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Biomedical subjects

A Satta

Publications and source records attributed to A Satta.

At least 37 records · Page 2Linked to original sources

Immunosuppressive treatment of the glomerulonephritis of systemic lupus.

To evaluate the results, the long-term prognosis and the rates of complication of an immunosuppressive regimen with corticosteroids and cyclophosphamide in the treatment of the nephritis of systemic lupus erythematosus, 21 patients with lupus glomerulonephritis were studied. Renal biopsies were performed in 17/21 of them and indicated diffuse proliferative (6 patients), diffuse mesangial (4) and membranous (7) glomerulonephritis. Treatment was structured in 4 phases: 1) induction with methylprednisolone 250 mg i.v. for 7-14 days, and cyclophosphamide 100-200 mg p.o., q.d., or 20 mg/kg i.v. every 28 days; 2) maintenance with prednisone p.o., 2 mg/kg q.o.d. for 45 days, and cyclophosphamide as before; 3) tapering, with reduction of prednisone by 15% each month for 4 months; 4) indefinite maintenance with prednisone slowly tapered to the least effective q.o.d. dose and cyclophosphamide discontinued after six months of treatment. This cycle was repeated in the event of a relapse. After a first immunosuppressive cycle, 20/21 patients achieved remission of glomerulonephritis. Plasma creatinine fell from 97 +/- 6 to 80 +/- 3 microMol/l (p < 0.01). Proteinuria fell from 2.1 +/- 0.4 to 0.2 +/- 0.4 g/d (p < 0.0001) and the nephrotic syndrome, present in 8 patients, disappeared. After an average of 20 +/- 7 months, 8 patients relapsed: all remitted again after a repeat cycle, but 1 later progressed to end-stage renal failure during pregnancy. After an average of 56 months 4 out of these 8 patients relapsed again: 1 progressed to end-stage renal disease following an abortion and 3 remitted completely after a third cycle. Thus, 18 out of 21 patients are presently in remission with an average dose of prednisone of 13.7 mg/day after an average follow-up of 52 +/- 38 months (range 2 to 156). Three patients are presently off treatment. In 16 patients with extended follow-up of 2 to 13 years, anti-nuclear antibodies, anti-DNA antibodies, albuminuria and cylindruria fell below post-cycle levels (p < 0.001 for all). We conclude that intensive immunosuppression with steroids and cyclophosphamide can achieve excellent long-term results in the treatment of systemic lupus with glomerulonephritis.

Adrenal Cortex Hormones↗

Immunosuppressive treatment of membranoproliferative glomerulonephritis.

The treatment of membranoproliferative glomerulonephritis (MPGN) is considered by most authors as unrewarding, and the disease progresses to end-stage renal disease (ESRD). We studied the effectiveness of a new immunosuppressive (IS) regimen by analyzing the rates of remission, relapse and progression to ESRD in 19 patients with MPGN. The treatment consisted of 4 phases: (1) induction with intravenous boluses of methylprednisolone plus cyclophosphamide (CPM) orally; (2) maintenance with oral prednisone (PDN) in an alternate-day regimen and CPM in a daily oral dose; (3) tapering during which PDN alone was slowly decreased; (4) discontinuation when CPM was omitted and PDN slowly withdrawn according to the steroid withdrawal schedule. At the end of the treatment that lasted on average 10 +/- 1 months, 15 patients remitted, 3 improved and 1 progressed. There were 8 relapses in 6 patients: 4 in 3 patients were treated with repeat cycles and remitted completely. Four patients who had relapsed after 4, 8, 11 and 13 years of remission refused retreatment and progressed rapidly to ESRD. All patients treated and retreated after relapsing had remissions, while renal failure and disease progression occurred in 1 patient only. Plasma creatinine averaged, in the whole group, 165 +/- 26 before, 156 +/- 30 after treatment and 224 +/- 57 microM/l at the end of 7.4 +/- 0.8 years of follow-up. An intensive IS regimen combining steroids and alkylating agents in high doses and for a prolonged time is effective in inducing remission and halting progression to ESRD in patients with MPGN.

Adolescent↗

[Ultrasonography diagnosis of medical nephropathies: the clinician's needs].

Echography and echo-color Doppler represents a relatively new tool in the management of patients with renal disease. We report here the flow-chart we currently use to evaluate such patients, and emphasize the role of echography and of echo color Doppler in diagnosing and monitoring medical renal diseases. Besides gaining informations on renal morphology and texture, echo color Doppler provides clinically relevant data on blood flow and vascular resistivity. Changes of these variables are useful in the differential diagnosis between functional and organic acute renal failure. In addition, as histology remains essential in diagnosing parenchimal disease, echography has a role, allowing guided biopsy, safer approach, and monitoring of possible complications. Finally, when diagnosis has been obtained and therapy has been started, echography is useful in monitoring long term changes of size, texture and blood flow.

Humans↗

Quantitative evaluation of the brain electrical activity of patients suffering from chronic obstructive bronchopneumonopathy (COBP).

The authors subjected 66 patients suffering from COBP with chronic respiratory insufficiency (22 with EGA values within standard limits, 44 with irregular PO2 and PCO2 values) to an electroencephalography with BEAM (brain electrical activity mapping). In the absence of clinically noticeable symptoms or neurologic signs of central type, more than 65% of the patients showed an increase of slow activities together with a reduction of the alpha activity presumably imputable only to the respiratory pathology.

Adult↗

Volume receptors in guinea pig labyrinth: relevance with respect to ADH and Na control.

We tested the hypothesis that changes in extracellular fluid volume are reflected by pressure changes within structures of the inner ear and that through neural pathways, a control mechanism exerts an influence on antidiuretic hormone (ADH) release and Na excretion. The study was performed on 35 guinea pigs. In protocol 1, 13 animals were studied before and after decompression of the inner ear by bilateral fluid withdrawal in an experimental setting of sustained isotonic expansion that kept the osmoreceptor partially activated and the intrathoracic volume receptors suppressed. A group of six sham-operated animals served as control. In protocol 2, nine animals were studied before and after a unilateral rise in their inner ear pressure during slightly hypertonic low-rate infusions that kept the osmoreceptor and thoracic volume receptors stimulated. A group of seven sham-operated guinea pigs served as controls. Decompression of the inner ear was attended by a rise in plasma ADH from 11.9 +/- 2.4 to 29.1 +/- 6.9 pg/ml, in urine osmolality (Uosmol) from 470 +/- 48 to 712 +/- 46 mosmol/kg (P less than 0.001), and a fall in urine flow rate (V) from 184 +/- 47 to 71 +/- 11 microliters/min (P less than 0.01), whereas plasma Na (PNa) and osmolality (Posmol) did not change. During inner ear hypertension, plasma ADH fell from 25.6 +/- 3.9 to 18.4 +/- 3.1, Uosmol from 829 +/- 58 to 627 +/- 43 (P less than 0.001), and V rose from 51 +/- 11 to 130 +/- 23 (P less than 0.001), whereas glomerular filtration rate, PNa, and Posmol did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Importance of liver interstitial pressure on sodium retention.

Experiments were performed on 23 dogs to assess the effect of splanchnic pooling on renal hemodynamics and Na retention. When the thoracic duct pressure was raised to 40 cm H2O (HTDP), liver interstitial pressure rose from 9.0 +/- 0.4 to 19.8 +/- 1.1 cm H2O. Simultaneously, glomerular filtration rate (GFR) and renal plasma flow fell in the left kidney from 16.3 +/- 1.7 to 9.6 +/- 1.3 and from 73.7 +/- 12.2 to 44.3 +/- 9.8 ml.min-1, respectively (p less than 0.01). UNa.V fell to 59 +/- 9% of control value (p less than 0.01). Plasma antidiuretic hormone (ADH) rose from 29.5 +/- 7.7 to 46.9 +/- 9.2 pg.ml-1 (p less than 0.05). When a portocaval shunt (PCS) was opened in 10 dogs during HTDP after the first set of experimental measurements, splanchnic pressure fell from 17.2 +/- 1.1 to 11.5 +/- 1.2 cm H2O, attended by a return towards control of GFR. ADH fell significantly to 16.5 +/- 8.1 during PCS, and to 9.7 +/- 1.5 pg.ml-1 during a last, postexperimental control period. Instead, UNa.V remained unchanged at the low levels measured during HTDP alone. When the HTDP was released in the 17 dogs without, and the 10 dogs with PCS, all variables became indistinguishable from control, except for UNa.V, which remained reduced, even in 4 aldosterone-escaped animals. No significant change in any of these variables occurred in 6 sham-operated control animals. These data demonstrate that it is possible to increase interstitial liver pressure through the lymph duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical and functional course of a group of patients with COPD under controlled medical-rehabilitative treatment over a 6-year period].

Functional and clinical tests were performed on a group of 36 patients with COPD for 6 years. During this period they had medical treatment as well as cycles of respiratory rehabilitation (diaphragmatic breathing and exercise training). After this period the resistance to muscular work was greatly enhanced in 9 subjects (25%), enhanced in 25 (69%), little enhanced in 2. Functional respiratory parameters did not change in a significant way, thus indicating the stability of the disease, which did not worsen. One interesting feature was the mean reduction in residual volume (-32%, p less than 0.001). This may indicate that a better coordination of the diaphragm can reduce pulmonary hyperinflation. The ventilatory pattern spontaneously changed towards a stability of ventilation, with increased respiratory frequency and reduced tidal volume.

Breathing Exercises↗

Sodium reabsorption by the Henle loop in humans.

In a previous study, we described a new method [3] to measure Na reabsorption by each segment of the human nephron independently. Reabsorption was expressed as equivalent volumes of solute-free water (CH2O) generated by the loop of Henle (CH2O-HL) and by the distal tubule (CH2O-DT), and dissipated by back diffusion (BD) across collecting ducts (CH2O-BD). These data were obtained during maximal water diuresis (MWD). The present study was undertaken to calculate CH2O-HL by experiments performed during maximal antidiuresis (MA). For this purpose, a new theoretical approach was devised, described by algebraic equations which allowed calculations of segmental transport during MA alone, where only CH2O-HL could be calculated independently. The study was performed on 14 normal volunteers who were studied twice by clearance measurements, firstly during MWD and again during MA. In each experiment, clearance periods were performed during baseline conditions and during the administration of furosemide (0.7 mg/kg bolus injection followed by 0.06 mg/kg/min maintenance infusion). From the values measured during either condition, segmental reabsorption was calculated. During MWD, CH2O-HL averaged 19.4 + 10.4, during MA 20.4 + 8.0 ml/min/GFR X 100; p greater than 0.05. The paired measurements were significantly correlated (r = 0.80; p less than 0.01). These data demonstrate that CH2O-HL obtained with the original theory is a reproducible result that can be confirmed with independent measurements obtained during different experimental conditions. Thus, measurements of segmental Na transport in the human nephron are feasible and can contribute important informations on disease states.

Absorption↗

[Diuretic and antihypertensive activity of azosemide].

The results of a study conducted using a new loop diuretic, Azosemide, on a group of 45 patients suffering from hypertension and oedema are reported. Thirty patients were studied in an open trial and in association with other drugs. The remaining 15 exclusively hypertensive patients, were studied in a controlled trial against Indapamide. The patient's standing and recumbent arterial pressure was monitored and all were given periodic weight checks. In the 1st group, Azosemide brought about a significant reduction in arterial pressure, without modifying body weight, but caused considerable weight loss (from 71 to 64 kg) (P less than 0,01) in the oedema patients without altering arterial pressure. In the 2nd group of hypertensive patients, a significant fall in arterial pressure (from 166 to 138 mmHg) was observed, most notably after Azosemide treatment. None of the patients revealed side effects, or alterations in laboratory parameters. It is therefore suggested that Azosemide--given its effectiveness and ease of application--is particularly useful for the diuretic treatment of hypertensive and oedematous patients.

Body Weight↗

Distal tubular sodium and water resorption in man.

It is possible to quantitatively estimate Na and water transport by each segment of the human nephron during maximal water diuresis (MWD) with a newly developed technique. The present study describes a new development whereby Na reabsorption by the ascending limb of Henle's Loop can be measured during a test of maximal antidiuresis (TMA) and compared with that obtained in separate experiments during MWD. In experiments performed on eight subjects, Henle's Loop reabsorption, expressed as equivalent volume of solute-free water generated, was 23.9 +/- 3.7 during MWD, 24.5 +/- 2.3 ml/min/100 ml GFR in TMA, p greater than 0.05; r = 0.68, p less than 0.05. Thus, our new method is reproducible and theoretically correct.

Absorption↗

Demonstration of action of muzolimine on the serosal side of Henle's loop cells.

Muzolimine, a new diuretic, is known to act by inhibiting Na transport along the ascending limb of Henle's loop. Because of its ineffectiveness when perfused into the lumen, and as a result of experiments on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics. We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats. The animals were anesthetized, both ureters cannulated, and a hydronephrosis established in the left kidney by applying a counterpressure to the ureter, slowly and progressively increased up to 60 cm H2O in 3 minutes and kept stable for 20 minutes. Then either muzolimine 1.2 mg, or furosemide 4 mg, was injected i.v. together with 131I-Hypaque as a glomerular marker. Three minutes later the hydronephrosis was released in the left kidney by cutting the catheter, and urine collections were started simultaneously in both kidneys into 25 microliter glass capillaries, that were filled in continuous sequence and numbered progressively. In each urine sample from each glass capillary Na and 131I-Hypaque were measured. In 5 animals receiving furosemide, UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample. The rise in Na concentration, indicating delivery of urine whose Na reabsorption had been inhibited along the loop of Henle paralleled that in 131I-Hypaque, indicating that the diuretic and the glomerular marker had reached Henle's loop simultaneously, following filtration after the hydronephrosis had been discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevention of acute renal failure by diuretics.

Experiments were performed on 26 rats to evaluate the effect of furosemide and muzolimine in an experimental model of acute renal failure (ARF). After control clearance measurements from both the left and the right kidney, an acute hydronephrosis was produced on the left side only, to completely interrupt urine flow rate. At the 17th minute of stop-flow, placebo (4 animals), furosemide (4 mg i.v. in 5 animals) or muzolimine (1.2 mg i.v. in 5 rats) were injected and three minutes later the renal arteries were clamped bilaterally for 20 minutes. The arterial clamps and the left hydronephrosis were removed at the 20th minute of ischemia and then 5 consecutive clearance periods were performed from either side to assess recovery from post-ischemic ARF. There was no difference in the entity of GFR depression and speed of recovery of either kidney between placebo, muzolimine and furosemide. The left, post-hydronephrotic kidney consistently exhibited a post-ischemic renal function more depressed than that measured in the contralateral side, although the speed of recovery was the same. The ATP content of the renal tissue was significantly larger in the right kidney compared to the contralateral side in the group receiving furosemide. In the animals treated with muzolimine ATP was significantly depressed in both kidneys. In the post-ischemic period the urinary Na excretion and the fractional water excretion rose significantly with either diuretic compared to placebo. However, this did not influence the recovery in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

The role of prostaglandins in Na retention of porta-cava shunted rats.

The importance of prostaglandins (PG) in Na and water retention of liver cirrhosis was studied in rats with porta-cava shunt (PCS) compared to control, non-shunted animals. Balance studies were performed in metabolic cages with diets of high, normal and low Na. An experimental phase, during which the animals received either 5 mg X kg-1 of indomethacin daily or placebo, was preceded by a control period and followed by a post-indomethacin period identical to the control phase. In each diet, indomethacin, but non placebo, caused a positive Na balance, correlated with Na intake, which in overall pooled data amounted to -1453 +/- 255 muEq in PCS rats, significantly larger than that measured in controls, of -295 +/- 320 muEq (P less than 0.01). This was attended by a reverse change in K balance of -35.6 +/- 349 muEq versus -1566 +/- 582 muEq (P less than 0.01); glomerular filtration rate (GRF) was unchanged. These data demonstrate that PGs contribute to the control of Na homeostasis in the presence of PCS.

Animals↗