Utilization of common inflammatory markers in new, symptomatic, primary care outpatients based on their cost-effectiveness.

Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Clinical effect of LM-001, prostaglandin synthetic inhibitor, on pain from urinary tract stone and vesical urgency after operation of the bladder or prostate

Clinical effect of LM-001, a prostaglandin synthetic inhibitor developed from a drug delivery system, was evaluated in 54 patients with pain from urinary tract stones (stone pain) and 32 with vesical urgency after an operation on bladder or prostate. LM-001, felbinac ethyl incorporated in lipid microsphere, wes intravenously administered at the onset of stone pain or vesical urgency. Of 54 with stones and 32 with urgency, 53 and 29 were eligible for response, respectively. The symptoms improved or disappeared in some cases just after the administration and in the majority of patients within 15 minutes, in 49 of 53 patients with stone pain. Further, the effectiveness lasted over 24 hours in 26 of the 49 responding to this agent. On one hand, improvement or disappearance of vesical urgency was recognized in 25 of 29 patients, and the effectiveness was observed shortly after injection in 16 and lasted over 24 hours in 13 cases. Toxicities of this drug were investigated in 54 patients with stone pain and 32 with urinary urgency. Side effects consisted of pain at the injection site in 4, a slight fall of blood pressure in 1, slight visual disturbance in 1, body heat sensation in 1, leukocytosis in 3 and elevation of alkaline phosphatase in 1. These symptoms were transient and disappeared without use of any agent. LM-001 is concluded to be a useful drug for controlling stone pain and vesical urgency since an immediate effect, long durability and high response rates were obtained without severe side     

Auditory brainstem responses after out-of-hospital cardiac arrest: Are they useful for outcome prediction?

We evaluated whether we could predict the neurologic outcome in 55 out-of-hospital cardiac arrest patients using auditory brainstem responses (ABR). ABR patterns were classified into one of 3 types by evaluation of 5 components: type 1, with all 5 components; type 2, lack of at least one response between the 2nd and 5th components; type 3, with only the first component or no response. The relation between the ABR patterns on the 3rd day following resuscitation and the neurologic outcome on hospital discharge was evaluated. The specificity that the 5 awake patients had type-1 ABR was 38%. The sensitivity that the 10 brain dead patients had type-3 ABR was 60%. In the type-1 ABR patients, the negative predictive value that the patients were awake was 100%. In the type-3 ABR patients, the negative predictive value that the patients became brain dead was 90.9%. These results suggest that ABR on the 3rd post-resuscitation day may not be useful for predicting if patients are awake or become brain dead, although the loss of components may be a sign of morbidity, and the presence of the 2nd or later components indicates possible future prevention of brain death.     

Ocular hypotensive effects of monoamine oxidase-A inhibitors in rabbit

The effects of monoamine oxidase-A (MAO-A) inhibitors with epinephrine on intraocular pressure in the pigmented rabbit were studied. MAO-A inhibitors were used topically with or without various concentrations of epinephrine. For the measurement of intraocular pressure, applanation pneumatonography was used and tissue MAO activities were determined by radiometric assay. After topical administration with clorgyline, MAO-A activities in the bulbar conjunctiva and the iris-ciliary body were remarkably inhibited, whereas MAO-B inhibition was minimal. Maximal reduction of intraocular pressure with 0.05% epinephrine was 3.2 mmHg. Single administration of clorgyline, amiflamine, moclobemide or CGP 11305-A caused decreases in the intraocular pressure of 2.0, 2.5, 1.8 and 2.4 mmHg, respectively. In the coadministration experiments with epinephrine, the ocular hypotensive effects of epinephrine were potentiated with clorgyline, amiflamine, moclobemide and CGP 11305-A (6.6, 4.8, 5.6 and 5.8 mmHg). On the contrary, they were not influenced by the MAO-B inhibitor deprenyl. These results indicated that MAO-A inhibitors potentiated the ocular hypotensive effects of epinephrine, and that the coadministration of a reversible MAO-A inhibitor with epinephrine might be useful for patients with glaucoma.     

The effect of interleukin-1 on iron metabolism in rats

The effect of interleukin-1 on iron metabolism in rats was evaluated. Plasma iron decreased from 184 +/- 16 micrograms/dl (mean +/- SE) to 24 +/- 12 at 6 hours after interleukin-1 intramuscular administration in non-fasting rats and 109 +/- 6 micrograms/dl to 12 +/- 1 micrograms/dl in fasting rats, which was significantly lower than in control rats. Ferrokinetic studies showed a more rapid disappearance rate and lower iron turnover in interleukin-1-injected rats. The release of iron from the mononuclear phagocyte system to plasma was studied at 3 h after interleukin-1 administration. Although the percent of radioactivity in plasma of the total injected dose was 3.2 +/- 0.6% in interleukin-1, which was significantly lower than in the control rats (5.4 +/- 0.6%) at 9 h after intravenous injection of 59Fe chondroitin ferrous sulfate, there was no difference between the amount of 59Fe released from the mononuclear phagocyte system over the first 9 h in interleukin-1 and control rats. These data appear to imply that iron release is unimpaired but that, for some reason, there is an enhanced rate of clearance of the 59Fe once it has been released from the mononuclear phagocyte system into the plasma.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.     

Epithelium-dependent and -independent inhibitory effects of sivelestat, a neutrophil elastase inhibitor, on substance P-induced contraction of airway smooth muscle in lipopolysaccharide-treated guinea-pigs.

The underlying mechanism involved in the interaction between neutrophil elastase inhibitors and tachykinins has not been elucidated. In this study we have examined the effects of sivelestat, a neutrophil elastase inhibitor, on the in vitro responses of airways from lipopolysaccharide (LPS)-untreated or -treated guinea-pigs to substance P. Substance P (0.01-30 micromol/l) produced concentration-dependent contractions of both tracheal and bronchial ring preparations of LPS-untreated or -treated guinea-pigs. Responsiveness to substance P in these isolated airway preparations was augmented by either epithelium removal or LPS treatment. In epithelium-intact tracheal ring preparations isolated from LPS-untreated guinea-pigs, sivelestat (100 micromol/l) significantly inhibited substance P-induced contractions. The inhibitory action was markedly attenuated by pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l), and was almost undetected following removal of the epithelium. On the other hand, in bronchial ring preparations isolated from LPS-untreated guinea-pigs, sivelestat had only a very slight effect on substance P-induced contraction of the epithelium-intact preparation, whereas sivelestat greatly inhibited contraction in epithelium-removed bronchial ring preparations. In LPS-treated guinea-pigs, whether the epithelium was intact or not, sivelestat significantly inhibited the substance P-induced contraction of bronchial ring preparations. Pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l) did not affect the inhibitory effect of sivelestat in bronchial ring preparations. In conclusion, epithelium removal or LPS treatment induced hyperreactivity to substance P in the guinea-pig airway. Sivelestat caused epithelium-, nitric oxide- and prostaglandin-dependent inhibition of the substance P-induced contraction of isolated guinea-pig tracheal ring preparations. In contrast, the inhibitory effect of sivelestat on substance P-induced contraction of guinea-pig bronchial ring preparations is mediated by epithelium-, nitric oxide- and prostaglandin-independent mechanisms. Sivelestat may be effective in reducing the airway hyperresponsiveness to tachykinins induced by epithelial injury as occurs in LPS-mediated inflammatory lung diseases.     

An innovative method to measure skin pigmentation

Background/purpose: It is crucial to establish an accurate method for measuring skin pigmentation in cosmetic science and clinical dermatology. Here, we report a non-invasive precise method for measuring skin melanin content.
Methods: In order to determine the concentrations of melanin and hemoglobin in skin, we used the spectrum resolution (SR) method. In brief, the absorption spectrum of the skin was calculated from the reflection spectrum using a spectrophotometer. The concentrations of melanin and hemoglobin were then determined using a multiple regression analysis, assuming that the absorption spectrum of the skin is expressed as a linear summation of the absorptions of melanin and hemoglobin according to the Lambert–Beer law. The skin changes in the volar forearm, which had been irradiated by ultraviolet rays (UV), were observed daily by the SR method.
Results: A multiple regression analysis with an absorption spectrum of 500–700 nm was performed. The multiple correlation coefficient was 0.993, resulting in a satisfactory precise estimate of the concentrations of melanin. After UV irradiation, the concentration of melanin monitored by the SR method increased until 8 days and decreased gradually afterwards.
Conclusions: The SR method allows the evaluation of the changes of epidermal melanin induced by UV irradiation.