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Biomedical subjects

T Tikkanen

Publications and source records attributed to T Tikkanen.

At least 19 recordsLinked to original sources
PubMed2000

Predicting the outcome of invasive treatment of renal artery disease.

OBJECTIVE: Analysis of the factors influencing the outcome of performed or attempted invasive treatment for renal artery disease (RAD). SETTING: University Hospital. STUDY PATIENTS: Thirty-five hypertensive patients with 31 stenoses and 14 occlusions of renal artery. INTERVENTIONS: Angioplasty was performed on 25 patients (attempted for 30), primary stenting on one, nephrectomy on three, and renal resection on one patient. MAIN OUTCOME MEASURE: A decrease of diastolic blood pressure (DBP) by >/=15 mmHg after intervention. RESULTS: A DBP response was seen in 24 patients. In 11 patients, invasive treatment did not result in a DBP response or failed technically. Compared with these patients, the responders were younger (55 +/- 11 vs. 66 +/- 8 years, P = 0.001) and tended to have higher DBP (100 +/- 8 vs. 93 +/- 11 mmHg, P = 0.065). The function of the affected kidney, or that of the more affected kidney if RAD was bilateral, was better preserved in responders (relative clearance on captopril renography 23 +/- 15 vs. 8 +/- 4%, P = 0.008). A response was more often seen in unilateral than in bilateral RAD (81% vs. 33%, P = 0.015). A relative clearance of </=10% on captopril renography had sensitivity of 88% and specificity of 81% for renal artery occlusion. Step-wise logistic analysis. (1) When DBP was< 95 mmHg with two antihypertensives, the response rate was 1/6 vs. 24/29 for more severe hypertension (P = 0.004). (2) Elderly patients had a response rate of 2/5 vs. 22/24 in younger patients (P = 0.024). (3) Response rates in bilateral and unilateral disease were not different, nor did the function of the affected kidney impact the DBP response. However, three of the four responders with </=10% relative clearance had an occluded renal artery and underwent nephrectomy. CONCLUSIONS: Middle-aged patients with easily controlled hypertension and elderly hypertensives do not usually have a blood pressure response to the performed or attempted invasive treatment of RAD. Therefore, it seems recommendable not to screen such patients for RAD, unless their renal function is deteriorated. If the affected kidney functions poorly on captopril renography, angioplasty is usually not applicable and seldom leads to a blood pressure response.

Adult↗
PubMed2000

Surface UV retrieval from satellite data.

Irradiance of biologically effective ultraviolet radiation on the Earth's surface is retrieved from satellite measurements using radiative transfer models. Retrieval methods are reviewed with a special emphasis on questions pertinent to the Arctic environment. In general, the main problem is the high variability of cloudiness. The most prominent features of high latitudes are the low Sun and the high UV reflectivity of snow-covered terrain. Being white like clouds, snow is a challenge for satellite imagery. The dependence of UV albedo on the properties of snow and ambient conditions is discussed. The use of auxiliary snow cover data from a meteorological model is planned.

Arctic Regions↗
PubMed1999

Renoprotective effects of captopril in hypertension induced by nitric oxide synthase inhibition in experimental nephritis.

OBJECTIVE: To investigate effects of angiotensin I converting enzyme (ACE) inhibition in experimental nephritis during chronic inhibition of nitric oxide (NO) synthase. METHODS: Rats with and without autoimmune Heymann nephritis were treated with a NO synthase inhibitor L-NAME (50 mg/100 ml) and/or an ACE inhibitor captopril (20 mg/100 ml) in drinking water for 12 weeks. Urinary cGMP excretion was used as an indirect measure of NO activity. Blood pressure, urinary albumin, nitrite and nitrate levels, plasma ANP, and plasma renin activity were measured. Kidneys were examined with light microscopy and immunohistochemical methods. RESULTS: Captopril treatment protected rats receiving L-NAME and none of the captopril-treated rats died. Mortality was greatest in the nephritis-L-NAME (57%) and L-NAME (43%) groups. Captopril normalized cGMP excretion, blood pressure, and prevented partly the appearance of albuminuria. Peritubular infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME group (found in 80% of the rats) as compared with the nephritis (20%), L-NAME (40%), and control (0%) groups. The peritubular cell infiltration caused by L-NAME was prevented by captopril treatment. L-NAME-induced hypertension was associated with cardiac hypertrophy and this was prevented by captopril. CONCLUSIONS: NO may play an important renoprotective role in disease progression of chronic membranous glomerulonephritis. Captopril prevents L-NAME-induced hypertension, improves survival, and ameliorates renal damage in this type of nephritis. Dysfunction of renal NO pathways may be an important factor causing progressive renal damage in chronic nephritis. Our results suggest that the dysfunctional renal NO system may be beneficially activated by ACE inhibitors.

Albuminuria↗
PubMed1998

Screening for renovascular hypertension in a population with relatively low prevalence.

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.

Adolescent↗
PubMed1998

Dual inhibition of neutral endopeptidase and angiotensin-converting enzyme in rats with hypertension and diabetes mellitus.

It has been suggested that combined inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may lower blood pressure more effectively than either treatment alone, independent of the degree of salt and volume status or the activity of the renin-angiotensin system. The effects of NEP inhibition in hypertension associated with diabetes mellitus are largely unknown. We therefore compared ACE inhibition, NEP inhibition, and dual NEP/ACE inhibition in diabetic hypertensive rats. Spontaneously hypertensive rats (SHR) aged 9 to 10 weeks were injected with either streptozotocin (45 mg/kg) or citrate buffer and randomized to receive either the ACE inhibitor captopril (25 mg/kg BID), the NEP inhibitor SCH 42495 (30 mg/kg BID), the dual NEP/ACE inhibitor S 21402 (25 or 50 mg/kg BID), or vehicle by gavage for 4 weeks. A group of diabetic SHR was also allocated to receive the combination of SCH 42495 (30 mg/kg BID) and captopril (25 mg/kg BID). The degree of renal NEP inhibition was determined by autoradiography, and plasma renin activity (PRA) was determined by radioimmunoassay. In diabetic SHR, the dual NEP/ACE inhibitor (50 mg/kg BID), as well as the combination of the NEP inhibitor and the ACE inhibitor, reduced systolic blood pressure more effectively than the ACE inhibitor (P<0.001) or the NEP inhibitor (P<0.001) alone. In nondiabetic SHR, the dual NEP/ACE inhibitor and the ACE inhibitor were equally effective, while the NEP inhibitor had only slight blood pressure lowering effects. Relative heart weight decreased in parallel to the changes in blood pressure. Renal NEP was clearly inhibited (70% to 92%; P<0.001) by both the NEP inhibitor and the dual NEP/ACE inhibitor. Both the ACE inhibitor and the dual NEP/ACE inhibitor increased PRA, but the stimulating effect of dual NEP/ACE inhibition on PRA was less than that observed with ACE inhibition alone (P<0.05). Albuminuria in diabetic SHR was lower during treatment with both the dual NEP/ACE inhibitor (50 mg/kg BID) and the combination of NEP inhibition and ACE inhibition compared with vehicle treatment (P<0.05). In conclusion, the present study shows that hypertension in SHR with streptozotocin-induced diabetes is modulated by natriuretic peptides and thus is sensitive to NEP inhibition. The increased efficacy of dual NEP/ACE inhibition on blood pressure in diabetic SHR, compared with ACE or NEP inhibition alone, suggests that this therapeutic approach may prove beneficial in the treatment of hypertension associated with diabetes mellitus and other forms of volume-dependent hypertension.

Analysis of Variance↗
PubMed1996

Chronic inhibition of nitric oxide synthase in Heymann nephritis.

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.

Albuminuria↗
PubMed1996

Polymorphism of the glycogen synthase gene in hypertensive and normotensive subjects.

Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are characterized by a strong genetic component and impaired ability to store glucose as glycogen in skeletal muscle. Impaired insulin activation and altered genetic control of muscle glycogen synthase, the rate-limiting enzyme for glucose storage in skeletal muscle, could provide an explanation for this insulin resistance. We examined whether there is an association between the glycogen synthase gene (Xba I polymorphism) and hypertension in 304 nondiabetic subjects. We examined glucose tolerance with an oral glucose tolerance test and glucose storage in skeletal muscle with the euglycemic insulin clamp technique in combination with indirect calorimetry. The Xba I A2 allele of the glycogen synthase gene was enriched in subjects with hypertension and a family history of NIDDM (48%) compared with normotensive subjects without a family history of NIDDM (6%, P < .0001). The presence of the A2 versus the A1 allele was associated with decreased rates of insulin-stimulated glucose storage in hypertensive subjects (11.2 +/- 2.3 versus 16.9 +/- 2.6 mumol/kg lean body mass per minute, P = .029) but not in normotensive subjects (28.0 +/- 4.6 versus 29.6 +/- 3.7 mumol/kg lean body mass per minute). In conclusion, Xba I polymorphism of the glycogen synthase gene identifies a subgroup of hypertensive subjects with a family history of NIDDM. The data suggest that a locus in the glycogen synthase gene region on chromosome 19 may serve as a "thrifty gene," increasing susceptibility for insulin resistance when exposed to other environmental or genetic factors.

Adult↗
PubMed1995

Increased renal expression of cytokines and growth factors induced by DOCA-NaCl treatment in Heymann nephritis.

DOCA-NaCl treatment causes hypertension, accelerates development of proteinuria, and leads to glomerulosclerosis in rats with autoimmune Heymann nephritis. To study the mechanisms of kidney injury induced by renal haemodynamic load in chronic nephritis, we studied by immunohistochemistry the local expression of various cytokines, growth factors and adhesion molecules in the kidneys of Heymann nephritic rats with or without DOCA-NaCl-induced hypertension. The DOCA-NaCl-nephritis group developed hypertension and marked renal enlargement as compared with the nephritis group, the DOCA-NaCl group, and the controls. Albuminuria appeared earlier and was heavier in the DOCA-NaCl-nephritis group compared with the nephritic rats without DOCA-NaCl. Expression of IL-6, TNF-alpha, GM-CSF, b-FGF, NGF, TGF-beta, and ICAM-1 was enhanced in the kidneys of the DOCA-NaCl-nephritis group as compared with other groups, localized mainly in the glomerular mesangium (IL-6, GM-CSF, TGF-beta), glomerular and peritubular endothelium (ICAM-1), and collecting ducts (TNF-alpha, b-FGF, NGF, TGF-beta), possibly associated with the observed tubulointerstitial mononuclear cellular infiltration. Thus in autoimmune Heymann nephritis, DOCA-NaCl treatment causes hypertension and increased renal mass together with upregulation of local cytokine and growth factor production, which may further aggravate hypertension and accelerate progression of renal damage.

Animals↗
PubMed1992

A study of the effects of lisinopril when used in addition to atenolol.

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.

Adolescent↗
PubMed1991

Prolonged neutral endopeptidase inhibition in heart failure.

We studied the hormonal, renal and hemodynamic effects of prolonged treatment with SCH 39370, a new neutral endopeptidase (NEP) inhibitor, in experimental congestive heart failure (CHF). Coronary-ligated CHF rats and sham-operated controls received vehicle or SCH 39370 30 mg/kg s.c. twice daily for six days. In rats with heart failure, SCH 39370 elevated the high plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) levels 2-fold both initially and at the end of the experiment. Initially, water balance was more negative in SCH 39370-treated CHF rats than in those treated with vehicle. In all SCH 39370-treated rats, ANP, cGMP and electrolyte excretion and diuresis were pronounced for 6 h after injection but attenuated thereafter. Blood pressure and pulse remained unchanged. On reverse phase high performance liquid chromatography (HPLC), ANP-(99-126) appeared to be the only circulating form of ANP in rats with heart failure. Three forms have been discovered in patients with heart failure. HPLC revealed only intact ANP in plasma of rats with heart failure during SCH 39370 treatment. NEP inhibitors may provide a new tool for treating chronic heart failure.

Animals↗
PubMed1990

Raised plasma endothelin-I concentration following cold pressor test.

Plasma concentration of immunoreactive endothelin-1 was measured by radioimmunoassay in 6 healthy subjects before and following cold pressor test by immersion of one fore-arm into ice-water. Mean (SEM) plasma endothelin-1 concentration rose from 1.2 (0.7) to peak value 8.4 (2.3) pg/ml in venous plasma from the immersed hand, and, reaching peak 2 minutes later, from 1.4 (0.5) to 4.6 (2.3) pg/ml in venous plasma from the contralateral hand. In 66 healthy control subjects, venous plasma concentration of endothelin-1 was 2.9 +/- 1.2 pg/ml (mean +/- SD). Exposure to cold is associated with raised blood levels of endothelin-1, which points to a relation between endothelin-1 and vasoconstriction associated with low temperature.

Cold Temperature↗
PubMed1990

Calcium-dependent histidine and histamine release from superfused synaptosomes.

The release of radioactive histidine and histamine was studied in a superfusion system by using guinea pig synaptosomes which were preloaded with 3H-histidine. Depolarization by 50 mM K+ induced a simultaneous release of histidine and histamine. The stimulated release of both of these substances was diminished when calcium was removed. The calcium-dependency of histamine release, previously demonstrated in brain slices, was confirmed using synaptosomes. It was also demonstrated that potassium-induced histidine release from guinea pig synaptosomes under superfusion conditions is at least partially calcium-dependent.

Animals↗
PubMed1990

The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann's nephritis.

Heymann's nephritis was induced with brush-border (BB) antigen. Interstitial mononuclear cell infiltration was studied with cytological examinations of fine-needle aspiration biopsies (FNAB), and with immunoperoxidase stains of frozen sections with monoclonal antisera. The effect of cyclosporin A (CyA), 20 mg/kg when administered intraperitoneally for 8 days in association with both initial immunization, and with the booster 4 weeks later, on the interstitial leukocyte infiltration and on the development of membranous glomerulonephritis (MGN) and proteinuria were investigated. Another group of rats was immunized, but not given CyA. Experimental animals were killed in groups 3, 6 and 20 weeks after initial immunization. CyA inhibited significantly the initial interstitial lymphocyte and blast cell response at 3 weeks (FNAB), but did not inhibit the secondary response after the booster. The anti-BB titre reacted in a similar fashion. Immunoperoxidase stains indicated a clearly suppressed T suppressor/cytolytic (T s/c) cell response. Glomerular basement membrane (GBM) deposits of IgG developed more slowly and were more scarce in the CyA-treated rats, when compared with the untreated group. Only one out of 15 CyA treated rats developed C3 deposits in the GBM during the course of the study, and none developed proteinuria, when most untreated rats (10/17) had C3 deposits and were nephrotic at 20 weeks. Thus, CyA depressed the initial interstitial cellular response after immunization with BB antigen, and also inhibited the development of antibody response, C3 deposits and proteinuria of Heymann nephritis. These effects of CyA may be contributed to an inhibited amplification of the autoimmune response associated with interstitial damage and continuous release of autoantigen.

Animals↗