A new approach to the evaluation of hyperphosphatemia in chronic kidney disease.

AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids.

AIM: Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). METHODS: Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or FHD (n=6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. RESULTS: In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/- 0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p<0.01), however, was observed for the 'decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. CONCLUSIONS: Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and 'prediabetic' obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD.

A review of the literature of Bardet-Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty.

Bardet-Biedl syndrome (BBS) is a genetic autosomal-recessive disease (formerly grouped with Laurence-Moon-Biedl syndrome but considered today as a separate entity) characterized by abdominal obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism or hypogenitalism (limited to male patients) and kidney structural abnormalities or functional impairment. The expression and severity of the various clinical BBS features show inter- and intrafamilial variability. This study focuses on three cases of familial BBS--two sisters and one brother (66, 64 and 51 years of age, respectively)--with the main cardinal findings of the disease plus a classic 'metabolic syndrome' (characterized by abdominal obesity, atherogenic dyslipidaemia, raised blood pressure, insulin resistance with or without glucose intolerance, and prothrombotic risk and proinflammatory states). One female patient (not affected by reproductive dysfunction) had three healthy offspring, while the other two patients were unmarried. Another severely affected brother died at 70 years of age; two other brothers are lean but affected by nephropathy, retinopathy, slight mental retardation, polydactyly, hypertension and thrombotic diseases, and had healthy offspring. BBS is a rather rare but severe syndrome that is often mis- or undiagnosed. Ophthalmologists, endocrinologists and nephrologists should be aware of BBS because of its adverse prognosis--early onset of blindness, associated findings of metabolic syndrome and increased vascular risk, and severe renal impairment (the most frequent cause of reduced survival and death early in life).

Rheumatoid syndrome associated with lung interstitial disorder in a dental technician exposed to ceramic silica dust. A case report and critical literature review.

Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.

[Hyperkeratotic Kaposi sarcoma with leg lymphoedema after prolonged corticosteroid therapy for SLE. Case report and review of the literature]. / Sarcoma di Kaposi i ipercheratosico con linfedema della gamba dopo prolungata terapia corticosteroidea per LES. Caso clinico e rassegna della letteratura.

Kaposi sarcoma (KS) is a malignant vascular neoplasia with a viral etiology, characterized by development of multiple hyperpigmentate lesions, primarily at cutaneous level with associated edema and ulcerations, but frequently involving also the mucous membranes and/or visceral organs. In this study, we describe (in the light of the relevant literature) the clinical case of an elderly (78 yrs-old) woman, who developed red-blues multiple hyperkeratotic nodules in the right leg and foot with marked lymphoedema, blushing and pain, after a long period of a low-dose corticosteroid therapy for LES (at least 10 years of continuous treatment). The diagnosis of KS was made on the basis of histologic findings. The patient HLA-typing showed the haplotypes HLA-A2-10, -B21-35, -Bw4-6, -Cw4 and HLA-DR11-13 (some of which are known to predispose to LES, but not to KS). The KS, first described by Moritz Kaposi in 1872, has been a very rare pathology until the 80s, afterwards its frequency has steadly increased, favored by immunosuppressive therapy for autoimmune diseases or tranplants and by immunodepression of AIDS. Concerning the pathogenesis, it is crucial the role of HHV-8 of the herpesvirus family (found in the lesions and in the circulating cells of all KS patients), for which a prevailing sexual transmission is postulated. General physicians and specialists of internal medicine and angiology should know this disease, which can be undiagnosed because of the low incidence in the general population and the consequent poor knowledge of this vascular neoplastic disease, which is now reported with increasing frequency.

Insulin sensitivity of blood glucose versus insulin sensitivity of blood free fatty acids in normal, obese, and obese-diabetic subjects.

We calculated insulin sensitivity indices (ISI) concerning the insulin effect on both glycemia and blood free fatty acids (FFA), named ISI(gly) and ISI(ffa), respectively, in 34 normal, 27 obese, and 11 obese-diabetic subjects by using the following formulas: ISI(gly)= 2/[(INSp x GLYp) +1], and ISI(ffa)= 2/[(INSp x FFAp)+1], in which INSp, GLYp, and FFAp = insulinemic, glycemic, and FFA areas during oral glucose tolerance test (OGTT) (75 g glucose, suggested sampling time: 0, 1, and 2 hours) of the person studied. A slight modification of these formulas allows the calculation of insulin resistance indices (IRI), ie, IRI(gly) and IRI(ffa). ISI and IRI are complementary, as their sum is always equal to 2, so that IRI can be deduced from ISI and vice versa. By using basal levels instead of areas, insulin sensitivity (or resistance) in the basal state can also be measured. Basal levels and areas are expressed by taking the mean normal value as 1, so that in normal subjects ISI(gly) and ISI(ffa), as well as IRI(gly) and IRI(ffa), are always around 1, with maximal variations comprised between 0 and 2. ISI(ffa) was markedly reduced in both the obese (mean, 0.47 +/- 0.04) and the obese-diabetic (mean, 0.41 +/- 0.06) subjects, whereas ISI(gly) was less reduced in the obese (mean, 0.57 +/- 0.04) than in the obese-diabetic (mean, 0.40 +/- 0.03) subjects. ISI(gly)-basal was less affected than ISI(ffa)-basal in both groups. Multiple regression showed that ISI(gly) and ISI(ffa) were significantly inversely correlated with age, body mass index (BMI), and diastolic (but not systolic) blood pressure. Meta-analysis of data from the literature showed that ISI(gly) was significantly correlated with the hyperinsulinemic-euglycemic clamp data. However, the "clamp" is performed under artificial, persistent hyperinsulinemia (which entails FFA suppression) as never occurs in the life of patients, whereas our indices are performed under physiologic conditions, and represent simple tools suitable for clinical or epidemiologic studies, allowing assessment of whole-body insulin sensitivity with regard to both glycemia and blood FFA.

[Bilateral sclerosing lipogranuloma of the gluteal region with calcification. Report of a clinical case and review of the literature]. / Lipogranuloma sclerosante bilaterale delle regioni glutee con calcificazioni. Descrizione di un caso clinico e revisione della letteratura.

A rare case of large bilateral sclerosing lipogranuloma with multiple calcifications of gluteal region is described in an old female patient affected by a cerebrovascular disease. The lesions appeared as firm, nontender, plaques, 9-10 cm in diameter, covered with hyperpigmented skin. This uncommon disorder is discussed on the basis of data obtained from an extensive literature review. The term "sclerosing lipogranuloma" was coined in 1950, and it defines a disease of the subcutaneous fat, which for a trauma or unknown reasons undergoes necrosis of fat cells with the release of fat droplets into intercellular spaces and a peculiar local sclerosing granulomatous reaction of fatty tissue. The cytosteatonecrosis and sclerosing lipogranuloma, post-traumatic or secondary to injection of exogenous oily substances, usually localized in the breast of women and in genitalia of men, are relatively well known. Sclerosing lipogranulomatosis of the orbita and eyelides, an infrequent but severe complication after endonasal surgery, has also been reported. Rarely, the lipogranuloma can be spontaneous or idiopathic or primitive. A particular form of genetic diffuse lipogranulomatosis is the Farber's syndrome, firstly described on 1947. In our patient, the absence of trauma seems to indicate a primitive lipogranuloma. The presence of an acute rheumatic syndrome responsive to corticosteroids, and the positivity of antimitochondrial autoantibodies are in accordance with the report of sclerosing multiple lipogranulomatosis associated with a lupus-like syndrome. Because of the long duration and the absence of acute local symptoms, this syndrome can be considered benign with favorable prognosis, but the physician should know it.

[Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case and review of the literature]. / Psoriasi complicata da grave osteoartropatia psoriasica mutilante. Caso clinico e rassegna della letteratura.

Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.

In vitro inhibition of glucose phosphorylation by an aldose-reductase inhibitor (Tolrestat) in some non-insulin-sensitive rabbit tissues.

We have previously demonstrated that in some non-insulin-sensitive tissues (capillaries of eel swimbladder Rete mirabile, and rabbit eye choroidocapillary lamina, optic nerve, retina, and lens) glucose phosphorylation increases with the increase in the concentration of glucose, a characteristic relevant to the hyperglycemia of diabetes. In the present research we demonstrate an effect of the aldose reductase inhibitor, Tolrestat, on the glucose-phosphorylating activity of rabbit lens and optic nerve, by assaying the enzyme activity of tissue homogenates (in the presence of 10 mmol/L glucose) without or with 10 min preincubation with increasing concentrations of Tolrestat (2, 4, and 8 micromol/L). In the lens, a 18% inhibition (p < 0.01) was observed in the presence of 8 micromol/L Tolrestat. In the optic nerve, a 12% (p < 0.05) and a 21% (p < 0.01) reduction was recorded at 4 and 8 micromol/L Tolrestat, respectively. Significant inverse correlations existed between the concentration of Tolrestat and the phosphorylation rate of glucose of rabbit lens and optic nerve. The dose-dependent inhibition of glucose phosphorylation observed by us suggests that the inhibitory action of Tolrestat on glucose metabolism extends beyond the well-known effects of this compound on the polyol pathway, and might contribute to the refraining action of Tolrestat on the development and progression of late diabetic complications in non-insulin-sensitive tissues.

[A case of idiopathic multiple calcinosis cutis]. / Un caso di calcinosis cutis multipla, idiopatica.

A case of calcinosis cutis, appeared since childhood in a woman 73-years-old, affected by diabetes mellitus with complications, is described. This uncommon disorder is discussed on the basis of data from recent literature. Calcinosis cutis is a condition characterized by the deposition of crystals of calcium phosphate (hydroxyapatite) in the skin. Calcinosis cutis may be idiopathic or secondary. The idiopathic calcinosis cutis is uncommon, may be solitary or multiple, sporadic or associated with Down syndrome (MICC or "milialike idiopathic calcinosis cutis") and appears more often in childhood or adolescence. Secondary calcinosis cutis may appear in the course of juvenile dermatomyositis or in the form of systemic scleroderma named CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangectasia). Calcinosis cutis may also be seen later in the course of renal failure, associated with hyperphosphatemia and secondary hyperparathyroidism. In this case report, calcinosis cutis appeared early in life and the laboratory data showed normal erythrocyte sedimentation rate and leukocyte count, negative LE test and absence of rheumatoid factor and non-organ-specific auto-antibodies, and multiple localizations. On these grounds, the diagnosis of idiopathic multiple calcinosis cutis was made. This is a rare and benign syndrome, which does not cause any late complication and whose prognosis is therefore favourable.

[Alpha-glucosidase and alanine-amino-peptidase in the early diagnosis of renal failure in obstructive jaundice]. / Il ruolo dell'alfa-glucosidasi e dell'alanina-amino-peptidasi nella diagnosi precoce dell'insufficienza renale in corso di ittero ostruttivo.

Renal failure is a serious complication of obstructive jaundice. Early diagnosis and prevention of spontaneous evolution of the disease can improve prognosis, otherwise very poor in many cases. The Authors, on the basis of experimental researches from literature, expose their clinical experience about the validity of the determination of Alpha-Glucosidase and Alanine-Amino-Peptidase for early diagnosis and differentiation between organic or functional forms of renal failure. They conclude that determination of urinary levels of AGS and AAP is a valid aid for the evaluation of renal function in patients with obstructive jaundice.

[Changes in serum levels of folic acid after total gastrectomy]. / Le modificazioni dei livelli sierici di acido folico dopo gastrectomia totale.

The Authors, in consideration that Folic Acid is assimilated in the upper alimentary tract, effected a comparative study between its seric levels in normal patients and in patients submitted to gastrectomy for gastric cancer, at different times from the operation. In the patients of the first group, Folic Acid levels were not correlated with sex, but to age, decreasing with the increasing of it. In gastrectomized patients, serum levels, also if acceptable, were always lower than in control cases, and gradually decreasing with the increasing of the age. The Authors conclude that, obviously, intestinal assimilation and endogenous reserves are able to counterbalance for enough long time the insufficient alimentary absorption.