Multiple congenital ocular anomalies in three related litters of Jack Russell Terrier puppies.

OBJECTIVE: To describe multiple congenital ocular anomalies in three litters of Jack Russell Terrier puppies. ANIMALS STUDIED: Seven purebred Jack Russell Terrier puppies from three related litters and their four parents. PROCEDURES: Medical records of the puppies and their parents were evaluated. All dogs underwent a complete ophthalmic examination, followed by bilateral ocular ultrasonography in two of the puppies with complete corneal opacity. One eye from an affected puppy was subjected to histopathology. A complete database of pedigrees was built, and individual inbreeding was evaluated. RESULTS: The most commonly diagnosed ocular anomalies in the puppies were: various anomalies of the fundus (12/14 eyes); microphthalmia (10/14 eyes); sclerocornea (8/14 eyes); and persistent pupillary membranes (7/14 eyes). Six out of seven puppies had at least two ocular abnormalities, and only one puppy was normal. Four out of seven puppies had sclerocornea, a particular corneal opacity to date described only in Spanish Podenco dogs. No ocular abnormalities were found in the parents examined (4/4). Analysis of the pedigrees showed that all the puppies and two parents were inbred, and the individual values of the inbreeding puppies were greater than 6.25% in two litters. CONCLUSIONS: Inbreeding with closely related Jack Russell Terriers may result in severe congenital eye abnormalities in puppies.

Surgical management of bilateral, upper and lower eyelid entropion in 27 Shar Pei dogs, using the Stades forced granulation procedure of the upper eyelid only.

Aims: To evaluate the outcome of surgical management of entropion of the upper and lower eyelids in Shar Pei dogs which had previously undergone temporary palpebral tacking, using the Stades forced granulation procedure of the upper eyelid only.Methods: Medical records were retrospectively searched to identify Shar Pei dogs referred for bilateral entropion of both the lower and upper eyelids, and that were treated with the forced granulation procedure of the upper eyelid only. Dogs were included if they had previously undergone unsuccessful temporary palpebral tacking and had at least three follow-up examinations in the 30 days following surgery.Results: Twenty-seven Shar Pei dogs with a median age of 7.9 (min 4, max 24) months were included in the study. Before surgery, all dogs showed signs of severe ocular discomfort with bilateral keratitis and visual deficit due to blepharospasm, enophthalmos and protrusion of the third eyelid. In 13/54 eyes, keratitis was associated with a corneal ulcer. When re-examined 4 weeks after surgery, correction of the upper eyelid entropion and associated trichiasis resolved ocular signs in 50/54 eyes. Mild bilateral lower entropion remained in two dogs postoperatively, which underwent revision surgery with the Hotz-Celsus technique. There were no cases of long-term recurrence of entropion or ocular irritation in the 38 eyes (19 dogs) which were re-examined 1 year after surgery.Conclusion and clinical relevance: The forced granulation procedure performed on the upper eyelid only was effective for correction of entropion in the Shar Pei dogs included in this study. In our experience, it is preferable to operate on the upper eyelid alone, rather than attempting to correct upper and lower entropion during the same surgical operation. The dog can then be reassessed a few weeks later to determine whether the lower entropion is anatomical or secondary to the severe blepharospasm resulting from the painful ocular irritation.

Pharmacokinetics and estimated bioavailability of grapiprant, a novel selective prostaglandin E2 receptor antagonist, after oral administration in fasted and fed dogs.

AIMS: To assess the effect of food intake on the pharmacokinetics of grapiprant administered orally at 2 mg/kg, and to estimate its oral bioavailability in dogs. METHODS: Eight healthy female Labrador Retriever dogs, aged 4-10 years were used. In the initial trial two dogs were administered a 0.5 mg/kg I/V bolus of grapiprant dissolved in ethanol. In the second trial, six dogs were assigned to two treatment groups, using a randomised cross-over design, and received 2 mg/kg of grapiprant orally, as pure powder, after fasting for 12 hours or after being fed. Blood samples were collected at preassigned times up to 36 hours after administration, and concentrations of grapiprant in plasma determined using validated high performance liquid chromatography. RESULTS: After I/V administration in the two dogs the terminal half life was 5.30 and 6.06 hours, clearance was 444 and 476 mL/hours/kg, and volume of distribution was 3,642 and 3,883 mL/kg. Compared with fasted dogs, oral administration in fed dogs resulted in reduced median peak concentrations in plasma (1,598 vs. 614 ng/mL) and delayed median time of peak concentration (1.0 vs. 3.0 hours). The estimated bioavailability in fasted and fed dogs was 111.9 and 59.1%, respectively. Concentrations of grapiprant in plasma following oral administration, in either fed or fasted dogs, remained higher than 164 ng/mL for up to 6 hours. This concentration has been estimated to be the minimal effective concentration required to control pain in dogs. CONCLUSION AND RELEVANCE: Oral administration of 2 mg/kg grapiprant in fed and fasted dogs resulted in different pharmacokinetics of the drug, but did not influence the length of time when concentrations in plasma exceeded theoretical effective concentrations. Further studies are necessary to verify these findings using pharmacokinetic-pharmacodynamic studies and in clinical subjects.

Assessment of habitual physical activity and energy expenditure in dialysis patients and relationships to nutritional parameters.

BACKGROUND AND AIM: Assessment of physical activity level and of energy expenditure is important in the clinical and nutritional care of dialysis patients, but it is not so easy to accomplish. The SenseWear™ Armband (SWA) is a novel multisensory device that is worn on the upper arm and collects a variety of physiologic data related to physical activity. Thus, duration and intensity of physical activity is recorded and expressed as METs (Metabolic Equivalent Task), and energy expenditure is estimated. The aim of our study was to assess interdialytic spontaneous physical activity in stable chronic hemodialysis (HD) patients and the relation to nutritional status and dietary nutrient intake. PATIENTS AND METHODS: In 50 stable patients on maintenance hemodialysis treatment and 33 normal subjects (control group), level of spontaneous physical activity and estimated daily energy expenditure was assessed by SWA and related to biochemistry and anthropometry data, bioelectric impedance vector analysis, and energy and nutrient intake information coming from a 3-day food recall. RESULTS: In respect to controls, HD patients showed lower mean daily METs value (1.3 ± 0.3 vs. 1.5 ± 0.2, p < 0.01), a lower time spent on activities > 3 METs (89 ± 85 vs. 143 ± 104 min/day, p < 0.05), lower number of steps per day (5,584 ± 3,734 vs. 11,735 ± 5,130, p < 0.001), resulting in a lower estimated energy expenditure (2,190 ± 629 vs. 2,462 ± 443 Kcal/day, p < 0.05). 31 out of the 50 HD patients (62%) had a mean daily value < 1.4 METs and hence were defined as sedentary. They differed from the active patients for higher age (63 ± 12 vs. 54 ± 12 y, p < 0.01), lower energy intake (26.1 ± 6.4 vs. 32.4 ± 11.3 Kcal/day, p < 0.05) and lower phase angle (5.5 ± 1.0 vs. 6.3 ± 0.9, p < 0.05). SWA-based estimation of daily energy expenditure was negatively related to age (r = -0.31, p < 0.05), whereas positive relations were observed with BMI (r = 0.51, p < 0.001), phase angle (r = 0.40, p < 0.01), serum phosphate (r = 0.49, p < 0.001) and albumin (r = 0.41, p < 0.01). The mean daily METs values were strongly related to normalized energy intake (r = 0.47, p < 0.001) and also to protein intake (r = 0.33, p < 0.05) and to phase angle (r = 0.38, p < 0.01). Multiple regression analysis showed that energy intake and dietary protein intake were independently related to the intensity of physical activity. CONCLUSION: Our findings indicate that poor physical activity is highly prevalent in stable dialysis patients even when free from physical or neurological disabilities or severe comorbid conditions. The level and intensity of physical activity is positively related to body composition and to dietary nutrient intake. This confirms the strong interrelationship between exercise and nutrition, which in turn are associated with survival, rehabilitation and quality of life in dialysis patients.

Presurgical setting of secondary hyperparathyroidism using high-resolution sonography and color Doppler.

PURPOSE: High-resolution sonography (US) with color Doppler imaging (CDI) is a simple, noninvasive, safe and repeatable technique able to highlight the presence of hyperplastic parathyroid glands and changes in their volume, structure, and vascularization during uremia. The primary aim of this study was to assess the diagnostic accuracy of US and the sensitivity for localizing parathyroid glands with a volume ≥ 500 mm(3). The secondary aim was to assess the parameters that define parathyroid glandular perfusion. MATERIALS AND METHODS: The diagnostic use of US was assessed in 40 consecutive uremic patients with severe secondary hyperparathyroidism (sHPT) who were receiving maintenance hemodialysis or conservative therapy with a hypoproteic-hypophosphoric diet and had undergone parathyroidectomy. Prior to surgery (99m)TC-sestamibi scintigraphy (SM) was performed in all patients. RESULTS: The sensitivity, specificity, positive predictive value and accuracy of US were 74 %, 75 %, 98 %, and 74 %, respectively. The sensitivity for localizing glands with a volume ≥ 500 mm(3) was 90 %. US and SM had a combined sensitivity of 83 %. The vascularization of parathyroid glands became more evident with increasing glandular volume. With CDI, the signs of hypervascularization (i. e. an enlarged feeding artery at the hilum, a peripheral arc of vascularity and/or ray-like endonodular vessels) were present in 77 % of glands with a volume ≥ 500 mm(3). CONCLUSION: The sensitivity of US is higher than that of SM, but it cannot be compared with that of parathyroidectomy (74 vs. 95 %). However, US/CDI is able to characterize glands with different volumes and vascular patterns. Since glandular volume and vascularization are indicative of the severity of sHPT, this study suggests that the main role of US/CDI in the setting of sHPT should be to complete the diagnosis and to evaluate the morphological changes of enlarged glands during uremia in order to define surgical timing, rather than to assess the presurgical location of glands.

Food intake and nutritional status in stable hemodialysis patients.

This is a cross-sectional, multicenter, controlled study aiming to evaluate changes of actual dietary nutrient intake in 94 stable hemodialysis patients in respect to 52 normal subjects and guideline recommendations, and to assess the prevalence of signs of malnutrition. Energy and nutrients intake assessment was obtained by a three-day period food recall. Anthropometric and biochemical parameters of nutrition, bioelectric impedance vector analysis, and subjective global assessment (SGA) have been performed to assess nutritional status. SGA-B was scored in 5% of the patients. Body mass index < 20 Kg/m(2), serum albumin <35 g/L, nPNA < 1.0 g/Kg, and phase angle <4.0 degrees were detected in 16.3%, 16%, 23%, and 8.0 % of patients, respectively. HD patients showed a lower energy and protein intake in respect to controls, but no difference occurred when normalized per ideal body weight (29.3 +/- 8.4 vs. 29.5 +/- 8.4 Kcal/Kg i.b.w./d and 1.08 +/- 0.35 vs. 1.12 +/- 0.32 Kcal/Kg i.b.w. /d, respectively). Age was the only parameter that inversely correlates with energy (r = -0.35, p < 0.001) and protein intake (r = -0.34, p < 0.001). This study shows that in stable dialysis patients, abnormalities of nutritional parameters are less prevalent than expected by analysis of dietary food intake. Age is the best predictor of energy and protein intake in the dialysis patients who ate less than normal people, but no difference emerged when energy and protein intakes were normalized for body weight. These results recall the attention for individual dietetic counseling in HD patients, and also for a critical re-evaluation of their dietary protein and energy requirements.

Adenosquamous Carcinoma of the Upper Eyelid in a Dog.

A 12-year-old, male mongrel dog was presented for a 6-month history of a progressive eyelid mass of the right upper eyelid. The dog's medical history reported long-term bilateral topical application of 0.03% tacrolimus ophthalmic ointment for third eyelid plasmoma and treatment cycles with systemic corticosteroids for a long-standing atopic dermatitis. Complete physical and ophthalmologic examination of the dog as well as complete blood count, serum biochemical analysis, urinalysis, thoracic radiographs, and abdominal ultrasonography were performed. The mass involved the skin and the margin of the upper eyelid, which was ulcerated. Conjunctival hyperemia, and the thickening and partial depigmentation of the third eyelid due to plasmoma were present. The plasmoma was observed bilaterally. Histological examination of the eyelid mass showed an invasive proliferation of malignant epithelial cells with intermixing of both adenocarcinomatous and malignant squamous cell components. An eyelid adenosquamous carcinoma was diagnosed. To the best of the authors' knowledge, this is the first report on an adenosquamous carcinoma of the eyelid in a dog. Immunosuppression has been found to be a significant clinical risk factor for cutaneous adenosquamous carcinoma in humans and was considered a possible risk factor for this dog.

Insulin resistance and low urinary citrate excretion in calcium stone formers.

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no difference was detected as far as urinary oxalate, calcium, uric acid, phosphate, and urine pH and urine volume output were concerned. HOMA-IR values were positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19, p<0.05). This study shows that a higher level of insulin resistance is associated with lower urinary citrate excretion, and that hypocitraturic patients show a greater insulin resistance than normocitraturic calcium stone formers. This may be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports, which have been described in insulin resistance. In conclusion, insulin resistance may contribute to an increased risk of calcium stone formation by lowering urinary citrate excretion. This finding suggests the need for a careful metabolic assessment in patients known to form calcium stones in order to ensure stone recurrence prevention and cardiovascular protection.

Temporal horizontal H-figure sliding skin flap for central eyelid reconstructive surgery in dogs: a retrospective study.

OBJECTIVE: To describe a modified H-figure sliding skin flap for treating eyelid central neoplasms and to evaluate the cosmetic and functional results of this reconstructive blepharoplasty. MATERIAL AND METHODS: Eight dogs affected by eyelid neoplasia involving more than one-third of the central part of the margin underwent an en bloc rectangular surgical removal of the neoplasia. Reconstructive surgery was performed using a temporal horizontal H-figure sliding skin flap. RESULTS: At short-term follow-up visits, seven dogs showed no signs of ocular discomfort, whilst one exhibited mild blepharospasm and ocular discharge associated with partial necrosis of the flap. At the 60-day follow-up, all dogs showed good eyelid margin reconstruction and no signs of lagophthalmos or ocular discomfort. Secondary trichiasis was observed in one dog. CLINICAL SIGNIFICANCE: The procedure allowed a well-positioned, fully mobile eyelid. The secondary trichiasis observed in one dog did not cause evident ocular discomfort at 6-month follow-up.

Safety and effects on the lipid and C-reactive protein plasma concentration of the association of ezetimibe plus atorvastatin in renal transplant patients treated by cyclosporine-A: a pilot study.

Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.

[Historical Archives of Italian Nephrology: Sergio Giovannetti (1924-2000): A distinguished representative of the School of Pisa]. / Archivi storici della Nefrologia Italiana. Un eminente rappresentante della Scuola di Pisa: Sergio Giovannetti (1924-2000).

Sergio Giovannetti (1924-2000) was one the most outstanding representatives of the Pisa School, which developed in the middle of the '60s thanks to the charismatic action of Gabriele Monasterio (1903-1972). Giovannetti's main contributions to the development of nephrology were as follows: - With Quirino Maggiore he outlined a low-protein diet of high biological value--adopted worldwide for many years--for those patients affected by advanced chronic renal failure. - He investigated the role and importance of uremic toxins (particularly methylguanidine) in renal failure. - He outlined a low-protein diet with low phosphorus supply, supplemented with essential amino acids and ketoanalogues, aiming at reducing the progression of chronic renal failure. Finally Giovannetti helped nephrology working as co-editor (together with Geoffrey M. Berlyne), of the journal 'Nephron' for 27 years. He was also the organizer of the 24 th Congress of the Italian Society of Nephrology in Pisa, in 1993.

Keratoconjunctivitis sicca exacerbation in a dog treated with systemic atenolol.

A 6-year-old, intact, male English cocker spaniel was referred for treatment of chronic conjunctivitis and unilateral keratitis. The dog was diagnosed with bilateral immune-mediated keratoconjunctivitis sicca, treated with topical cyclosporine 0·2% ointment and sodium hyaluronate eye drops and improved considerably. After 2 months, pulmonic stenosis was diagnosed, and the dog commenced treatment with oral atenolol; the ophthalmological disease worsened dramatically within a few days. The ophthalmic signs rapidly improved after discontinuation of atenolol, and there was bilateral complete remission after 3 weeks. No oral ß-blocker therapy was reintroduced, and thereafter, keratoconjunctivitis sicca was well-controlled with topical therapy.

Conjunctival myxoma in a dog: clinical and histopathological features.

CASE REPORT: A 9-year-old male Bull Terrier was presented for a 3-month history of a progressive, non-painful conjunctival mass of the right eye. The mass was exophytic and located in the temporal bulbar conjunctiva. No adhesion to the sclera was detected. A presumptive clinical diagnosis of a conjunctival neoplasia was made. Complete physical and ophthalmological examinations of the dog, as well as complete blood count, serum biochemical analysis, urinalysis, thoracic radiography, echocardiography and abdominal ultrasonography, were performed. The mass was surgically removed and a double freeze-thaw cycle of cryotherapy was performed locally. Histological examination of the removed tissue showed a well-delineated, non-encapsulated mass composed of spindle cells in loose myxomatous stroma. No nuclear atypia was observed in the tumour cells. A positive Alcian blue stain confirmed the mucin origin of the stroma. Tumour cells stained positive on immunohistochemistry for vimentin and negative for cytokeratins. A diagnosis was made of conjunctival myxoma. No evidence of local recurrence or distant metastases was identified during the 24-month follow-up period. CONCLUSION: To the best of the authors' knowledge, this is the first report on a conjunctival myxoma in dogs.

Cardiovascular risk factors in severe chronic renal failure: the role of dietary treatment.

BACKGROUND: Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF). METHODS: Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid. RESULTS: Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p < 0.005) with a reduction of LDL cholesterol (p < 0.01) and an increase of apoA1/apoB ratio (p < 0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p < 0.05) with lower TBARS concentrations (p < 0.01) and a significant reduction of total homocysteine (p < 0.002), Lp(a) (p < 0.002) and CRP levels (p < 0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p < 0.001) and OxLDL (p < 0.006) were associated to a risk of CRP > 0.3 mg/dl. CONCLUSIONS: These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Restricted phosphorus and nitrogen intake to slow the progression of chronic renal failure: a controlled trial.

Twenty chronically azotemic patients (experimental group) with a mean creatinine clearance of 22.5 +/- 9.4 ml/min followed a diet supplying daily, per kilogram of body weight, 7.0 mg of phosphorus and 0.5 g of protein, mostly of high biological value, for 11.3 months. A group of 19 similar patients (control group) followed a diet supplying daily, per kilogram of body weight, 12 mg of phosphorus and 0.8 g of protein for a similar period of time. In the experimental group, the serum inorganic phosphorus, urea, and iPTH (both N-terminal and C-terminal fragments) decreased significantly. The creatinine clearance decreased by -0.59 +/- 0.7 ml/min per month prior to the commencement of the experimental diet and increased by a mean of 0.1 +/- 0.4 ml/min per month during the period of study. In the control group, the serum inorganic phosphorus increased, the serum urea and iPTH remained practically constant, and the mean creatinine clearance continued to decrease at a rate not significantly different from that prior to the onset of the study (-0.50 +/- 0.66 and -0.44 +/- 0.10 ml/min per month, respectively). The mechanisms by which the low-phosphorus, low-nitrogen diet slows the progression of renal failure are discussed, and the practical importance of prescribing the dietetic restriction early in the course of renal disease is stressed.

Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells.

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.

Color-Doppler in the imaging work-up of primary hyperparathyroidism.

Primary hyperparathyroidism (PHP) is a rare disease that must be suspected in all the cases of recurrent calcium nephrolithiasis, and that may be totally corrected by surgery. The imaging techniques permit to locate the hyperplastic gland or adenoma before intervention, but their usefulness in patients without a history of previous neck surgery is still debated. Several imaging techniques have been proposed with the aim of locating parathyroid hyperfunctioning glands, including high resolution sonography (US) with color-Doppler (CD), scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). We report here a case of recurrent calcium oxalate nephrolithiasis sustained by PHP, which demonstrates how US coupled with CD and echocontrast enhancement is useful in the preoperative location of parathyroid glands. US is the first choice technique in the evaluation of PHP because it is less expensive and useful in detailing lesions of the neck when carried out by a skilled operator. CD should be regarded as a useful complement of US enhancing its sensitivity (80 vs 90%) especially in the cases of associated thyroid gland diseases. Tc-99m SESTAMIBI scintigraphy coupled with MRI is mandatory in high risk surgical patients, namely in those undergoing repeated neck surgery. In conclusion, considering that surgeon must explore all the four parathyroid glands (because of the possibility of multiple adenomas or hyperplasia) a well definite location of the adenomatous lesion may reduce the risks and the time of intervention, and allow the use of alternative procedures, such as videoscopic surgery. On this view and in terms of economy, only US and CD coupled with Tc-99 SESTAMIBI scintigraphy should be considered before surgery.

Serum uric acid in mild essential hypertension.

The mean serum level of urate and the incidence of hyperuricemia have been found to be normal in 85 patients with untreated essential arterial hypertension without renal failure. On the contrary, the incidence of hyperuricemia has been found to be high in 36 similar patients on a low salt diet and in 19 others who received diuretics. Uricemia decreased in 55 patients on a low salt diet who received hydrazinophthalazine (hydralazine) and in 10 other patients who changed their diet from a low salt diet to a diet supplying normal amounts of salt. These results indicate that essential arterial hypertension does not cause hyperuricemia.

Nutritional treatment of renal failure in type 1 diabetic nephropathy.

This study reports the effects of a low-protein, low-phosphorus, supplemented diet in 8 type 1 diabetics with renal failure. The rate of decline of creatinine clearance, the changes of the urinary protein loss, of total serum protein, of the daily insulin requirement, of the nutritional status and of some hormonal derangements were examined. The rate of decline of creatinine clearance decreased from 1.38 +/- 0.27 ml/min/month during a previous 15.9-month period of unrestricted protein diet, to 0.03 +/- 0.37 ml/min/month during the 17.4 months on supplemented diet. Urinary protein loss significantly decreased, and total serum protein increased. The daily insulin requirement decreased and no deterioration of the nutritional status occurred. Secondary hyperparathyroidism was partially reversed and the mild hypothyroidism corrected. A restricted protein and phosphorus diet supplemented with essential amino acids and ketoanalogs seems to exert several beneficial and no unwanted side effects in type 1 diabetics with renal failure.

The decline of renal function slowed by very low phosphorus intake in chronic renal patients following a low nitrogen diet.

The rate of progression of renal failure has been evaluated in two homogenous groups of chronic renal patients with early insufficiency. In both groups the diet supplied the same amount of calories (approximately 35 Kcal/kg/day) and the protein intake was equally restricted (approximately, 0.6 g/kg/day); however, in Group 1 the phosphorus intake was lower (6.5 mg/kg/day) than in Group 2 (12 mg/kg/day). In both groups the rate of decline of creatinine clearance decreased when patients changed from a free mixed diet to the specially controlled diets, but in Group 1 (lower phosphorus intake) this change was much more marked than in Group 2. Elevated mean levels of serum phosphate and of urinary output of phosphate per unit of creatinine clearance, and elevated mean levels of serum iPTH were found in the patients of Group 2, whereas Group 1 patients had normal mean levels of serum phosphate and of iPTH, and the phosphaturia per unit of creatinine clearance was almost normal. The role of such abnormalities in urinary and serum phosphate, and of secondary hyperparathyroidism, on the progression of renal failure is discussed.