PubMed Health⌕ Search

Biomedical subjects

I Dotan

Publications and source records attributed to I Dotan.

At least 19 recordsLinked to original sources
PubMed2001

Functional conservation between the human, nematode, and yeast CK2 cell cycle genes.

Protein kinase CK2 (formerly casein kinase II) is a highly conserved serine/threonine protein kinase ubiquitous in eukaryotic organisms. Previously, we have shown that CK2 is required for cell cycle progression and essential for the viability of the yeast Saccharomyces cerevisiae. We now report that either the human or the nematode Caenorhabditis elegans CK2alpha catalytic subunit can substitute for the yeast catalytic subunits. Additionally, expression of the human CK2 regulatory subunit (CK2beta) can suppress the temperature sensitivity of either of the two yeast CK2 mutant catalytic subunits. Taken together, these observations reinforce the view that the CK2 cell cycle progression genes have been highly conserved during evolution from yeast to humans, not only in structure but also in function.

Animals↗
PubMed2001

Genetic synthetic lethality screen at the single gene level in cultured human cells.

Recently, we demonstrated the feasibility of a chemical synthetic lethality screen in cultured human cells. We now demonstrate the principles for a genetic synthetic lethality screen. The technology employs both an immortalized human cell line deficient in the gene of interest, which is complemented by an episomal survival plasmid expressing the wild-type cDNA for the gene of interest, and the use of a novel GFP-based double-label fluorescence system. Dominant negative genetic suppressor elements (GSEs) are selected from an episomal library expressing short truncated sense and antisense cDNAs for a gene likely to be synthetic lethal with the gene of interest. Expression of these GSEs prevents spontaneous loss of the GFP-marked episomal survival plasmid, thus allowing FACS enrichment for cells retaining the survival plasmid (and the GSEs). The dominant negative nature of the GSEs was validated by the decreased resident enzymatic activity present in cells harboring the GSEs. Also, cells mutated in the gene of interest exhibit reduced survival upon GSE expression. The identification of synthetic lethal genes described here can shed light on functional genetic interactions between genes involved in normal cell metabolism and in disease.

Flow Cytometry↗
PubMed2001

Low-dose low-molecular weight heparin (enoxaparin) is effective as adjuvant treatment in active ulcerative colitis: an open trial.

Ulcerative colitis is a chronic inflammatory bowel disorder of unknown etiology. Treatment of flare-ups is based on mesalamine and steroids. Treatment of moderate to severe ulcerative colitis with high-dose heparin and low-molecular-weight heparin was reported. The mechanism was assumed to be a combination of anti-coagulant and anti-inflammatory effects. Low-molecular-weight heparin is better and safer than unfractionated heparin. Studies of low-dose low-molecular-weight heparin in experimental models of inflammation and in inflammatory diseases demonstrated a beneficial effect. Our aim in this study was to evaluate the effect of low-dose, low-molecular-weight heparin in active ulcerative colitis. Twelve patients with flare-ups of colitis were prospectively enrolled. Subcutaneous injections of 5-mg enoxaparin were administered at weekly intervals for 12 weeks. Mesalamine doses remained unchanged. Clinical, laboratory, endoscopic, histologic, and quality-of-life scores were evaluated at the beginning and end of the study. Ten patients completed the study. Mean age was 40.1; the female-male ratio was 7:3. Mean Mayo scores were 9.0 +/- 0.94 at baseline and 3.4 +/- 2.0 at the end of the study (P = 0.0001). Endoscopic scores decreased from 2.2 +/- 0.4 to 1.2 +/- 1.0 (P = 0.049) and in 7 of 10 patients extent of disease shortened. A significant increase in IBDQL scores from 135.7 +/- 37.17 to 179.6 +/- 45.15 points was demonstrated (P = 0.0117). Adverse events were one hospitalization due to abdominal pain, arthralgia (1), transient peripheral edema (1), and elevation of alkaline phosphatase (1). During follow-up, one patient required colectomy and another experienced an exacerbation. In conclusion, low-dose low-molecular-weight heparin once a week, combined with mesalamine, may be an effective therapy for active ulcerative colitis. It may delay or preclude the need for steroid treatment. Controlled studies to evaluate efficacy are needed.

Adult↗
PubMed2001

Heparin and low-molecular-weight heparin (enoxaparin) significantly ameliorate experimental colitis in rats.

BACKGROUND AND AIMS: The anticoagulants, unfractionated heparin and low-molecular-weight heparin, demonstrated anti-inflammatory effects in animal models and in humans. Because of its dual effects, high-dose heparin was proposed as a therapeutic modality for ulcerative colitis. We investigated whether a low dose of low-molecular-weight heparin-enoxaparin (Clexane, Rhône-Poulenc Rorer, France)-ameliorates the inflammatory response in two models of experimental colitis. METHODS: Colitis was induced in rats by intrarectal administration of dinitrobenzene sulphonic acid. Enoxaparin (40, 80 and 200 microg/kg) or unfractionated heparin (100, 200 and 400 U/kg) were administered subcutaneously immediately after the induction of damage. Enoxaparin, 80 microg/kg, was also administered after induction of colitis by intrarectal administration of iodoacetamide. Rats were sacrificed 1, 3 or 7 days after induction of injury. Colonic damage was assessed macroscopically and histologically. Mucosal prostaglandin E2 generation, myeloperoxidase and nitric oxide synthase activities and tumour necrosis factor-alpha levels in blood were determined. RESULTS: Enoxaparin and heparin significantly ameliorated the severity of dinitrobenzene sulphonic acid- and iodoacetamide-induced colitis as demonstrated by a decrease in mucosal lesion area, colonic weight and mucosal myeloperoxidase and nitric oxide synthase activities. The dose-response curve had a bell-shaped configuration: enoxaparin, 80 microg/kg, and unfractionated heparin, 200 U/kg, were the optimal doses. CONCLUSIONS: Low-dose enoxaparin and unfractionated heparin ameliorate the severity of experimental colitis. This effect is related to their anti-inflammatory rather than anticoagulant properties.

Animals↗
PubMed2001

Establishment of a chemical synthetic lethality screen in cultured human cells.

The synthetic lethality screen is a powerful genetic method for unraveling functional interactions between proteins in yeast. Here we demonstrate the feasibility of a chemical synthetic lethality screen in cultured human cells, based in part on the concept of the yeast method. The technology employs both an immortalized human cell line, deficient in a gene of interest, which is complemented by an episomal survival plasmid expressing the gene of interest, and the use of a novel double-label fluorescence system. Selective pressure imposed by any one of several synthetic lethal metabolic inhibitors prevented the spontaneous loss of the episomal survival plasmid. Retention or loss over time of this plasmid could be sensitively detected in a blind test, while cells were grown in microtiter plates. Application of this method should thus permit high throughput screening of drugs, which are synthetically lethal with any mutant human gene of interest, whose normal counterpart can be expressed. This usage is particularly attractive for the search of drugs, which kill malignant cells in a gene-specific manner, based on their predetermined cellular genotype. Moreover, by replacing the chemicals used in this example with a library of either DNA oligonucleotides or expressible dominant negative genetic elements, one should be able to identify synthetic lethal human genes.

Cell Line, Transformed↗
PubMed2001

[Treatment of Crohn's disease with anti TNF alpha antibodies--the experience in the Tel Aviv Medical Center].

TNF alpha is a pro-inflammatory cytokine in Crohn's disease and it's neutralization is beneficial in patients with active disease. Remicade is a chimeric monoclonal anti-TNF antibody. Remicade is used in our center since December 1998 in 13 patients who were treated for active disease or fistula. We followed the patients and treatment results in order to estimate the efficacy and safety of this preparation. Response to treatment was measured by the Crohn's Disease Activity Index (CDAI) in patients treated due to active disease, or by the presence of discharge from external fistulae. Five out of seven patients with fistulae had less or no discharge after completing a course of 3 infusions. Four out of 6 patients treated due to active disease improved significantly after a single infusion. Five out of the six needed additional injections due to symptom recurrence. Intervals between infusions were 2 weeks--for fistulae patients to 32 weeks for patients with active disease. Adverse events for the 13 patients were usually mild except for 4 patients that suffered from anaphylactic shock, disseminated eruption (2) and eosinophilic pneumonitis. In summary, treatment of patients with active Crohn's disease or fistulae with monoclonal anti-TNF antibodies is an effective and relatively safe option after established treatment has failed. Analyzing the results of on going clinical trials and of the patients treated off-protocol will enable to establish new treatment strategies for patients with active Crohn's disease and fistulae.

Adolescent↗
PubMed2000

[Systemic mastocytosis].

Mastocytosis has a highly variable clinical expression, and systemic mastocytosis is occasionally associated with a myeloproliferative or a myelodysplastic disorder. These patients often present without skin involvement and have a very poor prognosis. We report a 72-year-old man with this condition who had spells of flushing and dyspnea, myelofibrosis, and high serum and urine histamine levels.

Aged↗
PubMed1999

The effect of various hormonal preparations and calcium supplementation on bone mass in early menopause. Is there a predictive value for the initial bone density and body weight?

OBJECTIVES: To compare the effect of various oestrogen and oestrogen/progestin preparations on bone density over a 2-year follow-up period in early postmenopausal women. SETTING: A retrospective study on 315 women followed in a menopause clinic. DESIGN: Antero-posterior lumbar spine bone densitometry was performed at baseline and between 18 and 24 months (mean 22 months) after initiation of hormone therapy. Participants were divided into six groups: women taking conjugated equine oestrogen (CEE) (n = 30); CEE plus sequential monthly medroxyprogesterone acetate (MPA) (n = 52); CEE plus sequential bimonthly MPA (n = 51); oral estradiol plus sequential monthly norethisterone acetate (n = 52); transdermal estradiol plus sequential monthly MPA (n = 30). A control group (n = 100) was composed of nonusers of hormones. RESULTS: Hormone users, as a whole (n = 215), increased their bone mineral density (BMD) by 2.9% (4.8) as compared to the controls who lost 3.5% (3.4; P < 0. 001). There were similar gains in BMD amongst the five study groups. Calcium supplementation was associated with better results in all women: users of hormones and calcium had a gain in BMD of 4.5% (4.8) compared to only 1.5% (4.5) in those on hormones but without calcium (P < 0.001); amongst the controls, women using calcium lost 1.4% (2. 4), whilst nonusers of calcium lost 3.7% (2.4; P < 0.001). A dose-response curve was found between basal BMD and the effect of hormone therapy: women with osteoporosis (T-score <75%) demonstrated the largest increase in BMD - 6.3% (4.6), osteopenia (T-score 75-85%) was associated with a gain of 3.2% (5.6), low-borderline values (T-score 86-100%) gave a modest increase of 1.3% (4.3), and those with more than average BMD values (T-score >100%) actually lost bone despite hormone treatment [-2.1% (4.1)]. CONCLUSIONS: All hormone regimens had a similar bone conserving effect. Basal BMD value may serve as a predictor for the success of treatment. Calcium supplementation should be recommended in all postmenopausal women.

Body Weight↗
PubMed1999

Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism.

AIMS/BACKGROUND: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. METHODS: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). RESULTS: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-alpha and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean+/-SE AST: 1499+/-18 vs 78+/-10 IU/l, p<0.001; TNF: 2500+/-250 vs 135+/-15 pg/ml, p<0.001, IL-6: 12,200+/-300 vs 1260+/-140 pg/ml, p<0.001, respectively). CONCLUSIONS: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases.

Alanine Transaminase↗
PubMed1999

Altered thyroid status modulates portal pressure in normal rats.

BACKGROUND & AIMS: Disturbances in thyroid function in humans and experimental animal models have been associated with alterations in liver function and portal circulation. We have previously shown that hypothyroidism can significantly reduce portal pressure in portal vein ligated rats as well as inhibit the development of cirrhosis and fulminant hepatic failure following toxic liver injury. The aim of this study was to determine the effects of increased and decreased thyroid function on portal pressure in rats with normal liver histology and portal circulation. METHODS: Three groups of 12 Wistar rats each were studied over a 30 day period: euthyroid (Group 1), hyperthyroid (Group 2) and hypothyroid (Group 3). Hyperthyroidism was induced by subcutaneous injection of triiodothyronine (400 microg/100g body weight) every ten days during the study period. Hypothyroidism was induced by methimazole (0.04% in drinking water) from 2 weeks prior to and throughout the 30 day study. Serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were determined to confirm the induction of hyper- and hypothyroidism. Portal pressure was assessed by direct catheterization of the portal vein prior to sacrifice. Indirect confirmation of changes in portal circulation was obtained by determining splenic weight at the time of sacrificing the animals. Animals were sacrificed at 10 day intervals throughout the 30 day study. RESULTS: Triiodothyronine treated rats were hyperthyroid compared to controls, with an elevation in serum T3 levels (3.8+/-0.9 mmol/L vs 1.3+/-0.4 mmol/L, p<0.05). In rats treated with methimazole, hypothyroidism was confirmed by a 7-fold increase in serum TSH compared to controls (1.8+/-0.4 vs 0.24+/-0.04 mmol/L, p<0.01). Portal pressure was significantly higher in the triiodothyronine treated rats compared to controls (12.8+/-1.7 and 9.6+/-0.75 cm H2O, p<0.001). Splenic weights in hyperthyroid rats were significantly higher than in controls (579+/-44 vs 478+/-46 mg, p<0.01). Portal pressure was significantly lower in the methimazole treated group compared to the control group (8.13+/-0.68 vs 9.6+/-0.75 cm H2O, p<0.01) as were splenic weights (400+/-33 vs 478+/-46 mg, p<0.01). CONCLUSION: These studies demonstrate that disturbed thyroid function exerts significant hemodynamic effects on the portal circulation in normal rats and complements results from previous similar studies in cirrhotic animals.

Administration, Oral↗
PubMed1999

L-thyroxine prevents the bone-conserving effect of HRT in postmenopausal women with subclinical hypothyroidism.

Hypothyroidism, which is a common disorder among postmenopausal women, may be associated with higher than average bone mineral content. Contrarily, treatment with L-thyroxine may cause a significant bone loss. The aim of our study was to evaluate the effects of hormone-replacement therapy (HRT) on bone density in women with subclinical hypothyroidism treated with L-thyroxine. A total of 73 postmenopausal women with thyroid-stimulating hormone (TSH) levels > 5 mU/l and normal free thyroxine values, who never used HRT or L-thyroxine, were divided into three groups according to the treatment given during a 3-year follow-up period: 34 women received only HRT; 20 women received HRT and L-thyroxine, and the remaining 19 women received neither medications. A euthyroid control group included 41 postmenopausal women with TSH levels between 0.5 and 1.5 mU/l, who were using HRT since the initial visit. Lumbar spine bone density measurements were performed at baseline and study termination. Taken as a whole, the hypothyroid women had a non-significant higher baseline bone mineral density (BMD) as compared to the euthyroid controls (1.068 +/- 0.19 g/cm2 vs. 1.024 +/- 0.15). After 3 years, both the euthyroid and hypothyroid women on HRT only had an increase in BMD (0.032 +/- 0.04 g/cm2 and 0.028 +/- 0.05 g/cm2, respectively; p < 0.001 for both, compared to baseline). Hypothyroid women using no medication had a decrease of 0.034 +/- 0.07 g/cm2 in BMD, and those receiving both HRT and L-thyroxine lost the most: 0.04 +/- 0.08 g/cm2 (p < 0.05 for both, compared to baseline). The addition of L-thyroxine thus prevented the beneficial effect of HRT on BMD. Thyroid hormone replacement is recommended only when overt symptoms of hormone deficiency occur. In such cases, a single bone-conserving treatment with HRT may not suffice.

Adult↗
PubMed1998

Thyroxine accelerates proliferation of injured liver cells.

BACKGROUND/AIMS: Long-term gene transfer into hepatocytes requires DNA synthesis. Although this can be achieved in vitro, using various hepatic mitogens, marked proliferative response is not seen in vivo in the quiescent liver. We have speculated that controlled reversible liver damage might change the steady state of the liver, and thus render it susceptible to manipulations by growth factors and cytokines. Therefore, the influence of thyroxine on proliferation of hepatocytes and of bile duct epithelial cells was investigated, using an in vivo model of thioacetamide-induced liver insult. METHODS: Five groups of ten rats each were studied: normal rats, thioacetamide-treated, thyroxine-treated, both thioacetamide and thyroxine-treated, and a 70% partial hepatectomy group. DNA synthesis was looked at by PCNA labeling. RESULTS: The PCNA labeling indexes of hepatocytes and of bile duct epithelial cells in rats treated with both thioacetamide and thyroxine (9.5+/-1.2 and 33.8+/-5.7% respectively) were significantly (p<0.0002) higher than those of the normal (0.84+/-0.2 and 4.4+/-0.50%), thioacetamide-treated (2.1+/-0.3 and 7.1+/-2.3%) and thyroxine-treated animals (0.6+/-0.3 and 11+/-5.6%). The labeling index in the hepatectomized animals was significantly higher for hepatocytes (18.3+/-1.2%, p<0.003), but lower for biliary cells (15+/-2.6, p<0.05) than that observed in thioacetamide and thyroxine-treated rats. Hypothyroid rats had significantly lower PCNA labeling index, as compared to the thioacetamide-thyroxine-treated group or the partial hepatectomy group. CONCLUSIONS: Following controlled liver damage, thyroxine is a potent mitogen for both hepatocytes and bile duct epithelial cells.

Animals↗
PubMed1998

Effect of estradiol on rat ileum.

1. Sex hormones may influence gastrointestinal motility and thus may be responsible for symptoms that are common during pregnancy or hormone replacement therapy. The purpose of this study was to evaluate the effect of estradiol on the gut. 2. Segments of rat ileum (n=9) were suspended in an organ bath and exposed to increasing concentrations of carbachol, in the presence or absence of 17beta-estradiol. 17beta-estradiol markedly reduced the force developed by the ileum in response to carbachol. 3. These results suggest that estradiol reduces gastrointestinal motility.

Animals↗
PubMed1998

Liver function in cirrhotic patients in the euthyroid versus the hypothyroid state.

We recently showed that some decrease in thyroid hormone blood levels can effectively and significantly prevent the development of cirrhosis and fulminant hepatic failure and decrease portal pressure in three different rat models. This study was conducted to determine whether hypothyroidism has a beneficial effect over euthyroidism on patients with active liver cirrhosis of different etiologies. The medical files of hypothyroid patients with cirrhosis who were referred to the Tel-Aviv Medical Center between the years 1980 and 1995 were retrospectively evaluated. Of 3,528 patients with biopsy-proven cirrhosis and 4,738 hypothyroid patients who were identified, only 46 (25 female, 54%; mean age, 52.3 +/- 9.1) met the eligibility criteria. The patients suffered from cirrhosis (mean, 9.5 +/- 4.3 years; range, 4-23) and had hypothyroidism (mean, 12 +/- 6 years; range, 4-31). Most patients suffered from hypothyroidism of unknown etiology (85%), whereas the rest had hypothyroidism after surgical/iodine ablation of the gland. In the hypothyroid versus the euthyroid state, a significant negative correlation was found between thyroid-stimulating hormone blood levels and both functional and synthetic liver function tests (p < 0.001). A significant negative correlation was also found between thyroid-stimulating hormone blood levels and clinical deterioration manifested as bleeding varices, the development of ascites, and episodes of encephalopathy. We conclude that in patients with liver cirrhosis, the liver function in the hypothyroid state tend to be better than in the euthyroid state. A mild controlled decreased thyroid function may be beneficial for euthyroid cirrhotic patients.

Acute Disease↗
PubMed1998

Hormone replacement and simvastatin in the therapy of hypercholesterolemic postmenopausal women.

OBJECTIVES: To prospectively investigate the effect of cholesterol lowering diet, hormone replacement therapy and simvastatin on plasma lipid levels using a 3-month stepwise protocol. METHODS: Participants were postmenopausal women under the age of 60 with hypercholesterolemia (plasma total cholesterol > 240 mg/dl). The study started with 3 months of Step-One diet (phase I) followed by 3 months of diet and hormone replacement therapy (0.625 mg conjugated estrogens daily combined with 5 mg medroxyprogesterone acetate at days 13-25 of each cycle) (phase II). In women whose total cholesterol remained above 240 mg/dl or LDL-cholesterol above 160 mg/dl by the end of phase II, simvastatin at 10 mg daily was added (phase III). Plasma cholesterol levels as well as safety measurements were closely monitored. RESULTS: Sixteen (21%) of 75 patients who entered the study had satisfactory cholesterol levels by the end of 6 months. Another 25 patients (33%) dropped out of the study for various reasons by that time. In the 34 patients who started simvastatin, plasma total cholesterol levels did not significantly change during phase I and II, however, LDL-cholesterol significantly decreased (204 +/- 31 to 187 +/- 26 mg/dl, p = 0.04) and HDL increased (53 +/- 12 to 62 +/- 16 mg/dl, p = 0.04). A dramatic decrease occurred in both total and LDL-cholesterol levels after one month of phase III (281 +/- 26 to 213 +/- 30 mg/dl 187 +/- 26 to 122 +/- 30 mg/dl respectively, p < 0.0001), with no further changes during the rest of the study period. No significant changes occurred in HDL-cholesterol and triglyceride plasma levels at this phase. Adverse effects were few and minor throughout the study. CONCLUSIONS: Some of the hypercholesterolemic postmenopausal women will benefit from hormone replacement therapy as a single cholesterol lowering treatment in addition to diet (21% in our series). Nevertheless, combination therapy of estrogens and low dose simvastatin proved to be extremely effective in lowering cholesterol levels with no significant side effects. Such therapeutic regimen may also have a synergistic anti-atherogenic effect.

Anticholesteremic Agents↗
PubMed1997

Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus.

A human cDNA previously isolated by virtue of its ability to complement partially the ultraviolet sensitivity of a xeroderma pigmentosum cell line was further characterized. The transcription unit is expressed as a single 4.0-kb mRNA that encodes a novel 63-kDa cytoplasmic protein, possibly initiating from an internal AUG codon. The gene encoding this protein, named UVRAG, has been extremely well conserved during evolution, implying an important role for this gene product in cell metabolism. The transcribed mRNA is constitutively expressed in a wide variety of human tissues. The protein encoded by this gene is predicted to contain a coiled-coil structure and is likely to be metabolically unstable based on the occurrence of a strong PEST domain. UVRAG was assigned to human chromosome 11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ hybridization coupled with PCR analysis of human/rodent somatic cell hybrids containing segments of human chromosome 11 has localized this gene to a subregion of 11q13 in between the D11S916 and the D11S906 loci. Importantly, this region has been shown to be amplified in a variety of human malignancies, including breast cancer.

Amino Acid Sequence↗
PubMed1996

Prediction of renal impairment in elderly patients with congestive heart failure treated with captopril.

This study assessed the usefulness of the oral captopril test in the prediction of renal impairment among elderly patients with congestive heart failure (CHF). Forty-seven patients aged > or = 65 years with CHF (EF < 40%) participated in a prospective nonrandomized series. Blood samples for plasma renin activity (PRA) were drawn before and 60 minutes after 50 mg of oral captopril. Twenty-four hours later, captopril was administered (up to 75 mg/day over a 4 day period), and renal laboratory and clinical assessment were performed at baseline and for a 9 day period. In 7 of 47 patients (14.9%), deterioration of renal function was observed. During the captopril test, the PRA increased significantly after 1 hour in almost all patients and the mean blood pressure decreased from 99.2 +/- 14.6 mmHg to 92.2 +/- 13.7 mmHg (p < 0.001). All patients whose baseline PRA level was < 1.9 ng/ml/hr and whose stimulated PRA was < 3.2 ng/ml/hr maintained a stable renal function throughout the study period. Significant statistical correlation (p < 0.05) was found between the initial PRA, the changes in PRA or mean blood pressure during the captopril test, and the change in plasma creatinine and creatinine clearance in the entire group, and was even more evident in a subgroup of patients with an ejection fraction > or = 30%. All these correlations were not statistically significant in the patients with an ejection fraction < 30%. It is thus concluded that measurement of pretreatment PRA levels might be a useful laboratory tool for predicting the renal safety of captopril use in patients with CHF whose EF > or = 30%.

Administration, Oral↗