under the macula leading to the occurrence of a scotoma or blind spot in the central visual field. OBJECTIVES: The aim of this review was to examine the effects of laser photocoagulation for neovascular AMD. SEARCH STRATEGY: We searched the CENTRAL, MEDLINE, EMBASE, LILACS, NRR and ZETOC in March 2007. SELECTION CRITERIA: We included randomised trials of laser photocoagulation in people with CNV due to AMD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The risk ratio (RR) of severe visual loss (loss of six or more lines of visual acuity) was estimated at three months and two years after treatment. MAIN RESULTS: Fifteen trials were included in the review (2064 participants). Three types of photocoagulation were used in the trials: direct photocoagulation of the entire CNV (11 trials), perifoveal photocoagulation (one trial) and grid photocoagulation (three trials). In 12 trials the control group was observation only. One trial compared photocoagulation to submacular surgery and two trials compared different lasers. Data on the progression of visual loss could be extracted from five of the eight trials of direct photocoagulation of the CNV versus observation. The treatment effect was in the direction of harm in all studies at three months follow up (RR 1.41, 95% confidence intervals (CI) 1.08 to 1.82). After two years the treatment effect was in the direction of benefit (RR 0.67, 95% CI 0.53 to 0.83). These studies were clinically heterogeneous with participants having CNV lesions in different locations and different baseline visual acuities. There was little evidence of statistical heterogeneity at three months but substantial statistical heterogeneity at two years. However, all treatment effects in the individual trials were in the direction of benefit. One study comparing perifoveal photocoagulation or observation of subfoveal CNV found benefits that were statistically significant only at two years (RR 0.36, 95% CI 0.18 to 0.72). Other comparisons did not demonstrate differences. AUTHORS' CONCLUSIONS: In the medium to long term laser photocoagulation of CNV slows the progression of visual loss in people with neovascular AMD. However, it is associated with an increased risk of visual loss immediately after treatment and this period may be longer in people with subfoveal AMD. With the advent of modern pharmacological therapies, and concern for the impact of iatrogenic scotoma in subfoveal CNV, laser photocoagulation of subfoveal CNV is not recommended. No studies have compared photocoagulation with modern pharmacological agents for AMD for non-subfoveal CNV.

Intravitreal bevacizumab therapy for choroidal neovascularization secondary to age-related macular degeneration: 6-month results of an open-label uncontrolled clinical study.

PURPOSE: To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. METHODS: Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. RESULTS: At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 microm (p<0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean BCVA slightly decreased from 20/100(-1) to 20/125(-3) (not significant, p=0.40). Mean CRT was still inferior to baseline (305 microm, p<0.01). Mean lesion GLD was 4186 microm, not different from baseline values (p=0.59), but superior to 3-month mean GLD (p<0.01). Significant visual field defects or endothelial cell losses were not detected at 3 and 6 months. Laboratory testing did not reveal any clinically significant deviations compared to baseline values. CONCLUSIONS: Intravitreal therapy using bevacizumab over 6 months showed stabilization of visual acuity and choroidal neovascularization activity; the safety data were convincing.

Occurrence of full-thickness macular hole complicating Stargardt disease with ABCR mutation.

PURPOSE: To report an unusual episode of full-thickness macular hole complicating Stargardt disease with an ABCR mutation. METHODS: Case report . RESULTS: Fundus examination of a 20-year-old healthy man showed typical fundus manifestation with yellowish-round or fish-like flecks associated with vitreous macular adhesion and a round punched-out area in the right eye. Optical coherence tomography (OCT) illustrated a full-thickness macular hole. Molecular genetic examination of the ABCR gene showed two heterozygous missense mutations: R1108C (CGC-->TGC) in exon 22 and a splicing mutation IVS6--> 1GT - described in the literature in association with Stargardt disease. CONCLUSIONS: Macular hole was once described in other inherited retinal degenerations (Best disease and Bietti crystal line retinopathy). The pathogenesis gives rise to a host of speculations: widespread alteration of the retinal pigment epithelium; inflammatory mechanisms; a minor trauma which might cause subretinal fibrosis. Surgical procedures were not performed on our patient after his ophthalmologic history and findings were considered.

Clear corneal incision of 2.75 mm for cataract surgery induces little change of astigmatism in eyes with low preoperative corneal cylinder.

PURPOSE: To assess the early astigmatic effect induced by 2.75 mm clear cornea incisions with different locations for cataract surgery. METHODS: A total of 146 eyes of different patients were studied prospectively. Cataract surgery was performed by three surgeons, two using a temporal approach and one using a superior approach. For both approaches, the site of the 2.75 mm incision was allowed to vary slightly according to the characteristics of the eye and orbit. Computerized videokeratography was used to measure corneal astigmatism before surgery and after 1, 4, and 12 weeks. Corneal astigmatism was recorded as cylinder and axis and it was then converted to 2 power vector. Model based prediction and comparisons were made for the most commonly used corneal incision sites: 12 (both eyes), 2 (left eye), and 8 (right eye) o'clock meridian. RESULTS: After 3 months the differences in corneal astigmatism (JCC 0 ) between the incisions performed at 12 and 2 o'clock were not statistically significant (-0.08, 95% CI: -0.19, -0.02); the differences in JCC 0 between incisions at 12 and 8 o'clock were -0.17 (95% CI: -0.30, -0.05; p<0.01). After 3 months the change in JCC 0 for the patients with 0.5 D with-the-rule preoperatively were -0.32 (95% CI: -0.44, 0.21; p<0.01) for incisions at 12; -0.24 (95% CI: -0.36, 0.13; p<0.01) for incisions at 2; and -0.15 (95% CI: -0.27, -0.03; p<0.05) for incisions at 8. After 3 months the changes of JCC 0 for the patients with -0.5 D against-the-rule pre-operatively were 0.10 (95% CI: 0.04, 0.23) for incision at 12; 0.18 (95% CI: 0.04, 0.32; p<0.05) for incisions at 2; and 0.27 (95% CI: 0.14, 0.40; p<0.01) for incisions at 8 o'clock. The oblique astigmatic vector (JCC 45 ) was very modest in this sample before surgery and underwent minimal and nonsignificant change after it. CONCLUSIONS: This study has shown that a 2.75 mm clear corneal incision causes a small change of corneal cylinder regardless of incision site.

Plexiform vascular structures in the human digital dermal layer: a SEM--corrosion casting morphological study.

This study aimed to describe the impressive diversity of vascular plexiform structures of the hypodermal layer of human skin. We chose the human body site with the highest concentration of dermal corpuscles, the human digit, and processed it with the corrosion casting technique and scanning electron microscopy analysis (SEM). This approach proved to be the best tool to study these microvascular architectures, free from any interference by surrounding tissues. We took high-definition pictures of the vascular network of sweat glands, thermoreceptorial and tactile corpuscles, the vessels constituting the glomic bodies and those feeding the hair follicles. We observed that the three-dimensional disposition of these vessels strictly depends on the shape of the corpuscles supplied. We could see the tubular vascularization of the excretory duct of sweat glands and the ovoid one feeding their bodies, sometimes made up of two lobes. In some cases, knowledge of these morphological data regarding the normal disposition in space and intrinsic vascularization structure of the dermal corpuscles can help to explain many of the physiopathological changes occurring during chronic microangiopathic diseases.

Thrombosis in atherogenesis.

This review addresses the question of the involvement of fibrin in the development of atherosclerotic plaques. Numerous studies in the older literature demonstrated the presence of fibrinogen and/or fibrin in plaques, but the techniques that were available (mainly immunochemistry and immunohistochemistry with polyclonal antifibrinogen antibodies) did not clearly distinguish fibrinogen from fibrin or fibrinogen/fibrin degradation products. Some of these studies suggested that the fibrinogen-related protein within lesions resulted from incorporation of thrombi into lesions, while other studies suggested that fibrinogen itself entered the vessel wall. Newer studies by the authors and collaborators used specific antibodies for various fibrinopeptides to quantitate fibrinogen, fibrin I, fibrin II, and fragment X in thrombi and different histologic types of plaques. These studies showed that normal aortas contained fibrinogen and that fatty and fibrous plaques contained fibrinogen, fibrin I, and fibrin II, while complicated plaques contained fibrin II and fragment X, indicating a progression from fibrinogen to fibrin and fibrinogen/fibrin degradation products in parallel with increasing severity of the lesions. Later studies by the authors and collaborators used a sensitive immunohistochemical technique with monoclonal antibodies to demonstrate the distribution of fibrinogen-related antigens. Patterns suggesting incorporation of thrombi were seen, as were patterns suggesting formation of fibrin in association with arterial wall monocyte/macrophages and smooth muscle cells. The data from these various studies suggest the possibility that fibrin formation occurs within the arterial wall and contributes to plaque formation.

Age-related differences in the metabolism of sulphite to sulphate and in the identification of sulphur trioxide radical in human polymorphonuclear leukocytes.

Sulphite oxidation and sulphur trioxide radical formation were studied in polymorphonuclear leukocytes (PMNs) isolated from healthy young, old and centenarian donors and from patients with Down's syndrome. The sulphur radical formation measured by electron spin resonance spectroscopy-spin trapping (EPR-ST) was correlated with the activity of sulphite oxidase and with the rate of sulphite oxidation to sulphate by PMNs. Sulphite metabolism was studied both in resting, and phorbol myristate acetate (PMA) stimulated freshly isolated cells. The rate of sulphur trioxide radical formation was demonstrated by use of the spin trapping agent 5,5-dimethyl-1-pyroline-1-oxide (DMPO) with subsequent formation of an adduct. The intensity of adduct formation was most intense in cells with low sulphite oxidase activity, while a mixture of the adduct and of DMPO hydroxyl radical was mainly observed in cells with high sulphite oxidase activity. Furthermore, experiments carried out on purified sulphite oxidase showed that in the presence of sulphite the enzyme could also give rise to a DMPO-OH adduct. Sulphite oxidase activity in cells isolated from healthy young and old donors was positive correlated with both rates of sulphur trioxide radical formation and sulphite oxidation to sulphate, respectively. However, sulphite oxidase activity in cells isolated from centenarians and patients with Down's syndrome seems to loose partly its rate of oxidising sulphite to sulphate. The intensity of the sulphur centred radical adduct increased in the two latter groups of population and the radical observed was predominantly sulphur trioxide radical.

Low molecular weight fibrinogen degradation products stimulate the release of growth factors from endothelial cells.

Cultured porcine aortic endothelial cells (PAEC) constitutively produce and secrete in their culture medium mitogens collectively called endothelial cell-derived growth factors (EDGFs). Incubation of PAEC with fibrinogen-degradation products (FDPs) obtained by plasmin digestion of highly purified fibrinogen caused an increased release of EDGFs, as assessed by [3H]-thymidine incorporation in 3T3 mouse fibroblasts. The effect was time-dependent and correlated with the degree of fibrinogenolysis. It was accompanied by elongation of the cells. Neither increase in EDGFs release nor cell damage was observed when non-degraded fibrinogen was incubated with endothelial cells. Low molecular weight fibrinogen degradation products (LMWFDPs) (M(r) less than or equal to 10,000), and the higher molecular weight fibrinogen fragments D and E were tested under the same conditions. Only the LMWFDPs caused elongation and damage to PAEC and a marked stimulation (up to 12 fold) of EDGFs release. A low density growth assay revealed that the released EDGFs were mitogenically active on the same PAEC. The activity of the released EDGFs was time and dose dependent on both 3T3 fibroblasts and PAEC, indicating that LMWFDPs caused enhanced release of EDGFs that can act in paracrine and autocrine fashion. This study suggests an additional role for fibrinogenolysis contributing to wound healing, and possibly to atherosclerosis.

Influence of ACTH-(1-24) on free radical levels in the blood of haemorrhage-shocked rats: direct ex vivo detection by electron spin resonance spectrometry.

1. The influence of ACTH-(1-24) on the blood levels of highly reactive free radicals in haemorrhagic shock was studied in rats. 2. Volume-controlled haemorrhagic shock was produced in adult rats under general anaesthesia (urethane, 1.25 g kg-1 intraperitoneally) by stepwise bleeding until mean arterial pressure stabilized at 20-23 mmHg. Rats were intravenously (i.v.) treated with either ACTH-(1-24) (160 micrograms kg-1 in a volume of 1 ml kg-1) or equivolume saline. Free radicals were measured in arterial blood by electron spin resonance spectrometry using an ex vivo method that avoids injection of the spin-trapping agent (alpha-phenyl-N-tert-butylnitrone). 3. Blood levels of free radicals were 6490 +/- 273 [arbitrary units (a.u.) ml-1 whole blood, before starting bleeding, and 30762 +/- 2650 after bleeding termination (means +/- s.e. mean of the values obtained in all experimental groups). All rats treated with saline died within 30 min, their blood levels of free radicals being 35450 +/- 5450 a.u. ml-1 blood, 15 min after treatment. Treatment with ACTH-(1-24) produced a rapid and sustained restoration of arterial pressure, pulse pressure, heart rate and respiratory function, with 100% survival at the end of the observation period (2 h); this was associated with an impressive reduction in the blood levels of free radicals, that were 12807 +/- 2995, 10462 +/- 2850, 12294 +/- 4120, and 10360 +/- 2080 a.u. ml-1 blood, 15, 30, 60 and 120 min after ACTH-(1-24) administration, respectively. 4. These results provide a direct demonstration that (i) in haemorrhagic shock there is a rapid and massive production of highly reactive free radicals, and that (ii) the sustained restoration of cardiovascular and respiratory functions induced by the i.v. injection of ACTH-(1-24) is associated with a substantial reduction of free radical blood levels. It is suggested that ACTH-(1-24) prevents the burst of free radical generation during blood mobilisation and subsequent tissue reperfusion, and this may be an important component of its mechanism of action in effectively preventing death for haemorrhagic shock.

Metabolism in rat liver microsomes of the nitroxide spin probe tempol.

Paramagnetic nitroxide spin labels have been extensively used to probe various biophysical and biochemical properties of the cellular environment. Recently nitroxides have been proposed as contrast enhancing agents in proton magnetic resonance imaging and contrast enhancement has been demonstrated in animal studies. Nitroxides, possessing a stable unpaired electron, increases the relaxation rates of protons, providing an enhancement of contrast. Nitroxides are metabolized intracellularly principally via reversible reduction to hydroxylamines. Rates of reduction depend on the physical characteristics of the nitroxides, in general 5-membered pyrrolidine ring are reduced more slowly than those with a 6-membered piperidine ring. Oxidation back to the nitroxide is relevant for lipid soluble hydroxylamines, while is low for water soluble ones. It is known that nitroxides are metabolized by subcellular fractions (cytosol, mitochondria, microsomes), though the enzymatic and non-enzymatic systems involved are poorly characterized. In the present study, the first of the necessary steps toward a systematic study of the metabolism of nitroxides by subcellular organelles, we have chosen to study the metabolism of 4-hydroxy 2,2,6,6-tetramethylpiperidine-N-oxyl in isolated rat liver microsomes. Microsomes were able to reduce Tempol slowly without any substrate addition; when NADPH was added, the reduction rate substantially increased. In phenobarbitone induced rats the reduction rate was significantly higher than in not-induced microsomes. NADPH-dependent reduction rate was inhibited by thallium chloride (an inhibitor of the flavin-centered cytochrome P-450 reductase), superoxide dismutase, and by N-ethylmaleimide; menadione increased it. The Tempol reduction rate was not significantly affected by various cytochrome P-450 inhibitors with the sole exception of metyrapone. A solution containing purified cytochrome P-450 reductase and NADPH readily reduced Tempol. Microsomes fortified with NADPH were able to reduce Tempol at an appreciable rate. In order to distinguish between reduction of nitroxides to hydroxylamine or destruction of nitroxides following nitroxide reduction, microsomal suspensions were treated with a mild oxidant (ferricyanide 0.5-10 mM). The recovery varied from 40 to 60%, indicating a process of probe destruction leading to as yet unknown metabolites. The present study clearly indicates that, in this model system, cytochrome c (P-450) reductase and not cytochrome P-450 is responsible for the observed Tempol metabolism; along with hydroxylamine formation, other Tempol derived metabolites are formed during the process.

Cardiovascular involvement in relapsing polychondritis.

Relapsing polychondritis is an inflammatory disease that characteristically involves cartilagenous tissues. Cardiovascular involvement is a fairly common complication and the second most frequent cause of mortality in this disease. The case of a man with a progressive cardiac involvement, aortic incompetence, mitral regurgitation, and finally complete atrioventricular block offered the opportunity of reviewing the cardiovascular complications in relapsing polychondritis. The most frequent abnormalities are aortic regurgitation and aortic aneurysm. Furthermore, several cases of atrioventricular block, mitral regurgitation, and acute pericarditis have been reported. For early diagnosis and treatment of these severe complications, periodic cardiovascular examination is mandatory in these patients.

Mortality among drug users in the AIDS era.

BACKGROUND: Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. METHODS: All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. RESULTS: There were 332 deaths among 4962 drug users who were followed for 21,130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. CONCLUSIONS: Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients.

Intermittent heparin treatment does not induce hypercoagulability in haemodialysed patients.

Antithrombin-III (AT-III) and factor VIII coagulant (F VIII:C) and antigenic (F VIII:RA) activities have been studied in nine conservatively treated and 26 dialysed uraemic patients. AT-III levels were not significantly different from those of controls in either group. Among dialysed patients, those who had experienced thrombotic occlusions of the vascular accesses could not be distinguished from the remaining patients on the basis of their AT-III levels. Both F VIII:C and F VIII:RA were slightly higher than in controls in conservatively treated patients, but significantly higher in haemodialysed patients, especially in those who had never experienced thrombotic complications of the vascular accesses. No acute changes were observed in either the AT-III or F VIII:C/F VIII:RA ratio in five patients given heparin therapy during a dialytic session or in the interdialytic period. Thus repeated intermittent heparin treatment does not induce a hypercoagulable state in haemodialysed patients.

Adrenocorticotropin normalizes the blood levels of nitric oxide in hemorrhage-shocked rats.

Anesthetized rats were subjected to volume-controlled hemorrhagic shock by stepwise bleeding. Besides cardiovascular and respiratory functions, nitric oxide (NO)-hemoglobin formation in arterial blood was directly evaluated by means of electron spin resonance spectroscopy. During hemorrhagic shock there was a massive increase in NO-hemoglobin, associated with a fall in mean arterial pressure, pulse pressure, respiratory rate and heart rate, and there was a further increase in NO-hemoglobin 15 min after intravenous (i.v.) treatment with saline. All rats died within 30 min. The reversal of the shock condition induced by the i.v. injection of the adrenocorticotropin (ACTH) fragment 1-24 (160 microg/kg, 5 min after bleeding termination) was associated with a prompt disappearance of NO-hemoglobin. Also S-methylisothiourea (3 mg/kg i.v.), a selective inhibitor of inducible NO synthase, provoked a disappearance of NO-hemoglobin and reversal of the shock condition. The present results provide a direct demonstration that volume-controlled hemorrhagic shock is associated with highly increased blood levels of NO, as indicated by increased NO-hemoglobin, and indicate that ACTH-induced reversal of the shock condition is associated with the normalization of NO blood levels, and a parallel improvement of cardiovascular and respiratory functions. This occurs probably through the inhibition of inducible NO synthase, as suggested by the fact that S-methylisothiourea, a selective inhibitor of this NO synthase isoform, produced the same results.