Evaluation of patient-reported outcomes data in structured diabetes education intervention: 2-year follow-up data of patient empowerment programme.

To examine the effects of a structured group-based education programme, patient empowerment programme (PEP), compared with usual care on 2-year changes in patient-reported outcomes (PRO) in patients with diabetes mellitus (DM). A prospective observational study of 715 patients (PEP/non-PEP: 390/325) was conducted to complete the baseline PRO survey and followed up for 2 years. Health-related quality of life (HRQOL) was measured using the short-form 12 at baseline and annually at two follow-up assessments, which yielded physical and mental component summary and SF-6D preference-based scores. Perceived control over diabetes and general health status were measured using the patient enablement instrument (PEI) and global rating scale (GRS) at follow-ups. When compared with non-PEP, PEP participants significantly reported improvement in health condition (GRS score > 0; 24.55 % vs 10.16 %; odds ratio = 2.502; P = 0.018) in 2 years and enabled the self-perceived control over diabetes (PEI score > 0; 72.20 % vs 38.40 %; odds ratio = 3.25; P < 0.001) in 1-year follow-up but no sustained effects in year 2 (52.65 % vs 39.04 %; odds ratio = 1.366; P = 0.265). There were no significant differences between PEP and non-PEP groups in the changes in quality of life scores (all P > 0.05) at 1 year. Although HRQOL scores deteriorated over 2-year period in both groups, PEP participants reported similar changes in HRQOL scores to that of non-PEP. PEP for DM patients preserved self-perceived disease control and health condition, whereas PEP participants perceived their HRQOL similar to that of non-PEP participants. Findings of PRO should be considered alongside clinical outcomes when evaluating the overall benefits of PEP.

First Report of Leaf Spot Caused by Cercospora fukushiana on New Guinea Impatiens in Korea.

New Guinea impatiens, Impatiens hawkeri W. Bull, is widely cultivated as a potted plant and garden plant. In July 2013, hundreds of young plants (cv. Fanfare) showing symptoms of leaf spot with approximately 50% incidence were found in polyethylene tunnels in Yongin City, Korea. Leaf spots were circular to oblong, reaching 6 mm or more in diameter. The spots were initially uniformly brown to reddish brown, turning gray with reddish brown margin. Diseased plants defoliated prematurely and were abandoned without marketing due to signs of discoloration and yellowing on leaves. A cercosporoid fungus was consistently observed in association with disease symptoms. Stromata were brown, small, and composed of a few swollen hyphal cells. Conidiophores were emerging through the cuticle, fasciculate (n = 2 to 20), olivaceous to brown, paler toward the apex, straight to mildly curved, geniculate, 30 to 260 µm long, 3.5 to 5 µm wide, 1- to 6-septate, and with conspicuous conidial scars. Conidia were hyaline and acicular. Smaller conidia were straight and longer conidia were mildly curved. Conidia were subacute to obtuse at the apex, truncate to obconically truncate at the base, 2- to 18-septate, 30 to 320 × 3.5 to 5.5 µm, and with thickened, darkened hila at the base. Morphological characteristics of the fungus were consistent with the previous reports of Cercospora fukushiana (Matsuura) W. Yamam. (1). Voucher specimens were housed in the Korea University herbarium (KUS). An isolate from KUS-F27438 was deposited in the Korean Agricultural Culture Collection (Accession No. KACC47640). Fungal DNA was extracted with DNeasy Plant Mini Kits (Qiagen Inc., Valencia, CA). The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 (4) and sequenced. The resulting sequence of 497 bp was deposited in GenBank (Accession No. KJ620981). This showed >99% similarity with sequence of C. fukushiana (EF600954) on I. balsamina from Korea. Isolate of KACC47640 was used in the pathogenicity tests. Hyphal suspensions were prepared by grinding 3-week-old colonies grown on PDA with distilled water using a mortar and pestle. Five plants were inoculated with hyphal suspensions and five plants were sprayed with sterile distilled water. The plants were covered with plastic bags to maintain a relative humidity of 100% for 24 h and then transferred to a 25 ± 2°C greenhouse with a 12-h photoperiod. Typical symptoms of necrotic spots appeared on the inoculated leaves 10 days after inoculation, and were identical to the symptoms observed in the field. C. fukushiana was re-isolated from symptomatic leaf tissues, confirming Koch's postulates. No symptoms were observed on water-inoculated control plants. Previously, leaf spots of Impatiens spp. associated with C. apii, C. balsaminae, and C. fukushiana have been reported (1,2,3). To our knowledge, this is the first report of C. fukushiana on I. hawkeri in Korea. Our observations in the nurseries of I. hawkeri suggest that low humidity with good ventilation as well as plant hygiene in greenhouses might be main strategies for preventing this disease. References: (1) C. Chupp. A Monograph of the Fungus Genus Cercospora. Ithaca, NY, 1953. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., online publication, ARS, USDA, retrieved March 25, 2014. (3) J. M. Soares et al. Plant Dis. 93:1214, 2009. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.

Bidirectional transbilayer movement of phospholipid analogs in human red blood cells. Evidence for an ATP-dependent and protein-mediated process.

The transbilayer movement of fluorescent and isotopically labeled analogs of phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) from the outer to the inner leaflet (flip) and from the inner to the outer leaflet (flop) of human red blood cells (RBC) was examined. The inward movement of 1-oleoyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole-aminocaproyl)- (C6-NBD-), 1-oleoyl-2-(N-(3-(3-[125I]iodo-4-hydroxyphenyl)propionyl)aminocaproyl)- (C6-125I-), or 1-oleoyl-2-(N-(3-3-[125I]iodo-4-azido-phenyl)propionyl)aminocaproyl- (C6-125I-N3-) analogs of PC and PE were relatively slow. In contrast, all analogs of PS and PE analogs containing aminododecanoic acid (C12 lipids) were rapidly transported to the cell's inner leaflet. Analysis of 125I-N3 lipids cross-linked to membrane proteins revealed labeling of 32-kDa Rh polypeptides that was dependent on the lipid's capacity to be transported to the inner leaflet but was independent of lipid species. To investigate whether lipids could also be transported from the inner to the outer leaflet, lipid probes residing exclusively in the inner leaflet were monitored for their appearance in the outer leaflet. Lipid movement could not be detected at 0 degrees C. At 37 degrees C, however, approximately 70% of the PC, 40% of the PE, and 15% of the PS redistributed to the cells outer leaflet, thereby attaining their normal asymmetric distribution. Continuous incubation in the presence of bovine serum albumin depleted the cells of the analogs (t1/2 approximately 1.5 h) in a manner that was independent of lipid species. Similar to the inward movement of aminophospholipids, the outward movement of PC, PE, and PS was ATP-dependent and could be blocked by oxidation of membrane sulfhydryls and by the histidine reagent bromophenacyl bromide. Evidence is presented which suggests that the outward movement of lipids is an intrinsic property of the cells unrelated to compensatory mechanisms due to an imbalance in lipid distribution.

Induction of cerebroside synthesis in oligodendroglia.

Oligodendroglia function to produce myelin membranes which surround axons, enhancing saltatory conduction. Myelin consists of a multitude of condensed membranes which are rich in lipids with the major glycolipids, cerebrosides, being 25% of the total lipid. Thus a fully differentiated oligodendroglial cell that is producing myelin membranes would be actively synthesizing cerebrosides. Our laboratory has prepared and analyzed oligodendroglia from mature bovine brain, from neonatal rat brain, and from actively myelinating rat brain. Our studies suggest that the rat oligodendroglia in our culture systems are less differentiated than bovine cells in that they produce lower levels of cerebrosides. Addition of glucocorticoids, thyroid hormone, or retinoic acid all increased synthesis of cerebrosides in rat oligodendroglia. Ketone bodies were also somewhat stimulatory. Having no effect or causing dedifferentiation of the cells were 5-azacytidine and phorbol esters. Thus induction of cerebroside synthesis in oligodendroglia is complex and may involve many factors.

Hydrocortisone induction during oligodendroglial differentiation.

Steroid hormones are important for the normal development of brain. The addition of hydrocortisone to oligodendroglia in culture increases the level of mRNA for proteolipid protein, increases the synthesis of cerebrosides, and provides an induction of activities for the ketone body metabolizing enzymes. While proteolipid protein and cerebrosides are major components of myelin membranes, ketone bodies serve as precursors for lipid synthesis during development. Thus, hydrocortisone is important during the differentiation of oligodendroglia and during initial myelin production.

The effects of nifedipine and captopril on renal function in patients with essential hypertension: comparison with sodium nitroprusside.

In comparison with a nonspecific vasodilator, sodium nitroprusside (SNP), we intended to deduce the characteristics of nifedipine (NIF) and captopril (CAP) in the treatment of hypertension. Ten patients with essential hypertension were hospitalized and kept on a constant sodium diet (10 g NaCl/day). Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured before and after the respective administration of SNP (0.9 +/- 0.5 mcg/kg/min), NIF (17 +/- 5 mg), and CAP (85 +/- 24 mg). SNP significantly reduced the mean blood pressure (MBP), the renal vascular resistance index (RVRI), urine volume (UV), urinary excretion of sodium (UNaV), and significantly raised active renin concentration (ARC), plasma norepinephrine (NE), and the heart rate (HR). RBF, GFR, and plasma epinephrine (E) were not changed. Compared with SNP, NIF significantly raised RBF, UV, UNaV, and fractional excretion of sodium (FENa) and significantly reduced RVRI. The differences between the increases in ARC, NE, and HR by NIF and those by SNP were not significant. GFR and E were not changed by NIF. Although CAP did not reduce MBP as much as SNP did, the increase in RBF by CAP was significantly greater than that by SNP. Changes in GFR, UV, UNaV, FENa, and E by CAP were not different than those by SNP. CAP increased ARC and did not raise E, NE, and HR. In conclusion, compared with SNP, NIF significantly raised RBF, UV, UNaV, and FENa and significantly reduced RVRI. On the other hand, the renal response to CAP was not very much different from the response to SNP. The characteristics of CAP were the suppressed sympathetic response to the decrease in blood pressure.

Prevention of nephrosclerosis and cardiac hypertrophy by captopril treatment of spontaneously hypertensive rats.

The relationship between hypertension and cardiovascular damage was assessed in three groups of spontaneously hypertensive rats (SHR): 1. stroke prone SHR (SHR-SP) treated orally with an angiotensin I converting enzyme inhibitor (captopril) (100-400 mg/L in the drinking water) from 6 to 35 weeks of age, 2. SHR-SP maintained on tap water until 30 weeks of age, 3. stroke resistant SHR (SHR-SR) maintained on tap water. The controls were Wister Kyoto rats (WKY) maintained on tap water. Captopril-treated SHR-SP showed blood pressure lower than that of untreated SHR-SP, similar to SHR-SR. The ratio of heart weight to body weight was 0.55% in SHR-SP, 0.39% in captopril-treated SHR-SP, 0.46% in SHR-SR, and 0.39% in WKY. The kidneys of SHR-SP showed glomerular sclerosis, glomerular fibrosis, tubular casts, interstitial cell infiltration and vascular wall thickening or hyperplasia of the small arteries and arterioles. The severe glomerular sclerosis was mostly distributed in the inner and middle portions of cortex. Immunohistological study showed IgG, C3 and fibrinogen in the glomeruli and arterioles in SHR-SP. In captopril-treated SHR-SP, similar to SHR-SR, only minor histological changes were seen and there was no deposition of IgG, C3 or fibrinogen. No changes were seen in WKY. Thus, it was concluded that nephrosclerosis and cardiac hypertrophy in SHR-SP are prevented by captopril. The role of the renin-angiotensin and kallikrein-kinin systems in organ pathogenesis in SHR-SP is discussed.

Dynamic changes in plasma inactive renin levels in Bartter's syndrome after administration of captopril and angiotensin II.

Changes in plasma active and inactive renin concentration (ARC and IRC) after captopril administration and angiotensin II (AII) infusion were studied in six patients with Bartter's syndrome. A single oral dose of captopril (8-25 mg) lowered the blood pressure and increased both ARC and IRC. AII infusion elevated blood pressure, suppressed ARC and increased IRC. In this syndrome of high renin levels, infused AII appeared to increase inactive renin secretion by reducing its conversion to active renin. On the other hand, an acute fall in AII levels and/or renal perfusion pressure by captopril increased both active and inactive renin. This indicates that the increase in the secretion of inactive renin, stimulated by captopril, might exceed any increase in its conversion to active renin in patients with Bartter's syndrome, in whom the production of renin is accelerated, and conversion of inactive renin to active renin probably already operates near its maximum.

Effects of enalapril maleate (MK-421) on renovascular hypertension.

The effects of enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied on 5 patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The therapeutic dosage was increased when the blood pressure (BP) was not controlled for more than 3 days. Blood sampling was performed before, and 5 hr and 24 hr after the first administration, and on the 3rd day with each dosage. The BP was normalized on 5 mg/day in 1 case, 10 mg in 1 case, 20 mg in 2 cases, and 40 mg plus mefruside in 1 case. Plasma renin activity (PRA) was significantly increased after 5 hr and recovered after 24 hr with 2.5 mg of the enalapril maleate, when the BP was not affected. This indicates that the increase in PRA is likely due to the reduced negative feedback of angiotensin II. When the blood pressure was lowered, PRA was increased and plasma aldosterone concentration (PAC) was decreased significantly. This rise of PRA may depend not only on the reduced negative feedback but also on the fall of BP. It is also considered that the PAC was decreased through the decrease in plasma angiotensin II. A fall of the glomerular filtration rate in one case and also a fall of the perfusion of the kidney of the stenotic side in another case were observed by radioisotope renograms. MK-421 administration was a useful treatment for RVH, and clearly normalized the BP of all the patients studied. However, there was a risk of a fall of renal function on the stenotic side due to the decrease in perfusion pressure.

[Dietetic aspects of preventing urolithiasis in patients with gout and uric acid diathesis]. / Dieticheskie aspeky profilaktiki mochekamennoi bolezni u bol'nykh podagroi i mochekislym diatezom.

Patients suffering from gout and uric acid diathesis received a specialized diet containing 70 g protein (85% of plant protein including 20 g of soybean protein isolate), 85 g fat and 350 g carbohydrates. As a result there was an improvement of the general well-being during dietetic management, a rise of pH of the urine to normal, a decrease in the concentration of uric acid in blood serum and urine with a simultaneous elevation of the latter's clearance, an increase in glomerular filtration, a reduction in blood cholesterol content. The data obtained allow the conclusion to be made about the necessity of the rigid observance of the diet by the patients. This will play an important role both in the treatment and prophylaxis of urolithiasis in the patients' population under consideration.

Production and release of inactive renin by human vascular smooth muscle cells.

Human arterial smooth muscle cells were obtained from surgically excised tissues and cultured by the explant method. The cultured cells had both active and inactive forms of an angiotensin I forming enzyme. About a five-fold increase in the activity was obtained by trypsin treatment. This renin-like enzyme was also found in abundance in the culture media, mostly in an inactive form. Most of the enzyme activity, either before or after the activation, was suppressed by an antibody specific to human renin. The inactive enzyme was activated to some extent also by acidification and by cold exposure. The molecular weight of the inactive enzyme was estimated to be approximately 49,000 by gel filtration. These results suggest that human vascular smooth muscle cells can produce renin and release an inactive form of renin, and can be a potential source of plasma inactive renin under certain conditions such as the anephric state.

Effects of enalapril maleate on plasma level of inactive renin in renovascular hypertension.

Changes in plasma levels of active and inactive renin after the treatment with enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied in five patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The dosage was increased when the blood pressure (BP) was not normalized for more than 3 days. Blood sampling was performed before, and 5 hours and 24 hours after the first administration, and on the 3rd day with each dosage. Active and inactive renin concentrations (ARC and IRC) showed a reciprocal change in 4 cases, 5 hours after the first dose. In the chronic treatment, ARC and IRC before the morning dose did not change apparently until the BP was normalized, when both ARC and IRC were evidently increased. It was suspected that a conversion from inactive to active renin may occur in the patients with RVH, when the active renin secretion is stimulated suddenly by the first dose of MK-421. The chronically diminished perfusion pressure in the kidney may stimulate the secretion of inactive renin, but the decrease in endogenous angiotensin II may not.

Successful treatment of the crisis of scleroderma with enalapril maleate (MK-421).

A 74-year-old man has been known to have scleroderma for 5 years. Two months before the hospitalization, his blood pressure was rapidly elevated, and progressive renal impairment and ulcerations of the fingers manifested. Then he was diagnosed to have a crisis of scleroderma. The treatment with a new long-acting angiotensin I converting enzyme inhibitor, enalapril maleate (MK-421), normalized the blood pressure and protected the progress of renal impairment without side effects.

High level of plasma inactive renin in Bartter's syndrome.

In 10 cases of Bartter's syndrome, plasma active and inactive renin (AR and IR) were measured by two different methods. First, plasma renin activity (PRA), and total renin activity (TRA) after activating IR with trypsin, were measured by radioimmunoassay (RIA) of angiotensin I (AI) generated from endogenous substrate. And secondly, plasma active renin concentration (ARC) and total renin concentration (TRC) were measured by RIA of AI generated in the presence of an excess of exogenous substrate. The difference between TRA and PRA, and between TRC and ARC were designated as inactive renin activity (IRA) and inactive renin concentration (IRC), respectively. Small amounts of IRA were found only in 2 cases and no IRA in 8 cases. However, the existence of large amounts of IR in Bartter's syndrome was revealed by the IRC determination. This suggests that the shortage of endogenous renin substrate, consumed by the markedly increased AR, may have interfered with the detection of IRA in Bartter's syndrome, though the IR is markedly increased as well. The molecular weights of AR and IR were determined by Sephadex G-100 gel filtration in 3 cases. Both AR and IR seemed to be smaller than those of normal subjects.

Angiotensin II analogue infusion test in renovascular hypertension under low sodium intake and under spironolactone administration: is angiotensin II analogue infusion test useful in determining the mode of treatment?

An angiotensin II antagonist (1-Sar, 8-Ileu-angiotensin II) was infused into 5 hypertensive patients with unilateral renal artery stenosis under 5-day low sodium diet (2 g NaCl/day) and under 7-day spironolactone administration (300 mg/day). In the sodium depleted state, 1 case showed depressor response, 2 cases pressor response and the other 2 no response. During the spironolactone administration, 3 cases showed depressor, 1 case pressor, and another case no response. Angiotensin II analogue (A II A) infusion test under spironolactone administration was more effective than under sodium depletion. However, there were cases which showed pressor response, i.e. false negative, under low sodium diet and under spironolactone administration. The hypertension of these patients was cured by converting enzyme inhibitor, percutaneous transluminal renal angioplasty (PTRA) or bypass surgery. A II A infusion test has been used for screening, diagnosis and determination of the surgical repair of renovascular hypertension. However, the proportion of depressor response was low in our cases, yet pressor responders and non-responders were also cured by PTRA. PTRA is a painless and low risk procedure of the treatment of renovascular hypertension, so PTRA will become the preferential mode of therapy for the treatment of renovascular hypertension of the cases with no depressor response by AIIA infusion.

Studies on the active and inactive renin in renovascular hypertension.

Active and inactive plasma renin concentrations (ARC and IRC) from both renal veins and the femoral artery, and the molecular weight (MW) of active and inactive renin (AR and IR) from both renal veins were measured in 6 patients with renovascular hypertension due to unilateral renal artery stenosis. Venous ARC on the affected side was higher than that on the unaffected side and arterial ARC. In 4 patients ARC increased and IRC decreased after circulating through the stenotic kidney, while in the other 2 cases venous IRC on the stenotic side was higher than arterial IRC. The MW of AR on the stenotic and non-stenotic sides were 40000-48000 and 45000-48000, respectively, and those of IR varied from 45000-53000 and 48000-55000, respectively. These values seem to be smaller than those of normal subjects. The renin molecule may be small immediately after the release from the kidney and become larger in the circulation. In 3 cases, whose ARC increased and IRC decreased after passing through the stenotic kidney, AR and IR from the stenotic kidney were smaller than those from the non-stenotic kidney. Some mechanism of AR and IR molecule reduction may work in the stenotic kidney to activate IR.

A case of 17 alpha-hydroxylase deficiency syndrome associated with right adrenal tumor.

A 35-year-old woman, who had been hypertensive for about 17 years and had lacked menarche, showed hypokalemia, low plasma cortisol and aldosterone levels, suppressed renin activity, and marked elevation of plasma corticosterone. The patient was diagnosed as having 17 alpha-hydroxylase deficiency from functional studies. In addition, a right adrenal tumor was found by adrenal venography. Adrenal venous sampling showed that this tumor might be secreting corticosterone and possibly also deoxycorticosterone (DOC). The genotype was 46,XY, so she was diagnosed as having male pseudohermaphroditism. Right adrenalectomy and contralateral adrenal biopsy were done. The retained testicles were removed. Dexamethasone administration normalized the blood pressure and serum potassium. This is the first report of 17 alpha-hydroxylase deficiency with a right adrenal tumor.

Synchronous changes in active and inactive renin secretion after furosemide in patients with primary aldosteronism.

Changes in plasma active and inactive renin concentrations (ARC and IRC) were measured in 10 patients with primary aldosteronism (PA) due to adrenal adenomas. Before the resection of adrenal adenomas, venous blood samples were taken at supine resting state, after 1-hour standing and 30 min. after furosemide injection and these samplings were repeated after surgical treatment. Plasma inactive renin was measured after activation with trypsin. Before the treatment ARC and IRC did not change by standing or furosemide. After the treatment, however, ARC was increased clearly by standing or furosemide, and IRC was also increased by furosemide injection. Both ARC and IRC at supine resting state were increased after the surgery. When the renin-angiotensin system is suppressed chronically by the over-produced aldosterone in patients with PA, not only active but also inactive renin secretions are suppressed, and fail to respond to orthostasis or furosemide. The secretion of IR could be stimulated after the removal of aldosteronoma.