Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects

The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between -1.00 and -8.00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73.3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0.0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2.41 (SD) 1.91, compared with -0.66 (SD) 2.66 dB for the placebo group (unpaired Student's t test, P<0.0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0.05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia.     

Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Can azathioprine and steroids alter the progression of severe Henoch-Schönlein nephritis in children?

To evaluate the effect of azathioprine with steroids on the clinical course and histologic parameters of severe Henoch-Schönlein nephritis (HSN), 20 patients with a median age of 9.3 years (range 4.4–17 years) and a follow-up period of 4.8 years (range 1–14 years) were included in this study. The patients were divided into two groups. Ten patients received azathioprine with steroids for 8 months (group A), and the other ten received steroids alone (group B). All patients underwent renal biopsy at presentation, and ten of them who were treated with azathioprine underwent follow-up biopsy after therapy. Six patients in group A achieved clinical remission, and the remaining four showed minor urinary abnormalities at the latest observation. The histological grades of the International Study of Kidney Disease in Children (ISKDC) improved in four of the ten patients, and the activity index decreased significantly from 6.8±2.0 to 4.3±2.3 (p=0.016). In group B, however, four patients had normal urine and renal function; two had minor urinary abnormalities; one had active renal disease, and three had chronic renal insufficiency, at the latest observation. The combination treatment of azathioprine and steroids may be beneficial in ameliorating histopathological features and improving the clinical course of severe HSN.     

Posttraumatic vasospasm: the epidemiology, severity, and time course of an underestimated phenomenon: a prospective study performed in 299 patients

OBJECT: The purpose of this prospective study was to evaluate the cumulative incidence, duration, and time course of cerebral vasospasm after traumatic brain injury (TBI) in a cohort of 299 patients. METHODS: Transcranial Doppler (TCD) ultrasonography studies of blood flow velocity in the middle cerebral and basilar arteries (VMCA and VBA, respectively) were performed at regular intervals during the first 2 weeks posttrauma in association with 133Xe cerebral blood flow (CBF) measurements. According to current definitions of vasospasm, five different criteria were used to classify the patients: A (VMCA > 120 cm/second); B (VMCA > 120 cm/second and a Lindegaard ratio [LR] > 3); C (spasm index [SI] in the anterior circulation > 3.4); D (VBA > 90 cm/second); and E (SI in the posterior circulation > 2.5). Criteria C and E were considered to represent hemodynamically significant vasospasm. Mixed-effects spline models were used to analyze the data of multiple measurements with an inconsistent sampling rate. Overall 45.2% of the patients demonstrated at least one criterion for vasospasm. The patients in whom vasospasm developed were significantly younger and had lower Glasgow Coma Scale scores on admission. The normalized cumulative incidences were 36.9 and 36.2% for patients with Criteria A and B, respectively. Hemodynamically significant vasospasm in the anterior circulation (Criterion C) was found in 44.6% of the patients, whereas vasospasm in the BA-Criterion D or E-was found in only 19 and 22.5% of the patients, respectively. The most common day of onset for Criteria A, B, D, and E was postinjury Day 2. The highest risk of developing hemodynamically significant vasospasm in the anterior circulation was found on Day 3. The daily prevalence of vasospasm in patients in the intensive care unit was 30% from postinjury Day 2 to Day 13. Vasospasm resolved after a duration of 5 days in 50% of the patients with Criterion A or B and after a period of 3.5 days in 50% of those patients with Criterion D or E. Hemodynamically significant vasospasm in the anterior circulation resolved after 2.5 days in 50% of the patients. The time course of that vasospasm was primarily determined by a decrease in CBF. CONCLUSIONS: The incidence of vasospasm after TBI is similar to that following aneurysmal subarachnoid hemorrhage. Because vasospasm is a significant event in a high proportion of patients after severe head injury, close TCD and CBF monitoring is recommended for the treatment of such patients.     

Juvenile prostatic hyperplasia

Benign prostatic hyperplasia is common in aging men, but rare in childhood. We report a case of juvenile prostatic hyperplasia in a 10-year-old boy, who visited our clinic for hematuria and voiding symptoms. Radiologic studies revealed a huge prostate protruding into the bladder. The prostate was 33 g. The prostate biopsy showed no evidence of cancer. At 13 years of age, he was seen again because of general weakness, fever, and voiding difficulty. Bilateral hydroureteronephrosis was found on radiologic studies, and his serum creatinine was elevated. The prostate was 55 g. Suprapubic prostatectomy was performed.     

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

This study was conducted to determine if the long-term administration of the phosphodiesterase type 5 (PDE 5) inhibitor, DA-8159, to diabetic rats can ameliorate the development of erectile dysfunction (ED) and endothelial dysfunction. After inducing diabetes with streptozotocin, DA-8159 was orally administered at a dose of 3 mg/kg or 10 mg/kg for 8 weeks. To examine the effect on erectile response, electrostimulation of the cavernous nerve with the parameters of 3 V, 5 ms, 5 Hz or 10 Hz, was performed to measure the intracavernous pressure (ICP) and mean arterial pressure (MAP). Thoracic aorta relaxation in vitro was evaluated by adding acetylcholine (Ach) cumulatively to the bathing medium. In addition, the plasma endothelin-1 (ET-1) levels were measured in order to investigate the effect of DA-8159 on endothelial dysfunction. The area under the curve (AUC) from the ICP/MAP ratio in the 10 Hz stimulation showed a significantly increased AUC after the 10 mg/kg treatment compared with the diabetic group (8891 +/- 619 vs. 6316 +/- 1016, respectively, p < 0.05). At the 5 Hz frequency, DA-8159 10 mg/kg also induced a significant increase in the AUC compared with the diabetic control. The maximum ICP/MAP ratio (%) of the 10 mg/kg treatment group was significantly higher in both the 10 Hz and 5 Hz frequency groups (p < 0.05). A treatment of 3 mg/kg tended to increase the AUC and peak ICP/MAP but was not statistically significant. The Ach EC50 value of the diabetic group was significantly higher than in the normal control (120.50 +/- 22.90 nm vs. 86.80 +/- 9.30 nm, respectively), and 10 mg/kg treatment group showed a significantly lower EC(50) value (88.38 +/- 19.7 nm). The ET-1 level was lower in groups treated with DA-8159, 3 mg/kg and 10 mg/kg treatment induced a statistical difference compared with the diabetic control (1.15 +/- 0.34 fmol/mL vs. 2.51 +/- 0.55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function.     

Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome

The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P = 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n = 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P = 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.     

Facilitation of the purinergic contractile response of the guinea pig vas deferens by sodium orthovanadate

Experiments were carried out to examine the effects of protein tyrosine kinase (PTK) and protein tyrosine phosphatase inhibitors on the purinergic contraction of the guinea pig vas deferens. Sodium orthovanadate (SOV) produced a robust increase of the amplitude of contractions evoked by both neurogenic electrical field stimulation and exogenous ATP. This effect of SOV was concentration- and time-dependent, as well as, reversible and reproducible. Genistein, a PTK inhibitor, but not its inactive structural analog daidzein, inhibited the SOV-induced facilitation of the purinergic contraction. Another PTK inhibitor, 2,5-dihydroxycinnamic acid methyl ester, which is structurally unrelated to genistein, also inhibited the facilitation effects of SOV. Although an application of as low as 3 microM of these inhibitors significantly decreased the effect of SOV, other PTK inhibitors, namely, butein, levandustin C, and thyrphostin 23, were less effective even at concentrations of 100 microM. Western blot experiments showed that the facilitation of the purinergic contraction by SOV is associated with a prominent increase in the level of tyrosine phosphorylation of proteins with estimated molecular sizes of 180 and 123 kDa, which was reversed in the presence of genistein. Evidence is also presented that argue against the possibility that inhibition of the Na(+)/K(+)-ATPase or ATPases, responsible for the clearance of ATP is involved in the SOV-induced facilitation of the purinergic contraction. Together, these results suggest that the responsiveness of the smooth muscle of the vas deferens to the actions of ATP is modulated via a previously unidentified mechanism, which may involve protein tyrosine phosphorylation.     

Human prostatic acid phosphatases: II. A double--antibody radioimmunoassay.

A double-antibody radioimmunoassay method for prostate-specific acid phosphatase (PAP) is presented. Experimental details are outlined to assess the reproducibility and reliability of the method under assay conditions. The upper limit of the serum PAP levels in the present assay was set at 2.4 ng/100 microliter by 162 determinations of normal serum samples. The serum PAP levels of patients with nonprostatic malignant tumors fell in the normal range, whereas the levels higher than 4.0 ng/100 microliter were found in patients with prostatic carcinoma.