Steroid-treated Group Research Articles

Differential regulation of oxytocin and vasopressin messenger ribonucleic acid levels by gonadal steroids in postpartum rats

We previously reported that sequential estradiol and progesterone exposure followed by progesterone withdrawal increases oxytocin (OT), but not arginine vasopressin (AVP), messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus (PVN) of the rat. Substitution of testosterone for progesterone and subsequent testosterone withdrawal in the estrogen-primed rat increases PVN AVP mRNA levels. At the end of pregnancy (day 21), rats are exposed to high estrogen and declining progesterone and testosterone concentrations. Coincident with these changes in circulating gonadal steroid hormones are increases in OT and AVP mRNAs. If progesterone levels are sustained at term, OT levels are attenuated and if testosterone is sustained, AVP mRNA levels are attenuated. Immediately postpartum, however, OT and AVP mRNA levels decline compared to term levels. To further determine the role of estrogen in the regulation of OT and AVP mRNAs, we performed two experiments. In the first experiment, we administered estrogen during the peripartum period to determine if estrogen supplementation prevents the relative attenuation of OT and AVP mRNAs that is seen after parturition. Day 18 pregnant rats were given estradiol-filled or empty capsules and sacrificed on day 2 of lactation. By Northern analysis, significant differences in PVN AVP, but not OT, mRNA were found between the estrogen- and sham-treated lactational animals, P < 0.02. In the second experiment, we determined if sustaining estrogen after progesterone is removed in steroid-treated ovariectomized rats is essential for the increase in OT mRNA. Ovariectomized rats were given either empty capsules or sequential estradiol- and progesterone-filled capsules and both were sustained for 12 days. When progesterone-filled capsules were removed, estradiol-filled capsules were either removed or left in place, and the animals were sacrificed 48 h later. PVN OT mRNA was analyzed by Northern blot hybridization. OT mRNA was increased in both of the steroid-treated groups to the same degree, compared to sham-treated animals, P = 0.04. In summary, estrogen supplementation during early lactation prevents the attenuation of PVN AVP, but not OT, mRNA after parturition. In the estrogen-primed ovariectomized rat, it is not necessary to sustain estrogen to see the effects of progesterone withdrawal upon PVN OT mRNA.

Does Steroid Medication Reduce Facial Edema Following Face Lift Surgery? A Prospective, Randomized Study of 30 Consecutive Patients

A prospective, double-blinded study of 30 consecutive face lift patients was conducted to determine if the administration of corticosteroid medication would reduce postoperative facial edema. Half the patients received steroid medications in a random fashion. Three independent plastic surgeons who were blinded to the study rated facial swelling by comparing preoperative and postoperative photographs using a scale of 1 to 4. The data were tabulated and subjected to statistical analysis. There were no significant differences in facial swelling between the steroid-treated group and the untreated patients on any occasion.

Effects of acute steroid administration on ventilatory and peripheral muscles in rats.

Occasional case reports have shown that acute myopathy may occur in patients treated with massive doses of corticosteroids. The mechanism of this myopathy is poorly understood. Therefore, 60 male rats were randomly assigned to receive daily injection of saline (C), methylprednisolone (M), or triamcinolone (T) 80 mg/kg/d for 5 d. Nutritional intake, measured daily in 15 animals, showed a significant reduction of food intake in the steroid-treated groups (-50 and -79% in M and T, respectively). This was associated with a similar loss in body weight. In the 45 remaining animals, diaphragm contractility and histopathologic features of several muscles were studied. Weights of respiratory and peripheral muscles were similarly decreased after steroid treatment. Maximal twitches of the diaphragm were lower in the C group (653 +/- 174 g/cm(2)) than in the M group (837 +/- 171 g/cm(2); p < 0.05) and the T group (765 +/- 145 g/cm(2), NS). Half-relaxation time was prolonged in both steroid groups, and time to peak tension was longer with M, whereas tetanic tensions were similar. Steroid treatment also induced a leftward shift of the force-frequency curve at 25 and 50 Hz when compared with saline treatment (p < 0.05). ATPase staining of the diaphragm, scalenus medius, and gastrocnemius showed type IIb fiber atrophy in the steroid groups and also diaphragmatic type IIa atrophy with T, whereas histologic examinations revealed a normal muscular pattern with absence of necrosis. Finally, a pair-fed (PF) study, performed in 18 rats (C, T, and PF), showed that muscle atrophy was considerably less pronounced in PF animals than in T-treated animals. We conclude that (1) short-term treatment with massive doses of steroids induced severe respiratory and limb muscle wasting; (2) both types of steroids induced predominantly type IIb atrophy, resulting in the expected alterations in diaphragm contractile properties; (3) neither steroid caused muscle necrosis; (4) type IIb atrophy was not caused by acute nutritional deprivation alone.

Early corticosteroid use in acute exacerbations of chronic airflow obstruction

To determine the benefit of early steroid use in acute exacerbations of chronic airflow obstruction in the ED, 113 patients with an average age of 66 years, acute or chronic dyspnea, an FEV 1 of <60% and FEV 1 FVC ratio of <60% were included in a randomized, double-blinded, interventional clinical trial. All patients received the same bronchodilator treatment. At 6 hours the steroid-treated group showed a 21.71 L/min improvement in PEFR ( P < .05) and 0.14 L improvement in FEV 1 ( P < .05), while the nonsteroid group showed insignificant improvements of 5.52 L/min and 0.02 L, respectively. Of those patients receiving steroids, 22 achieved >40% improvements in PEFR by 6 hours and 17 achieved similar results in FEV 1, whereas of those not receiving steroids, 13 and 8, respectively, achieved improvements. Within 24 hours of observation in the ED, 16 patients receiving steroids were discharged and none relapsed within 2 weeks. Of those not receiving steroids, only 10 were discharged and 3 returned with exacerbations. Although early response to steroids in chronic airflow obstruction is variable, the overall medical and cost benefits justify their early use in acute exacerbations.

A new steroid-induced cataract model in the rat: long-term prednisolone applications with a minimum of X-irradiation.

In order to induce experimental steroid cataracts in rat eyes similar morphologically to those seen in human eyes, prednisolone acetate was administered either topically or systemically for 12 months with a low dose of X-irradiation as a cocataractogenic factor. Twenty-seven Brown-Norway rats were randomly divided into a control group (group I) with no steroid administration; an eyedrop group (group II) with a daily 1% prednisolone acetate instillation of a total volume of 1.0 mg/kg in both eyes, and a systemic group (group III) with a daily intramuscular injection of 0.8-1.0 mg/kg prednisolone acetate. The right eyes of animals in each group were X-irradiated with a single dose of 2 Gy. Topical and systemic steroid administrations started 2 weeks after X-irradiation. Anterior segment changes were documented with a slitlamp microscope and an anterior eye segment analysis system once a month. Body weight and blood glucose levels were examined every week and every 2 weeks, respectively. The mortality rates in groups I, II and III were 0, 11 (1/9) and 25% (3/12), respectively. The both lenses in group I showed a gradual increase in light-scattering intensity in the nuclear and supranuclear regions over time. Initial lens changes in both steroid-treated groups were Y-suture dissociation and a slight increase in light-scattering intensity in the posterior supranuclear region 3 months after prednisolone administration. Opacification of the anterior shallow cortex and the posterior subcapsular layer was observed after 10 months. X-irradiated eyes showed more prominent lens opacification as compared with nonirradiated eyes after 10 months in both group II and group III. Either topical or systemic administrations of prednisolone acetate over a long term successfully induced morphological lenticular changes in the rat similar to those found in human steroid-induced cataracts. A low dose of X-irradiation effectively accelerated opacification as a cocataractogenic risk. This new model will allow future investigation of steroid cataracts.

Use of corticosteroids in the prevention of post-ERCP pancreatitis

Background: Pancreatitis frequently complicates diagnostic and therapeutic ERCP. A variety of causes have been implicated. A number of different agents have been used, without success, in an attempt to prevent pancreatitis. Methods: In the current study, 824 patients with a history of iodine sensitivity were given preprocedure corticosteroid therapy (651 oral steroids and 173 intravenous steroids) in an attempt to prevent allergic reactions. These patients were retrospectively studied in an attempt to determine if corticosteroid administration prevents ERCP-related pancreatitis. Two control groups were used for comparison, including 1000 patients during the same study period (Control Group I) and 1954 patients from the Midwest Pancreaticobiliary Group (Control Group II). Results: There was a significant difference in the overall incidence of post-ERCP pancreatitis in the corticosteroid treated group (4.6%) compared with either control group (Control Group I = 7.4% and Control Group II = 9.1%). Of those patients undergoing therapeutic ERCP, results were even more significant in favor of the steroid-treated group (5.2%) compared with Control Group I (9.7%) and Control Group II (11.2%). Conclusions: These results demonstrate that the administration of corticosteroids prior to ERCP results in a decreased incidence of post-ERCP pancreatitis. A prospective, randomized, controlled trial is warranted. (Gastrointest Endosc 1995;42:579-83.)

Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess

The aim of our study was to investigate the effect of hexarelin, a novel GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied seven adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non-endocrine diseases (six females and one male, age range 42-68 years) and one subject (female, age 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and age with the patients and not undergoing any therapy served as controls. All the subjects underwent the following three tests in random order: (1) human GHRH (1-29)NH2 (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min, (2) hexarelin (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min and (3) hexarelin (100 micrograms in 1 ml of saline) plus GHRH (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min. After GHRH alone the patients with glucocorticoid excess showed a blunted GH response as compared with normal subjects (median delta GH: 0.9, range 0-5.6 micrograms/l vs 7:1, range 0.3-14.9 micrograms/l). No significant differences were observed in the steroid-treated group with respect to normal subjects after hexarelin alone (median delta GH: 15.5, range 1.9-45.2 micrograms/l vs 17.9, range 5.5-53.9 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of pregnenolone sulfate and ethylestrenol on retention of a passive avoidance task

Two experiments using male rats evaluated the effects of a range of doses of the neurosteroid, pregnenolone sulfate (PS), or of the synthetic neurosteroid, ethylestrenol (E), on the retention of a passive avoidance task. The steroids either were given immediately after the training trial or 1 h before the first retention test. Retention tests were given both 24 h and 48 h after acquisition. In both experiments, separate groups of animals were trained under low or moderate footshock conditions. At all doses tested both PS and E improved retention under the low footshock conditions. In groups trained with the higher footshock, the steroid-treated groups performed no better than the vehicle controls. Indeed, there were suggestions that some doses impaired retention. These results seem best understood as an induction of bimodality or ‘turbulence’ in behavior as used in Chaos theory rather than a shift in an inverted U-shaped retention function. In the second experiment in which the steroids were given before retention testing, they were generally without effect.

Basophils and eosinophils in allergic rhinitis

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Postpartum corticosteroids: Accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP)

Because most morbidity and mortality associated with atypical preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets is a postpartum phenomenon, we undertook this investigation to evaluate the use of high-dose corticosteroids to minimize maternal morbidity and accelerate postpartum recovery in patients with this form of severe preeclampsia. Into this prospective, randomized study 40 parturients with the syndrome were recruited. The syndrome was defined by a clinical presentation consistent with a diagnosis of severe preeclampsia or eclampsia in addition to laboratory evidence of hemolysis, hepatic dysfunction, and thrombocytopenia. Immediately post partum 20 parturients assigned to the treatment group received four doses of intravenous dexamethasone at 12-hour intervals (10 mg, 10 mg, 5 mg, 5 mg) over 36 hours. Patients assigned to the control group received no corticosteroids. All study subjects were intensively monitored by mean arterial pressure and urinary output every 2 hours, hematocrit and platelet count every 6 hours and lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase every 12 hours for the first 48 hours post partum. The steroid-treated group with the syndrome of hemolysis, elevated liver enzymes, and low platelets had significant changes over time in mean arterial pressure, urinary output, platelet count, lactic dehydrogenase and aspartate aminotransferase versus the control group with the syndrome. Relative to the control group, the mean arterial pressure became significantly decreased at 22 hours in the steroid-treated group (p < 0.03), urinary output increased significantly by 16 hours (p < 0.02), the platelet count increased significantly by 24 hours (p < 0.05), and both lactic dehydrogenase and aspartate aminotransferase decreased significantly by 36 hours (p < 0.04 and p < 0.05, respectively). In association with high-dose corticosteroid administration, parturients with the syndrome of hemolysis, elevated liver enzymes, and low platelets recovered from the disease process more rapidly than did control subjects, as measured by urinary output, mean arterial pressure, platelet count, lactic dehydrogenase, and aspartate aminotransferase. In this disease process, which has significant associated morbidity and mortality, especially in patients with advanced cases, high-dose corticosteroid therapy appears to significantly hasten recovery and lessen the severity of the disease post partum. We postulate that use of this therapeutic approach in properly selected patients could result in lessened overall maternal morbidity and mortality, shorter patient stays in recovery and intensive-care areas, and shorter overall hospitalization with reduced medical care costs.

Corticosteroids Enhance S-Antigen Expression in Nonretinal Ocular Tissues of Rats with Experimental Autoimmune Uveitis

S-antigen (S-Ag), a major protein on the retinal photoreceptor cell, can induce experimental autoimmune uveitis (EAU). We have previously detected S-Ag and its mRNA in irises of chronic uveitis patients receiving long-term steroid therapy. To further investigate the effect of steroid therapy on ocular tissue, we compared levels of S-Ag and its mRNA in EAU rats with and without steroid treatment. EAU was induced in 72 Lewis rats by two footpad injections of S-Ag. The rats were then treated with Depo-Medrol or phosphate-buffered saline by intramuscular injection. Eyes were collected at different time points. S-Ag mRNA was detected in the lens epithelium, trabecular meshwork, iris, and ciliary body of 47.2% of the steroid-treated group vs 22.2% of the controls. S-antigen was also detected in 30.6% of the eyes of the treated group vs 16.7% of the controls. S-Ag and its mRNA was found only in the retina of normal rats. These results support the hypothesis that prolonged corticosteroid therapy in uveitic patients might enhance the expression of S-Ag in nonretinal ocular tissues and might contribute to the ocular side effects of corticosteroid.

Effects of anabolic steroids and endurance exercise on cardiac performance.

This study examined the effects of anabolic steroids and exhaustive endurance exercise, and the combination of both treatments on in vitro cardiac contractile function. Fifty-two male Sprague-Dawley rats were randomly assigned, in groups of 13, to one of the four groups: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid treated (E+S). Nandrolone decanoate was administered to the steroid-treated groups every 7-9 days during the 10 weeks study, while the C and E groups received glycerol injection on these occasions. The exercised rats ran on a treadmill wearing a collar weight (2-3% of body weight) for 50 min, 5 days a week. In vitro ventricular performance was assessed in isolated Langendorff perfused hearts in response to increasing left ventricular balloon volumes. Left ventricular +dP/dt, dP/dt at 60 mmHg developed pressure, tension time index, and Emax (slope of the pressure-volume curves) were significantly (p < 0.05) lowered in the E+S group, as compared to the C, E, or ST group. Meanwhile, the E group exhibited a higher (p < 0.05) left ventricular systolic pressure (LVSP) than the C and E+S groups. No significant differences in dP/dt/P, heart weight (wt), and heart wt to body wt ratio were detected among the four groups. Rats subjected to endurance exercise or anabolic steroid treatment alone exhibited no change in LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver.

The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.

Corticosteroids for the enhancement of fetal lung maturity: impact on the gravida with preeclampsia and the HELLP syndrome.

This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980-1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p < 0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p < 0.008) than in untreated patients.

Corticosteroids for enhanced fetal lung maturation in patients with HELLP syndrome: impact on neonates.

This study was undertaken to determine retrospectively, in women with the HELLP syndrome, the perinatal effects of corticosteroid administration for promotion of fetal lung maturity. Twenty-seven of 427 women with the HELLP syndrome treated between 1980 and 1991 received a full course of steroids prior to preterm delivery. They were compared to 27 control patients with the HELLP syndrome matched for maternal age, severity of disease, gestational age, race, and sex of the fetus. Respiratory distress requiring mechanical ventilation occurred in 13 of 27 neonates who received steroid administration and in 23 of 27 who did not receive steroids (p < 0.001). The average stay in the neonatal intensive care unit was 29.8 +/- 50.6 days for the steroid-treated group and 45.2 +/- 35.3 days for the group without steroid use (p = NS). The incidence of neonatal deaths, intraventricular haemorrhage type III and IV, necrotizing enterocolitis, and retrolental fibroplasia was greater in the control group but the difference was not statistically significant.

Bone mineral density of the hip and of the anteroposterior and lateral dimensions of the spine in men with rheumatoid arthritis. Effects of low-dose corticosteroids.

To assess bone mineral density (BMD) in men with steroid-treated rheumatoid arthritis (RA). Dual-energy x-ray absorptiometry (DXA) was used to measure BMD in 40 men with RA, 20 of whom were receiving low-dose corticosteroids (< or = 10 mg prednisolone daily), and in 20 healthy, age-matched male controls. BMD was significantly reduced at the femoral neck and greater trochanter in both groups of RA patients, and at the spine from the anteroposterior dimension in the steroid-treated group. Low-dose steroid therapy may induce excess axial osteopenia in men with RA.

Effects of oral administration of anti-inflammatory doses of prednisone on thyroid hormone response to thyrotropin-releasing hormone and thyrotropin in clinically normal dogs

SUMMARY Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl). Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean ± SEM, 2.58 ± 0.28 or 3.38 ± 0.58 μg/dl, respectively) vs dogs of the Ctrl group (2.12 ± 0.30 μg/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropinreleasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P&lt; 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT4 concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 ± 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 ± 4.3 ng/dl) and Pred (28.9 ± 3.8 ng/dl) groups after 4 weeks of medication. These data indicate that daily oral administration of such anti-inflammatory dose of prednisone for 1 month reduces baseline serum T3 concentration, does not alter serum T4 concentration, and enhances thyroidal sensitivity to thyrotropin.

Effects of sex steroid implants on reproductive tissues of female garter snakes (Thamnophis sirtalis).

Female Thamnophis sirtalis were administered intraperitoneal implants of either estradiol 17β (E2), testosterone (T), 5α-dihydrotestosterone (DHT), or empty silastic capsules for 3 weeks. Plasma levels of E2 and T, measured by specific radioimmunoassay, were significantly elevated in E2 and T-implanted females when compared to controls. T-implanted females did not have elevated circulating E2 levels, suggesting that E2 in the plasma normally is not derived from peripheral conversion of T to E2. Implantation of DHT did not significantly change circulating levels of E2, T, or DHT. All three sex steroid-treated groups of animals had increased oviductal mass compared to controls, while hepatic mass of only E2-treated animals was significantly greater. None of the steroid treatments influenced ovarian mass. Oviductal epithelial cell height and area were greater in the three steroid-treated groups. Testosterone increased myometrial area while DHT drastically altered oviductal morphology. Hepatic cell area and number increased significantly in E2-treated females. However, a small increase in both hepatic cell area and number was noted in T- and DHT-treated females as well. These results suggest that androgen in both an aromatizable and non-aromatizable form can affect the oviduct of females but that the liver primarily responds to estrogenic steroids. © 1992 Wiley-Liss, Inc.

The Effect of Glucocorticosteroids on Serum, Liver, and Lung Vitamin A and Retinyl Ester Concentrations

Vitamin A and its active metabolites are important factors in promoting normal respiratory epithelial differentiation and growth. Glucocorticoids, often used to treat chronic lung diseases in infancy and childhood, are known to increase serum retinol concentrations. To determine the effects of exogenous steroids on serum retinol and retinol-binding protein concentrations (as well as on liver and lung total vitamin A, retinol, and retinyl ester concentrations), 32 weanling Sprague-Dawley rats were divided into four equal experimental groups. Eight animals were vitamin A sufficient and received 7 days of intraperitoneal dexamethasone at 0.5 mg/kg/day (group SD), 8 were vitamin A sufficient and received placebo (group SP), 8 were made vitamin A deficient and subsequently received dexamethasone (group DD), and 8 were vitamin A deficient and received placebo (group DP). Dexamethasone increased serum retinol concentrations in the SD group (2.27 +/- 0.20 mumol/L) when compared with control (SP, 1.64 +/- 0.46 mumol/L, p less than 0.001) as well as with pretreatment baseline values (1.21 +/- 0.23 mumol/L, p less than 0.001). Lung total vitamin A, retinol, and individual retinyl esters were depleted by 56 +/- 19% in the SD group, whereas liver values were depleted by 36 +/- 23%. In the vitamin A-sufficient groups the relative percentages of four major retinyl esters (palmitate, stearate, oleate, and linoleate) did not change in either tissue after steroid exposure. The vitamin A-deficient groups had no detectable tissue vitamin A, and dexamethasone did not increase serum retinol concentrations in the DD group. Serum retinol-binding protein concentrations were significantly higher in both steroid-treated groups when compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal sclerosing glomerulopathy risk factors of progression and optimal mode of treatment

Focal sclerosing glomerulopathy and especially focal segmental glomerulosclerosis (FSGS) have been recognized as a distinct clinical entity, however, there still exist controversies in terms of prognostic risk factors of progression and optimal mode of treatment. A total of 32 patients (2 with focal global sclerosis; FGS, the remainder with FSGS) were followed up for a mean period of 82 months (3-240 months). Fourteen presented with nephrotic syndrome and 18 had proteinuria with or without hypertension. Thirteen patients, all of whom except 1 were nephrotic, received steroid treatment with or without other immunosuppressive agents (cyclophosphamide/cyclosporin A/azathioprine). Three of the steroid-treated remained stable in complete remission; 5 nephrotic non-responders had renal death. The mean slope of 1/creatinine versus time for steroid-treated and non-treated groups was -0.23 and -0.043, respectively (p = 0.04), suggesting that nephrotic range proteinuria might be prognostically important. However, for the population of FSGS/FGS as a whole, only the initial serum creatinine predicted renal survival (p = 0.001 by Cox's regression model). Hypertension and hypercholesterolaemia were not important variables by themselves. Nevertheless, we found that the 9 patients treated with antihyperlipidaemics (gemfibrozil/probucol/cholestyramine/maxEPA) fared better, mean slope being -0.023 versus -0.103 for non-treated, though not reaching statistical significance (p = 0.96). Controlled prospective study involving a larger number of patients might be worthwhile.