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Biomedical subjects

F P Schena

Publications and source records attributed to F P Schena.

At least 109 records · Page 6Linked to original sources

Chronic renal failure for bilateral spontaneous kidney rupture in a case of tuberous sclerosis. Case report and review of the literature.

A case of spontaneous, but not contemporary rupture of both kidneys in a 42-year-old man with tuberous sclerosis is described. Despite the high incidence of renal involvement, chronic renal failure due to replacement and compression of renal tissue by hamartomas is rare. We reviewed 25 cases in the literature and found only 1 other case which necessitated maintenance hemodialytic treatment for kidney rupture. It is suggested that early diagnosis and conservative partial nephrectomy could prevent or delay the onset of chronic renal failure, malignant transformation and dramatic rupture of hamartomas.

Adult↗

Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells and expansion of mesangial matrix are common histologic features of proliferative glomerular disease, a frequent cause of renal failure. Proliferation of glomerular mesangial cells occurs in response to platelet-derived growth factor (PDGF), and these cells release PDGF and express PDGF A and B chain mRNAs. However, all studies relating PDGF to potential changes in glomerular structure and function to date have been performed in vitro. To explore the role of PDGF in proliferative glomerulonephritides, we studied the expression of PDGF in vivo in two animal models of IgA nephropathy with different histologic patterns of glomerular injury: either predominant mesangial proliferation or expansion of mesangial matrix. Increased expression of PDGF and PDGF B-chain mRNA in whole kidneys from diseased mice was demonstrated by immunohistochemical techniques and by solution hybridization assay, respectively. Immunohistochemically, PDGF was localized primarily within the mesangial area of glomeruli and to a much lower extent in interstitium. The increased PDGF expression correlated with the degree of hypercellularity and clinical features of the disease. In addition, PDGF expression was increased in some forms of human glomerulonephritis, characterized by mesangial proliferation. These findings suggest that PDGF may be a major contributor to mesangial cell proliferation seen in proliferative glomerulonephritides.

Animals↗

Involvement of peripheral blood monocytes in haemodialysis: in vivo induction of tumour necrosis factor alpha, interleukin 6 and beta 2-microglobulin.

Our aim was to evaluate the role of three different variables in the activation of the monocyte system: dialysis membrane (cuprophane or polyacrylonitrile), dialysate (acetate or bicarbonate), and procedure (standard or high-flux haemodialysis). By ELISA test we measured the 'in vivo' intracellular (monocyte-associated) production and extracellular release of tumour necrosis factor alpha (TNF alpha), interleukin-6 (Il-6) and beta 2-microglobulin (beta 2-M) by monocytes from 20 uraemic patients before and after the dialysis session. At the beginning of the dialysis session, uraemic patients' cultured monocytes spontaneously released a greater amount of TNF alpha, Il-6 and beta 2-M compared to normal controls. However, no differences in cytokine and beta 2-M were observed in monocyte lysate between the two groups. At the end of the dialysis session, cultured monocytes from patients treated with cellulosic membranes and acetate dialysate showed greater TNF alpha values than normal controls (P less than 0.001 and P less than 0.05 respectively). Moreover, TNF alpha and Il-6 values were strictly correlated (P less than 0.05). These results clearly show an activation of the monocyte system in uraemic patients undergoing periodic haemodialysis. The implicated factors may be multiple, such as complement activating cellulosic membranes or acetate dialysate. The production of TNF alpha, Il-6 and beta 2-M may explain some of the pathological findings observed in long-term haemodialysis patients.

Adult↗

[IgA nephropathy. A frequent disease in the Mediterranean area].

Primary IgA nephropathy (IgAN) is a worldwide disease characterized by the recurrence or macroscopic hematuria episodes followed by continuous or intermittent microscopic hematuria. This disease is more frequent in men than in women and the prevalence is higher in the Asian and European areas than Australia and North-America. However the prevalence of IgA is strictly correlated with the biopsy policy and health screening urinary tests. The renal biopsy implicates the diagnostic and prognostic aspects since various histological degrees of renal lesions show different behaviour of the renal function. Even though the disease is progressive in a minority of patients various investigators have attempted treatment with various drugs. Corticosteroids seem to have effect on the course of IgAN in those patients with heavy proteinuria or nephrotic syndrome and normal renal function. Since Berger's original report the immunological mechanisms implicated in the pathogenesis of IgAN have been extensively described. Increased serum levels of IgA, mainly in the polymeric form, and the occurrence of circulating IgA immune complexes which localize in the glomeruli may be explained by an abnormal regulation of the IgA system. The disregulation of IgM-IgA switch may be implicated in this IgA disorder. Recent data have evidenced similar abnormalities in family members.

Adult↗

Effects of an acute protein load on urinary albumin excretion in kidney donors.

In six kidney donors with normal baseline urinary albumin excretion (UAE) we studied the behavior of the UAE after 150 g of a meat protein meal and after a carbohydrate meal of equal caloric (1,370 kcal), water (1 liter) and sodium content (51 mEq). The mean creatinine clearance (Ccr) increased significantly after a protein load at the first (p less than 0.01) and second hour (p less than 0.05), while it did not change after the carbohydrate meal. The mean UAE increased significantly after the protein meal at the first (p less than 0.05) and second hour (p less than 0.05), while after the carbohydrate meal the mean values were increased at the first (p less than 0.05), second (p less than 0.05) and third hour (p less than 0.05). Furthermore, the mean values of UAE after the protein meal were significantly higher (p less than 0.05) than those found at the same time after the carbohydrate meal. Diuresis and natriuresis increased significantly after both meals. These findings show that the increased UAE after the protein meal may be due to a further increase in Ccr in the hyperfiltering remaining kidney, while the smaller increase in the UAE observed after the carbohydrate meal may be due to water load and increased urine flow, which impairs albumin tubular reabsorption. The prognostic importance of microalbuminuria after either meal is therefore uncertain.

Albuminuria↗

A retrospective analysis of the natural history of primary IgA nephropathy worldwide.

The worldwide medical literature was reviewed to determine whether the prevalence, clinical presentation, and immunohistologic findings of primary IgA nephropathy were related to geographic areas. A total of 68 reports containing detailed clinical histories and laboratory findings were analyzed. The selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Analysis of the data showed that IgA nephropathy is more frequent in the Asian area than in Australia, Europe, and North America. The male/female ratio indicates that males are more likely to be affected by the disease, particularly in the second and third decade of life. The appearance of the disease is characterized by microscopic hematuria and mild proteinuria in Asians, whereas gross hematuria is more frequent in American and European patients. At the time of renal biopsy, fixed microscopic hematuria is detected in a high percentage of patients in Asia and Europe, whereas macroscopic hematuria is more frequent in American patients. Mild renal lesions occur more frequently in Asian patients, while severe renal lesions and a high frequency of immunoglobulin and complement deposits are present in American and European patients. Differences encountered in this retrospective analysis may be influenced by two important factors: (1) the absence of urinalysis screening programs in the schools of Europe and North America, and (2) the different approaches to renal biopsy in the eastern and western parts of the world. Due to the high rate of renal insufficiency and end-stage kidney disease in European and North American patients with IgA nephropathy, it is recommended that a program of urinalysis screening in schools and an appropriate renal biopsy policy be adopted in the western areas of the world.

Adult↗

Regional variation in C4 phenotype in patients with IgA nephropathy.

The relationship between complete deficiency for either isotype of the fourth component of complement, C4A or C4B, and glomerulonephritis was initially examined in white patients from Kentucky with either IgA nephropathy or Schönlein-Henoch purpura. Subsequently, C4B deficiency was found to be associated with IgA nephropathy for pediatric patients followed in Cincinnati, Ohio. We later reported that at least 60% of the original patients from Kentucky were related to at least one other patient with the disease. This finding raised the possibility that the C4 phenotype frequencies for these patients may have been biased by the fact that they were based on a sample of related patients. In our study, C4 phenotyping was performed for 52 related and 63 unrelated patients from Kentucky, 81 unrelated patients from the Mid-South region of the United States, and 39 unrelated patients from the Puglia region of southeastern Italy. In addition, data from patients with IgA nephropathy from Spain were available for comparative studies. Neither C4A deficiency nor C4B deficiency was significantly increased for groups of unrelated patients from the Mid-South, Italy, Spain, or Kentucky in comparison with regional control subjects. In fact, C4A and C4B deficiencies did not occur in any of the Italian patients. With the exception of C4A.6, frequencies for the most common C4A and C4B alleles did not differ among the unrelated patient and control groups from Kentucky and the Mid-South. In addition, no significant differences in C4A and C4B allelic frequencies were observed in comparisons of pediatric patients (diagnostic biopsy before age 18 years) and adult patients with IgA nephropathy in either U.S. population. Italian control subjects had a significantly lower frequency for C4A null alleles in comparison with control subjects from both Kentucky and the Mid-South; a significantly higher frequency of C4B null alleles was found among Kentucky control subjects than in Mid-South, Italian, and Spanish control samples. The importance of recognizing the ethnic background of study subjects and of eliciting a good family history to minimize unsuspected sampling of related patients should be considered in future disease association studies.

Adult↗

Meta-analysis of randomised controlled trials in patients with primary IgA nephropathy (Berger's disease).

An overview of the papers published in the last 10 years was performed to evaluate whether treatment with currently available drugs was beneficial in patients with primary IgA nephropathy (IgAN). Eight selected papers involving 196 IgAN patients with moderate or heavy proteinuria, associated in some cases with the nephrotic syndrome, were analysed. The criteria for inclusion were strict, because meta-analysis requires randomised controlled trials with full descriptions. Furthermore, papers were selected in which treatment was performed on IgAN patients with proteinuria, since prognosis is poor in the presence of this sign. The results of statistical analysis show that IgAN patients with heavy proteinuria, whether or not associated with the nephrotic syndrome, benefit from the administration of corticosteroids and/or cytotoxic drugs, as 66.7% of patients had complete or partial remission both in controlled trials and in retrospective studies; renal function also improved in treated patients. In contrast, no beneficial effect was observed in IgAN patients with moderate proteinuria. These results suggest that it is advisable to administer corticosteroids and/or cytotoxic drugs to IgAN patients with heavy proteinuria, irrespective of the association of this condition with the nephrotic syndrome in individual patients.

Adrenal Cortex Hormones↗

Clinicopathological features in patients with isolated C3 mesangial proliferative glomerulonephritis.

The clinicopathological picture of 'isolated C3 mesangial nephritis' was studied in our case records. Focal and segmental or generalised deposits of C3 in the mesangium were found in 12 of 157 (7.6%) patients with primary glomerulonephritis. The clinical picture, similar to Berger's disease, was characterised by episodes of gross haematuria and/or persistent or recurrent microhaematuria and/or proteinuria. Arterial hypertension and mild renal failure were observed in one case. Light-microscopy showed minor glomerular changes such as focal and segmental increase of mesangial matrix and mesangial hyperplasia. During the short-term follow-up (median 25.5 months) no deterioration of renal function was observed. The clinical course and short-term prognosis suggest that this form of glomerulonephritis is benign.

Adolescent↗

Increased production of interleukin-2 and IL-2 receptor in primary IgA nephropathy.

The production of interleukin-2 (IL-2) by peripheral blood mononuclear cells (PBMC) in 13 patients with IgA nephropathy (IgAN) and 9 patients with chronic glomerulonephritis was investigated. Moreover, the distribution of IL-2 receptor (IL-2R) expression was studied in the purified T cell population versus the non-T cell population of IgAN patients. The results show a spontaneous significant production of IL-2 in cultures of PBMC from patients with IgAN (P less than 0.025) that increased after PHA stimulation. IgAN patients also had a significantly higher expression of IL-2R on the surface of PBMC than did patients with chronic glomerulonephritis (P less than 0.05). IL-2R was usually detected on unstimulated purified T cells that expressed the activation DR antigen. Moreover, a high number of DR helper T cells was associated to a reduced number of suppressor T cells (OKT8+M1+). These findings suggest that the increased production of IL-2 in patients with IgAN may be responsible for the increased activity of helper T cells. The high number of IL-2R expressed by freshly separated PBMC implies an in vivo continuous stimulation of these cells, and this finding is in agreement with the demonstrated spontaneous hyperproduction of IL-2. Moreover, the low number of suppressor T cells may contribute to the overactivity of helper T cells bearing IL-2R in IgAN patients.

Adult↗

Effect of fibronectin on C3b and Fc receptor-mediated phagocytosis by peripheral blood monocytes in uraemic patients.

The influence of human fibronectin was evaluated on the phagocytosis in vitro of C. albicans (C3b receptor-mediated) and IgG antibody-coated sheep erythrocytes (Fc receptor-mediated) by the peripheral blood monocytes of 40 uraemic patients undergoing periodic haemodialysis. Some nutritional parameters (albumin, transferrin, C4, C3, haematocrit, lymphocyte count, height and bodyweight) were also evaluated. Results showed significantly decreased plasma fibronectin (P less than 0.001) and reduced C3b receptor (R)- and FcR-mediated phagocytosis in uraemic patients (P less than 0.001). A strict correlation was found between fibronectin and C3bR-mediated phagocytosis (P less than 0.001) and between fibronectin and FcR-mediated phagocytosis (P less than 0.05). In 20 patients with decreased fibronectin concentrations and reduced phagocytic function, the in vitro incubation of peripheral blood monocytes with 50 micrograms/ml of purified fibronectin significantly enhanced C3bR-(P less than 0.001) but not FcR-mediated phagocytosis. Study of nutritional parameters in the uraemic patients revealed that values of fibronectin, C3, IgG and albumin were significantly reduced. Fibronectin correlated significantly (P less than 0.001) with C3. A good relationship (P less than 0.05) was also found between the plasma fibronectin and bodyweight loss. A greater incidence of infectious disease was observed in patients with decreased plasma fibronectin than in uraemic patients with normal values (P less than 0.05). The results suggest that a decrease in plasma fibronectin in uraemic patients could impair the peripheral blood monocyte phagocytic capacity and be potentially dangerous, predisposing the patient to infections. The determination of fibronectin concentration in these patients may, therefore, have a potential value as an indicator of peripheral blood monocyte phagocytic function.

Adult↗

Imbalance of T cell immunoregulatory subsets in primary IgA nephropathy.

The peripheral blood distribution of T cell subsets was evaluated in a group of patients with primary IgA nephropathy (IgAN). Results showed that the frequency of helper (CD4+) and suppressor (CD8+) T lymphocytes in IgAN overlapped that seen in healthy blood donors. In addition, the helper T cell subset (CD4+ CDW29+ and CD4+ CD45R+ cells, respectively) proportion was normal, while with particular reference to suppressor T cell subpopulations, a significant decrease of CD8+ CD11+ lymphocytes (the true suppressor cells) was observed in IgAN. These data were further confirmed by the demonstration that monocyte chemotactic responsiveness triggered by lymphocyte-derived chemotactic factor (LDCF), a lymphokine released by CD8+ CD11- cells, was higher in IgAN than in controls. These data suggest that the low frequency of CD8+ CD11+ cells may be responsible for the impaired T cell immunoregulatory activity in patients with IgAN.

Adult↗

Efficacy and safety of cefotetan in the treatment of complicated urinary tract infections: clinical experience in a selective and single study.

A single, selective study was performed in order to evaluate the efficacy and safety of cefotetan in the treatment of complicated urinary tract infections (UTI). Of 34 pre-treatment isolated strains, 60% were pluri-resistant to other antibiotics (ampicillin, carbenicillin, piperacillin, cefalotin, aztreonam) but only 21.2% to cefotetan. Pseudomonas aeruginosa and enterococci were resistant to cefotetan. Escherichia coli was the common strain isolated (50%). Nineteen adult patients, with complicated UTI caused by sensitive organisms, were treated with a 1 g intramuscular (i.m.) daily dose. Duration of treatment ranged from 5-15 days, with a mean of 13.75 days. Within 24-48 h and 30 days post-therapy, the infection was cured in 84% and 52% of patients, respectively. Reinfection, relapse or super-infection occurred in 42% of the cases. In only one patient, the infecting organism did not respond to treatment. The clinical response was evaluated in only seven patients with symptomatic UTI. Six of them (85.7%) were cured after therapy and the cure persisted at follow-up. In most cases, the adverse reactions were local, mild and negligible. In only 15.8% and 10.5% of patients, side-effects (diarrhoea, headache, abdominal pain, tachycardia, chill, pain and erythema in the injection site) were severe and moderate. In these cases, the adverse reactions were reversible when the therapy was discontinued. The relationship between treatment and side-effects was doubtful in two cases. It is concluded that cefotetan, administered at 1 g i.m. daily dose, is effective in treating complicated UTI caused by sensitive organisms, pluri-resistant to other antibiotics.

Adult↗

Increased serum levels of IgA1-IgG immune complexes and anti-F(ab')2 antibodies in patients with primary IgA nephropathy.

A solid-phase ELISA was used to detect IgA1 immune complexes (IgA1 ICs) containing IgG and IgM in 38 serum samples from 30 patients with primary IgA nephropathy (IgAN) and 14 subjects with non-IgA chronic glomerulonephritis. A jackfruit lectin, jacalin, was used as the substrate for the selective binding of human IgA1 ICs in serum PEG precipitate (7%). The presence of IgG, A and M antibodies against the F(ab')2 region of IgG was also investigated by the solid-phase ELISA. Six patients were studied during remission and relapse (fever, upper respiratory tract infection and macroheamaturia). The results showed significant increases in serum levels of IgA1 ICs (P less than 0.001) in 39.4% of the IgAN patients, IgA1-IgG ICs (P less than 0.001) in 68.4%, and IgA1-IgM ICs (P less than 0.002) in 10.5% of the patients. A significant increase in IgA1-IgG ICs was observed during relapse (P less than 0.02). Significantly high values of IgG (P less than 0.003) and IgA (P less than 0.001) antibodies directed at the F(ab')2 region of IgG were found. A significant increase in anti F(ab')2 antibodies (class IgA and IgM) was seen in the acute phase of the disease. The data suggest that an increased production of IgA1 ICs occurs in IgAN patients; ICs are mainly IgA1-IgG ICs during relapse. The presence of high serum levels of IgG and IgA antibodies against the F(ab')2 region of IgG indicates that in addition to the multiple anomalies of IgA regulation described in IgAN patients there may be further aberrances.

Adolescent↗

Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy.

IgA glomerulonephritis is associated with macromolecules of polymeric IgA in the circulation and mesangial deposits. An impairment in the reticulophagocytic function of patients with IgA nephropathy has been postulated as the potential cause for persistence of IgA immune complexes in the circulation and their eventual glomerular deposition. Since the fate and removal mechanisms of circulating macromolecular IgA are unknown in humans, we examined the blood clearance and organ uptake of purified IgA polymers and macromolecules in patients with IgA nephropathy and normal controls. The IgA macromolecules were prepared by covalent cross-linking of purified human polymeric IgA with a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. After intravenous injection, large IgA molecules were removed rapidly from the circulation of patients (t1/2 = 3.8 +/- 1.0 minutes) and controls (t1/2 = 4.9 +/- 1.5 minutes). Dynamic gamma camera scintigraphy revealed the liver as the major organ that mediated the removal of the macromolecular IgA with no significant difference in the rate of hepatic uptake for patients (t1/2 = 3.4 +/- 0.6 minutes) and controls (t1/2 = 3.3 +/- 0.9 minutes). No significant amount of radioactivity could be detected in the lungs, kidneys, and spleen. The small polymers had a slower and similar clearance rates for patients (t1/2 = 29.3 +/- 7.9 h) and controls (t1/2 = 29.0 +/- 8.6 h). These findings have general significance in showing the liver as a major organ for removal of macromolecular IgA. In addition, the results have specific importance in showing that patients with IgA nephropathy do not suffer from an IgA removal dysfunction.

Adolescent↗

Influence of different dialyzer membranes on plasma fibronectin levels in hemodialyzed patients.

Plasma fibronectin (FN) was assayed in 30 patients with chronic renal failure under conservative therapy, 60 uremic patients undergoing periodic hemodialysis, and 7 patients treated by hemofiltration. Plasma FN was significantly lower in uremic patients on conservative therapy and in those who received intermittent hemodialysis than in the control group. No difference was seen between mean FN concentrations using different dialyzer membranes. Nevertheless, plasma FN levels were significantly higher in subjects after intermittent hemofiltration. There was no evidence of activation of the coagulation system or of any correlation between FN and fibrinogen values. These findings suggest that conventional hemodialysis is not effective in improving the low levels of plasma FN found in uremic patients, whereas intermittent hemofiltration raises FN. These differences may be due to the fact that during hemofiltration, even when using the same dialyzer membranes as in conventional hemodialysis, some "substances" with high molecular weight that could block the synthesis of FN could be removed.

Adult↗