A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation.

BACKGROUND: Exhaled nitric oxide (ENO) has been proposed as a noninvasive marker of airway inflammation in asthma. OBJECTIVE: We investigated the relationships among ENO, eosinophilic airway inflammation as measured by induced sputum, and physiologic parameters of disease severity (spirometry and methacholine PC(20)). We also examined the effect of corticosteroid treatment and atopy on ENO levels and eosinophil counts in induced sputum. METHODS: Measurements were taken on one day in 22 healthy nonatopic subjects, 28 healthy atopic subjects, 38 asthmatic subjects not taking inhaled steroids, 35 asthmatic subjects taking inhaled steroids, and 8 subjects with eosinophilic bronchitis without asthma. RESULTS: ENO levels showed significant but weak correlations with eosinophil differential counts in the steroid-naive asthmatic and healthy atopic groups (r (s) < 0.05). ENO levels were significantly lower in the asthmatic subjects taking steroids compared with the asthmatic subjects not taking steroids, despite there being no difference in the sputum cell counts, and a tendency to increased airflow limitation. ENO levels and sputum eosinophil counts were equally good at differentiating from steroid-naive asthmatic subjects. ENO levels were consistently raised in subjects with eosinophilic bronchitis without asthma. Atopy had no effect on ENO levels in the healthy subjects. CONCLUSION: We conclude that ENO is likely to have limited utility as a surrogate clinical measurement for either the presence or severity of eosinophilic airway inflammation, except in steroid-naive subjects.

Dermal angiopathy in hemodialysis patients: the effect of time.

We studied skin biopsies from 14 patients after 6 months to 18 years on hemodialysis (HD) to discern any effect of duration of treatment on skin and dermal capillaries. Patients selected for biopsy were without evidence of other diseases known to affect vasculature such as diabetes mellitus. Pathological changes compared with duration of HD were: capillary wall thickening, endothelial proliferation and new capillary formation, lipid content, and epidermal atrophy. Severity of morphologic changes were graded from 0 to 4+ by a pathologist who had no knowledge of HD duration. The earliest change observed was reduplication of the capillary basement membrane. Narrowing of capillary lumina due to endothelial cell proliferation and new capillary formation were noted after five years of HD; lipid droplets were noted in capillaries by five years; and epidermal atrophy by 10 years. Progressive severity of each finding was associated with length of time on HD. Neither amyloid nor Ca++ deposits were observed in any specimens. By clinical observation, easy bruisability and increased skin fragility were worse the longer the patient was on HD. Capillary occlusion inducing tissue ischemia could be a cause of the atrophic skin changes noted. However, no patient manifested dermal necrosis. While pathogenesis of the capillary changes in uremic skin is unknown, the changes have been shown to stabilize following successful kidney transplantation.

Carbamylated hemoglobin in prerenal azotemia.

UNLABELLED: Carbamylated hemoglobin (Carb Hb) levels were measured in 16 patients with a documented transient rise in BUN due to prerenal azotemia, in whom BUN levels before and after the episode were normal. They were compared with 13 controls. Carb Hb was expressed as carbamyl valine concentrations, which were significantly higher in the patients (166 micrograms/g Hb) than in controls (95.3 micrograms/g Hb, p < 0.01). The mean maximum BUN level in the patients was 51.8 +/- 23.9 mg/dl. There was a significant correlation between the product of mean BUN level times the number of days of BUN elevation, and the Carb Hb level (r = 0.5197; p < 0.05). There was no correlation between Carb Hb and either mean BUN level or maximum BUN level. Elevated Carb Hb was seen after a minimum of 4 days' BUN elevation. Four patients had no elevation of Carb Hb despite elevated BUN levels. CONCLUSION: Carb Hb may be elevated after a minimum of 4 days' transient BUN elevation; Carb Hb is not useful in differentiating between mild acute renal failure and prerenal azotemia.

The effect of aluminum on the vanadium-mediated oxidation of NADH.

Aluminum catalyzes the oxidation of NADH by vanadate both in the presence and absence of a reducing sugar. The effect of aluminum is concentration dependent and inhibitable with superoxide dismutase but not catalase. The fructose-6-phosphate-free reaction is characterized by an initial lag phase which can be eliminated by preincubating aluminum with NADH, but is not altered by preincubating aluminum with vanadate, suggesting that the effect of aluminum is not directly on vanadate. Aluminum also catalyzes vanadyl-mediated oxidation of NADH, and this effect is similarly inhibitable by superoxide dismutase as well as catalase. It is suggested that aluminum catalyzes the oxidation of NADH by vanadium though enhancing the production of superoxide radicals and that this effect may account in part of the biological toxicity associated with aluminum, particularly when associated with the accumulation of other trace elements such as vanadium.

Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL).

Blood flow rate and access recirculation in hemodialysis.

We studied the effect of extracorporeal blood flow rate (BFR) on access recirculation (recirc) in 19 hemodialysis patients. BUN was determined in simultaneous peripheral (P), arterial (A), and venous (V) blood obtained at BFRs of 200, 400, and 600 ml/min. Percent recirc was calculated for each BFR using the formula (P-A)/(P-V) x 100. Venous drip-chamber (VP) and pre-blood-pump (AP) pressures were measured at each BFR. Fistulograms were performed in 10 patients, and stenoses were identified in 5, all at the proximal (arterial) end of the access. Recirc increased with increasing BFR from 200 to 400 ml/min but increased little from 400 to 600 ml/min. At all BFRs recirc in the stenotic patients was higher than that of non-stenotic or unstudied patients. Urea clearance, corrected for recirc, rose with blood flow both in stenotic and non-stenotic patients. There were no differences in AP or in VP between stenotic and non-stenotic patients. At BFR greater than or equal to 400 ml/min, a recirc threshold of 15% identified stenoses with sensitivity 100% and specificity 71%. We conclude (1) recirc increases with increasing BFR but not enough to outweight the concomitant increase in urea clearance; (2) significant access stenosis and recirc may be present even with low VP; (3) recirc was associated with arterial side stenoses; (4) at BFR greater than or equal to 400 ml/min, access stenosis is associated with recirc greater than 15%.

Seroprevalence of antibodies to the human immunodeficiency virus in dialysis workers: results of a multi-center study.

The Center for Devices and Radiological Health, in collaboration with the Department of Veterans Affairs Medical Center, Brooklyn, N.Y., conducted a multi-center, multi-institutional study of the seroprevalence of antibodies to the human immunodeficiency virus (HIV) among dialysis workers. Seven dialysis units and 112 dialysis workers participated in the study over a period of 2 years. Participation was limited to dialysis workers who, by questionnaire, denied non-occupational risk factors for HIV infection. The vast majority of the study participants were drawn from areas where the prevalence of HIV infection and AIDS cases are substantially greater than the national average. Study participants received the ELISA test for HIV antibodies. All 112 of the participants tested negative for HIV antibodies. These results are encouraging, as they failed to reveal unrecognized occupational transmission of HIV infection among dialysis workers.

Effect of chromium on oxygen free radical metabolism, inhibition of superoxide dismutase and enhancement of 6-hydroxydopamine oxidation.

The effect of chromium on superoxide dismutase activity (SOD) as well as on the rate of hydroxydopamine oxidation was studied in vitro, since chromium is known as an environmental and occupational carcinogen and oxygen free radicals are implicated in carcinogenic processes. Chromium is a strong inhibitor of SOD activity in this system. The degree of inhibition is directly proportional to the chromium concentration (tested chromium range 0.166-0.33 mg/L in reaction mixture), to reaction time (tested range up to 10 minutes), and to substrate concentration. Autoxidation of 6-hydroxydopamine was increased by chromium concentration of 15 mg/L. The combination of excessive oxygen free radical production and inhibition of their elimination by inhibition of SOD activity may contribute to the toxic effects of chromium.

Acute phase protein, serum amyloid A, inhibits IL-1- and TNF-induced fever and hypothalamic PGE2 in mice.

The effect of serum amyloid A (SAA) on fever induced by recombinant interleukin-1 beta (rIL-1 beta) or recombinant tumour necrosis factor alpha (rTNF alpha) was studied in mice. Serum amyloid A is an acute phase protein whose rise in pathological events is induced by the cytokines IL-1, IL-6 and TNF. Administration of human serum amyloid A to mice inhibited fever induced by rIL-1 beta or rTNF alpha in vivo, while the addition of human serum amyloid A to mice hypothalamic slices inhibited IL-1 beta- or TNF alpha-induced prostaglandin E2 (PGE2) production in vitro. Since serum amyloid A did not affect body temperature or hypothalamic PGE2 levels when administered alone, it may represent a specific servo-mechanism for fever regulation in acute events, and it suggests, for the first time, a possible feedback relationship between serum amyloid A and the immunoregulatory cytokines.

Effect of nickel on oxygen free radical metabolism. Inhibition of superoxide dismutase and enhancement of hydroxydopamine autoxidation.

The effect of nickel on superoxide dismutase activity (SOD), as well as on rate of hydroxydopamine oxidation, was studied in vitro since lipid peroxidation has been implicated in cell damage by nickel, whose toxicity and carcinogenicity are well established. Nickel strongly inhibits SOD activity. The degree of inhibition is directly proportion to the nickel concentration (tested range 0.066 to 0.33 microgram/mL in the reaction mixture); to the substrate concentration (tested range 0.4 x 10 4M to 1.1 x 10 4M 6-hydroxydopamine); and to reaction mixture. Autoxidation of 6-hydroxydopamine was increased by nickel concentrations higher than 15 micrograms/mL. The combination of excessive oxygen free radical production and inhibition of their elimination by inhibition of SOD activity may contribute to the nickel toxicity that has been reported in industrial accidents, as well as to the high incidence of cancer occurring in nickel workers. It may also contribute to many complications in uremic patients, in whom increased serum nickel levels were reported to be in a similar range to those inhibiting SOD.

Effect of aluminum on calcium binding to bovine intestinal calcium-binding protein.

Aluminum is known to inhibit vitamin D-dependent intestinal absorption of calcium. To investigate possible mechanisms of action, the effect of aluminum on the binding of calcium to bovine intestinal calcium-binding protein (CaBP) was studied by means of equilibrium dialysis. The results of these studies indicate that aluminum in concentrations up to 80 microM and up to 80 times the ambient calcium concentration did not significantly alter the affinity of CaBP for calcium (Kd = 0.17 microM) nor its molar capacity (2 mol/mol CaBP).