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Publications and source records attributed to A Pomeranz.
Complications of voiding cystourethrography are infrequent. We report a rare complication of knotting of the catheter within the bladder, necessitating surgical removal of the catheter through the urethra.
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Two infants with biopsy-proven microcystic Finnish congenital nephrotic syndrome (onset at birth) were treated with a combination of captopril and indomethacin for 2 1/2 and 2 years, respectively; they had a marked reduction of urinary protein excretion without further need for albumin infusions. One infant has end-stage renal disease; the other infant's glomerular filtration rate has remained within normal limits.
1. In previous works we have described the development of hypertension and aggravation of proteinuria in rats who became pregnant after the administration of Adriamycin. This was associated with an increase in the glomerular thromboxane B2-prostaglandin E2 ratio. 2. To assess the pathogenetic role of thromboxane in this model, female Wistar rats were mated 2 weeks after receiving Adriamycin (3.5 mg/kg intravenously). Rats were then treated with the thromboxane-receptor antagonist daltroban, 60 mg day-1 kg-1 orally, beginning on day 11 of pregnancy. Systolic blood pressure, proteinuria and the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E2 were measured serially before mating, and on days 14 and 21 of pregnancy. The results were compared with those in Adriamycin-(treated) pregnant rats not treated with daltroban, Adriamycin-treated virgin rats and normal virgin or pregnant rats either treated or untreated with daltroban. 3. In daltroban-treated pregnant and virgin rats treated with Adriamycin, systolic blood pressure remained normal, whereas it increased significantly (P < 0.05) in untreated animals. On day 14, blood pressure was higher in non-daltroban-treated Adriamycin-treated pregnant rats than in non-daltroban-treated Adriamycin-treated virgin rats. Treatment had no effect on blood pressure in normal virgin or pregnant rats. Proteinuria was higher in pregnant rats treated with Adriamycin than in Adriamycin-treated virgin rats, but it was not reduced by daltroban.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: In the presence of pre-existing renal disease, occurrence of hypertension during pregnancy may compromise renal function and aggravate proteinuria. In pregnant rats with early adriamycin nephropathy, this is associated with an increase in the glomerular TxB2:PGE2 ratio. In the present study we evaluated the effect of blood-pressure control on renal function and its relationship with glomerular prostanoid synthesis. DESIGN OF THE STUDY: Pregnant Wistar rats with adriamycin nephropathy received diltiazem, 30 mg/kg/day or methyldopa, 400 mg/kg/day from mid-gestation. Mean arterial pressure (MAP), inulin clearance (CIN), urine protein excretion (UP) and glomerular prostanoid synthesis were measured. Results were compared with (i) untreated pregnant rats with adriamycin nephropathy, (ii) virgin rats with adriamycin nephropathy, and (iii) normal virgin or (iv) pregnant normal rats. RESULTS: MAP increased in untreated pregnant rats with adriamycin nephropathy (P < 0.01 versus virgin rats with adriamycin nephropathy), contrasting with the physiological decrease observed in normal pregnant rats. Diltiazem and methyldopa decreased MAP to normal values. In untreated pregnant rats with adriamycin nephropathy CIN decreased and proteinuria increased significantly at the end of gestation. Treatment with diltiazem and methyldopa augmented GFR, but only diltiazem decreased UP significantly. It was associated with an increased glomerular PGE2 synthesis. CONCLUSION: We conclude that in rats with adriamycin nephropathy, antihypertensive treatment improved GFR. Diltiazem also decreased urinary protein excretion, associated with a normalization of the glomerular TxB2:PGE2 ratio.
BACKGROUND: In rats with incipient adriamycin nephropathy, pregnancy increases urine protein excretion and mean arterial pressure, with no changes in the glomerular filtration rate. Renal histology is normal and the glomerular TxB2/PGE2 ratio is increased. METHODS: In the present study we evaluated the influence of repeated pregnancies on the evolution of adriamycin nephropathy. Two weeks after a first delivery, rats were mated again and were followed till 35 days after the second delivery. RESULTS: In pregnant rats with adriamycin nephropathy, urine protein excretion and mean arterial pressure returned to values identical to those found in age-sex-matched virgin rats with adriamycin nephropathy. At the end of the second pregnancy, mean arterial pressure and urine protein excretion were again elevated, compared with virgin rats with adriamycin nephropathy. Thirty-five days after the second delivery, urine protein excretion and mean arterial pressure remained elevated, 296 +/- 50 mg/day vs 115 +/- 26 and 121 +/- 4 vs 110 +/- 1 mmHg respectively, P < 0.05. Glomerular filtration rate remained unchanged 0.84 +/- 0.09 vs 0.79 +/- 0.09 ml/min in virgin rats with adriamycin nephropathy. The glomerular TxB2/PGE2 ratio was decreased, contrasting with the first pregnancy. At the end of the second pregnancy, histological examination of the kidneys in rats with adriamycin nephropathy revealed a significant increase in mesangial expansion. It was even more marked 35 days later, at the last follow-up, with a semiquantitative score of 162 +/- 29 vs 81 +/- 20 in virgin adriamycin nephropathy rats, P < 0.05. CONCLUSIONS: In rats with adriamycin nephropathy, repetitive pregnancies seem to aggravate the natural course of the disease in an irreversible fashion. The earlier changes in glomerular prostanoid synthesis, particularly on thromboxane, may play a pathogenic role by activating mesangial cell matrix synthesis.
Antiviral activity (AVA) determined by the inhibition of the cytopathic effect (CPE) of vesicular stomatitis virus (VSV) on mice fibroblasts, was measured in the peritoneal effluent of mice. Four groups of animals (each group numbering 30 mice) were studied. Group 1 consisted of sham operated mice and served as the control group. Group 2 underwent implantation of silastic matter (of which the Tenckhoff catheter is made). In group 3, chronic renal failure was induced. Group 4 comprised those mice in which both chronic renal failure was induced and silastic matter implanted. Optical density readings, directly related to the inhibition of CPE were 0.66 +/- 0.01, 0.59 +/- 0.08, 0.85 +/- 0.06 and 0.86 +/- 0.13 for groups 1, 2, 3 and 4, respectively (p < 0.01 for groups 1 and 2 versus 3 and 4). Virus control readings indicative of the CPE of VSV without the presence of peritoneal effluent were 0.58 +/- 0.07, not significantly different from those obtained in groups 1 and 2. They were, however, significantly below values from groups 3 and 4 (p < 0.05). These data show that AVA is undetectable in the peritoneal effluent of normal mice. Chronic renal failure produces an enhancement of AVA. Silastic matter (Tenckhoff catheter) implantation does not play a role in the production of AVA.
In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complication may be related to a diminished synthesis of vasodilatory substances by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To describe an infant with neonatal lupus erythematosus associated with aplastic anemia. SETTING: The pediatric department in a tertiary-care hospital. INTERVENTIONS: Packed red blood cell transfusions and a 3-week course of high-dose steroid therapy. MEASUREMENTS/MAIN RESULTS: The patient presented with severe anemia and a circumscribed, reticular, macular rash on the face and neck at 5 months of age. Skin lesion biopsy revealed epidermic hyperkeratosis, hydropic degeneration of the basal layer, and deposition of immunoglobulins and granular C1q at the dermoepidermal junction. Ro/SS-A antibodies were present in the infant. BFU-E (erythroid progenitor burst-forming unit) colonies in bone marrow increased by about tenfold when suppressor CD8+ T lymphocytes were removed, indicating immune suppression of hematopoiesis. High-dose steroid therapy failed. The infant subsequently developed gram-negative sepsis, severe metabolic acidosis, and consumptive coagulopathy and died. CONCLUSIONS: Neonatal lupus erythematosus may present as part of a spectrum. The disease may range from mild and transient to a severe, life-threatening condition requiring immediate intervention, as in the case reported here. This is the first report of neonatal lupus associated with aplastic anemia due to immune-mediated suppression of hematopoiesis.
Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.
We conducted a randomized prospective multicenter study to compare the safety and efficacy of once daily oral cefixime (8 mg/kg) to twice daily oral trimethoprim/sulfamethoxazole (TMP/SMX) (8/40 mg/kg/day) for the treatment of acute urinary tract infection in children ages 6 months to 13 years. Seventy-six patients (38 in each group) were studied. Thirty-seven percent were younger than 3 years of age. Escherichia coli was the most common isolate in both groups (85%). Eighty-five percent of all Gram-negative organisms were susceptible to TMP/SMX and all were susceptible to cefixime. Seventy-two percent of all patients were febrile at the time of diagnosis. Both groups were treated for 7 to 10 days. Peripheral white blood cell counts, erythrocyte sedimentation rate, body temperature and urinalysis returned to normal at the same rate in both groups. No failures were observed and relapse occurred in 3 cases within the 4 weeks after treatment (2 in the cefixime group and one in the TMP/SMX group). Side effects were observed in 14% of the cefixime group and 16% of the TMP/SMX group and were all mild enough not to necessitate discontinuation of therapy. We conclude that the efficacy and safety of cefixime administered once daily compared favorably with TMP/SMX administered twice daily for acute uncomplicated urinary tract infection.
The influence of pregnancy on the evolution of primary renal disease is still a matter of controversy. Hypertension and derangement of renal function may occur. The pathophysiology of these complications is poorly understood. In the present study, we assessed the influence of pregnancy on the evolution of adriamycin (Adr) nephropathy. Four groups of animals were studied: 1) control virgin rats (C), 2) normal pregnant rats (NP), 3) virgin rats with nephropathy (Adr), and 4) pregnant rats with nephropathy (Adr-P). Inulin clearance measured at the end of pregnancy in awake rats was similar in NP (1.68 +/- 0.20 ml/min) and C (1.39 +/- 0.03 ml/min). In Adr-P rats, it tended to decrease (1.22 +/- 0.7 vs. 1.93 +/- 0.44 ml/min in Adr rats). Mean arterial pressure was increased in Adr-P rats (137 +/- 2.5 vs. 95 +/- 3.2 mmHg in NP; P < 0.001). Urinary protein excretion was 216 +/- 61 mg/day in Adr-P compared with 28.7 +/- 18 mg/day in Adr (P < 0.001). A significant increase in the glomerular thromboxane B2-to-prostaglandin E2 ratio was found in Adr-P rats (1.15 +/- 0.26 vs. 0.52 +/- 0.12 in Adr rats; P < 0.03). In NP rats, no change was observed. Kidneys and placentas were normal on light and electron microscopy. Thus pregnant rats with adriamycin nephropathy developed a clinical picture with several features of preeclampsia. Changes in glomerular prostanoid synthesis might play a role in the development of this complication.
A neonate with primary hyperparathyroidism was successfully managed by conservative medical treatment. This treatment consisted of intravenous saline load, followed by oral rehydration solutions containing between 60-90 mmol/l of sodium. The combined administration of sodium and diuretics maintained normal levels of serum calcium. Similar cases were previously treated by parathyroidectomy with or without autotransplantation. In selected patients, medical treatment should be considered as the initial approach in mild neonatal hyperparathyroidism. It poses no specific risks and offers an alternative to surgical intervention.
Previous studies have shown that administration of captopril to sodium-depleted rats decreases the glomerular filtration rate (GFR) and blunts the increase in glomerular prostacyclin synthesis normally occurring in response to sodium depletion. To clarify the relationship between these two responses, iloprost, a stable analogue of prostacyclin, was administered to Na-depleted, captopril-treated (LNC) rats. At a dosage not affecting systemic blood pressure (12.5 ng/kg/min), iloprost increased GFR in LNC rats by 25% (from 0.26 +/- 0.03 to 0.35 +/- 0.03 ml/min/100 g body wt, P less than 0.01), without significant effects on renal plasma flow. No effect was observed in control rats. The results suggest that altered prostacyclin synthesis could contribute to the decrease of GFR in this model.
Rats made uremic by 2-stage 5/6 nephrectomy and sham-operated control animals were fed either a normal laboratory chow, a high-sucrose (60%) or a high-fat (10% cholesterol; 20% olive oil) diet, all containing 21% protein and identical amounts of electrolytes, vitamins and trace elements. Serum creatinine levels remained unchanged in the control animals but rose in the 5/6 nephrectomised uremic animals by a factor of 2.7 from a mean of 0.44 +/- 0.05 mg/dl to 1.20 +/- 0.11 mg/dl at 8 weeks, without differences between the dietary groups. During 8 weeks of dietary regimen the high-sucrose and high-fat diets induced significant hypertriglyceridemia, generally similar in control and uremic rats. The uremic animals on a high-sucrose and high-fat diet had the most pronounced rise in serum triglycerides, 331.5 +/- 89.0 and 298.0 +/- 45.0 mg/dl, respectively (control: 159.9 +/- 14.0 mg/dl). After 4 and 8 weeks, only the animals on the high-fat diet had significant hypercholesterolemia, most pronounced in the uremic animals (356 +/- 56.3 mg/dl; control: 71.6 +/- 12.9 mg/dl). The animals in the latter group also had significant proteinuria and renal histologic abnormalities consisting of xanthoma-like glomerular lesions, infiltrates and fibrosis not seen in the other groups of animals. These data indicate that dietary-induced hyperlipidemia of short duration causes or aggravates renal damage in the rat with mild-moderate uremia, induced by ablation.
Captopril stimulates glomerular prostaglandin (PG) synthesis and increases glomerular filtration rate (GFR) in Na-repleted rats, whereas, in Na-depleted rats, it fails to stimulate PG synthesis and decreases GFR. In the present work the influence of chronic and acute NaCl loading on PG synthesis and renal function was studied in Na-depleted rats receiving captopril (LNC rats). Glomerular PGE2 and 6-keto-PGF1 alpha were not increased in LNC rats and were significantly lower than in Na-depleted rats (LN). Na repletion, while continuing captopril, increased PG synthesis above control levels. Addition of captopril in vitro to the incubation medium stimulated PGE2 synthesis in glomeruli of control rats, whereas it depressed it in LN rats. Acute loading with NaCl in LNC rats increased inulin and PAH clearances to values significantly greater than in control rats and similar to those of normal rats receiving captopril. Comparable volume loading with isotonic mannitol or 3% albumin increased inulin and PAH clearances only to control values. The specific effect of NaCl in acute loading was prevented by cyclooxygenase inhibition and was not mediated by increased systemic blood pressure. The results provide evidence that the effects of captopril on glomerular PG synthesis and renal function depend on the state of Na balance.
Captopril decreases the glomerular filtration rate (GFR) in Na-depleted rats and inhibits the stimulation of glomerular prostanoid synthesis induced by Na depletion. Because K loading stimulates glomerular prostanoid production in normal rats, we studied the effects of K loading in Na-depleted captopril-treated (LNC) rats. Potassium, but not Cl, loading stimulated the glomerular synthesis of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TxB2). Urinary kallikrein-like activity (UKALLV) and plasma aldosterone increased in K-loaded animals. LNC rats had lower clearances of inulin (CIN) and p-aminohippurate (CPAH) than controls (0.22 +/- 0.02 vs. 0.94 +/- 0.07 and 0.56 +/- 0.12 vs. 2.23 +/- 0.23 ml.min-1.100 g body wt-1, both P less than 0.01). KCl-loaded LNC rats had CIN and CPAH greater than LNC (0.64 +/- 0.16 and 1.90 +/- 0.28 ml.min-1.100 g body wt-1, P less than 0.01). Similar results were observed in LNC rats loaded with a K solution not containing Cl, but not in LNC rats loaded with a mixture of CaCl2, MgCl2, and HCl. In KCl-loaded LNC rats, cyclooxygenase inhibition decreased CIN from 0.49 +/- 0.09 to 0.30 +/- 0.08 ml.min-1.100 g body wt-1 (P less than 0.01). Aprotinin did not affect renal function despite significant decrease of UKALLV. We conclude that K loading prevents the decrease of GFR induced by captopril in Na-depleted rats and that this might be mediated by stimulation of glomerular prostanoid synthesis.
The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases.