Adherence to the Mediterranean Diet Improves Fatty Acids Profile in Pediatric Patients with Idiopathic Nephrotic Syndrome.

The fatty acid profiles of patients with idiopathic nephrotic syndrome (INS) are different from that of healthy controls, even during remission, revealing an increase of the pro-inflammatory omega 6 series. It is still unknown whether the concomitance of nephrotic syndrome affects the potential positive effects of the Mediterranean diet on the levels of omega 3 and 6 fatty acids. We performed a cross-sectional study to evaluate the association between the adherence to the Mediterranean diet and fatty acid profile in 54 children with INS. The dietary habits were assessed through the validated Kidmed questionnaire. Patients with higher adherence had lower levels of linoleic acid and total omega-6. Moreover, a negative correlation between proteinuria and the anti-inflammatory omega-3 series was found. In conclusion, patients with INS with proteinuria and low adherence to the Mediterranean diet have an imbalance in the omega-6/omega-3 ratio that may benefit from following the Mediterranean diet.

R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria.

An association between the R990G polymorphism of the CaSR gene, coding for calcium-sensing receptor, and primary hypercalciuria was found in kidney stone formers. To confirm this relationship, we investigated hypercalciuric women without stones and studied the effect of CaSR gene in human embryonic kidney cells (HEK-293). We genotyped for CaSR A986S, R990G, and Q1011E polymorphisms, 119 normocalciuric and 124 hypercalciuric women with negative history of kidney stones. Homozygous (n=2) or heterozygous (n=21) women for the 990G allele considered as one group had an increased risk to be hypercalciuric (odds ratio=5.2; P=0.001) and higher calcium excretion (P=0.005) in comparison with homozygous women for the 990R allele (n=220). HEK-293 cells were transfected with the variant allele at the three CaSR gene polymorphisms and with the most common allele with no variants. The transient increment of intracellular calcium caused by the stepwise increase of extracellular calcium was evaluated in stable transfected cells loaded with fura-2 AM. The extracellular calcium concentration producing the half-maximal intracellular calcium response was lower in HEK-293 cells transfected with the 990G allele than in those transfected with the wild-type allele (P=0.0001). Our findings indicate that R990G polymorphism results in a gain-of-function of the calcium-sensing receptor and increased susceptibility to primary hypercalciuria.

R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) shows a great variability in clinical course and severity. Data concerning the association between polymorphic variants of the gene encoding the calcium-sensing receptor (CaSR) and clinical characteristics of PHPT are not conclusive. OBJECTIVE: To evaluate the frequency of three polymorphisms; A986S, R990G, and Q1011E of CaSR in patients with PHPT and to correlate the genotypes with clinical and biochemical parameters. PATIENTS AND METHODS: The study included 94 consecutive unrelated patients referred to our Departments for PHPT diagnosis and management between 2000 and 2005 and 137 age and sex-matched healthy subjects. Patients and controls were genotyped according to standard procedures. Due to the rarity of 990G allele, homozygous and heterozygous subjects were grouped in R/G+G/G set. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications. RESULTS: The proportion of CaSRvariants was similar in PHPT patients and controls. In PHPT patients, only R990G polymorphism was associated with disease parameters; in comparison with R/R, R/G+G/G patients showed lower mean serum parathyroid hormone (PTH) and phosphate levels (139.9 +/- 62.2 vs 199.9 +/- 136.3 pg/ml, P < 0.05 and 0.69 +/- 0.12 vs 0.81 +/- 0.18 mmol/l, P = 0.031 respectively), higher mean 24-h urine calcium concentration and calcium excretion (9.05 +/- 2.05 vs 6.77 +/- 4.31 mmol/24 h, P = 0.012 and 67 +/- 20 vs 51 +/- 26 mumol/l GF, P = 0.039), and increased prevalence of nephrolithiasis (90.0 vs 44.2%, P = 0.007). CONCLUSIONS: The study showed that patients with PHPT, bearing the 990G allele, had lower serum PTH levels and higher urinary calcium excretion in comparison with the other genotype, suggesting an increased sensitivityof the variant receptor to extracellular calcium. Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease.

[Evaluation of the contribution of the importance of neuroimaging for the diagnostics of dementias--comparison to the psychological diagnostics]. / Evaluation des Beitrages der radiologischen bildgebenden Diagnostik bei demenziellen Erkrankungen--ein Vergleich mit der psychologischen Diagnostik.

OBJECTIVE: While psychology is accepted as a necessary component of the dementia diagnostics, the extended clinical diagnostics with neuroimaging is differently estimated. The goal of the study is the quantification of the individual contribution of the two different methods. METHODS: Of 100 patients the diagnosis of entrance, the neurological, the psychological, and the final clinical diagnosis were documented. For both imaging and psychology the sensitivity, specificity, and the positive predictive value were computed. The diagnostic of each method was determined from the change of the final in relation to the initial clinical diagnosis. The neuroradiological investigation took place with MRI, the psychological examination used both usual power and special speed tests. RESULTS: The extended clinical diagnostics led for 26 % of the patients to the change of the clinical diagnosis. Imaging and psychology supplied different own but supplementing contributions. In the case of annihilation imaging contributed with 73.3 %, psychology with 54.1 % to the diagnosis of a neurodegenerative dementia, whereas the contributions to the diagnosis of a vascular dementia were 83.3 % and 70.8 %, respectively. However psychology diagnosed and quantified the dementia. The contribution of neuroimaging consisted in the differential diagnosis of the dementias. Organic causes of symptomatic dementias and vascular encephalopathy without dementia but with consequences for a secondary prophylaxis were additional information also. CONCLUSION: Psychology improves the diagnostic accuracy of dementias. Neuroimaging improves the differential diagnosis of dementias and supplies additional clinically relevant findings. In the qualified diagnostics and differential diagnostics of the dementias both methods are indispensable.

[Is there a referral bias in the diagnoses of patients of a memory clinic?]. / Unterscheiden sich die Diagnosen der Patienten einer Gedächtnisambulanz nach dem Uberweisungsmodus?

In a recent study addressing the contribution of neuropsychology and neuroradiology to the improvement of the dementia diagnoses of a memory clinic more than 45% of the patients (45 out of 101) did not meet the criteria for dementia. This finding was unexpected because all patients had been referred for the diagnosis and differential diagnosis of dementia. The aim of the present study was to examine whether the proportion of nondemented patients varies with the "modus of referral". This was not found to be true. The frequency of the diagnosis "no dementia" was not significantly different for the two patient groups "general practitioner" vs. "neuropsychiatrist" referred patients (p=0.859). In conclusion, there is no difference between the two groups of physicians in the reliability judging whether a "cognitive complainer" needs to be referred to a specialized memory clinic.

Phenotypic variability in Bartter syndrome type I.

Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria, but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.

Therapeutic jaw exercises and interocclusal appliance therapy. A comparison between two common treatments of temporomandibular disorders.

From a total of 1344 consecutive patients referred to a TMD clinic, twenty-six patients fulfilled the strict inclusion criterias of TMD of mainly muscular origin. Half of the patients were assigned to receive treatment with an interocclusal appliance, the treatment being performed by a dentist. The other half was instructed to perform individualized therapeutic jaw exercises, and this treatment was managed by a dental assistant. The treatment result was evaluated after six months. The two treatments had a positive and equal effect upon both signs and symptoms of TMD. A further follow-up by questionnaire one to four years after the final clinical examination showed a lasting treatment result in most patients. Many patients, however, continued to perform jaw exercises and/or to wear their appliances. This indicates that these two treatments are mostly symptomatic and not causal. The conclusion of the present investigation is that therapeutic jaw exercises, managed by a dentist or a dental assistant, is a cost effective treatment with a prognosis comparable to a treatment with an interocclusal appliance and can thus be recommended as the first therapy of choice in patients with TMD of mainly muscular origin.

Effect of atrial natriuretic factor and fate of cyclic-guanosine-monophosphate in the rat kidney.

The mechanisms whereby atrial natriuretic factor (ANF) induces natriuresis are not clarified. Here, the effects of ANF and the cGMP analogue, 8-bromo-cGMP, on Na+, K(+)-ATPase activity in microdissected segments from rat medullary thick ascending limb of Henle (TAL) were evaluated. ANF-induced cGMP accumulation and the cellular handling of intracellularly produced cGMP were also investigated, by measuring the accumulation of extracellular cGMP in suspensions of tubules from outer medulla, enriched in TAL, and of isolated glomeruli. ANF dose-dependently inhibited Na+, K(+)-ATPase activity in isolated TAL in a parallel fashion with increasing cGMP accumulation in OM tubules. For both parameters, pharmacological concentrations (> or = 10(-6) M) of ANF were needed to induce a significant effect. 8-Bromo-cGMP mimicked the inhibitory effect of ANF. The increase in the intracellular cGMP level in response to ANF was dose-dependently reflected in the extracellular level. This finding contrasted with that in the glomerular preparation, where cGMP in response to ANF accumulated entirely intracellularly. Also in glomeruli, high (> or = 10(-6) M) concentrations of ANF were needed to induce a significant effect on cGMP accumulation. In conclusion, ANF inhibited Na+, K(+)-ATPase activity in TAL and the effect was mimicked by 8-bromo-cGMP. cGMP, produced in response to ANF, was extruded from the tubular epithelial cells, but not from glomeruli.

Assessment of local sympathetic function in patients with erectile dysfunction.

Fifty men with erectile dysfunction (ED) were urologically investigated for autonomic deficit by evaluation of the sympathetic skin response at the penis. They were additionally subjected to thorough urological, vascular, psychiatric and neurological examinations, and well-established neurophysiological tests of the somatosensory, sympathetic, and parasympathetic function. Patients with clinical evidence of neurological deficit showed abnormal results (68%) in at least one test of the autonomic nervous system. The sympathetic skin response at the penis was absent in 11 cases (37%) with clinical evidence of neuronal aetiology of the erectile dysfunction and was normal in all cases with positive evidence of a psychiatric origin of erectile dysfunction and no clinical indication of a neuronal deficit. Moreover, the sympathetic skin response at the penis was abnormal in three cases with normal results in the other neurophysiological tests. The results emphasize that the local sympathetic skin response at the penis is a useful extension of autonomic testing in ED patients since this method tests local sympathetic pathways and is sometimes the only evidence for autonomic deficit. From a clinical viewpoint, the sympathetic skin response at the penis is a very simple and time-saving neurophysiological method suitable for clinical routine and also for the investigation of outpatients.

Activation/deactivation of renal Na+,K(+)-ATPase: a final common pathway for regulation of natriuresis.

Renal sodium metabolism, a major determinant of blood pressure, is regulated with great precision by a variety of endocrine, autocrine, and neuronal factors. Although these factors are known to regulate sodium metabolism by affecting the rate of tubular sodium reabsorption, the molecular mechanisms by which they act are poorly understood. Na+,K(+)-ATPase plays a pivotal role for sodium reabsorption in all tubular segments. The activity of this enzyme can be dynamically regulated by phosphorylation and dephosphorylation. Here we summarize both old and new evidence that several major substances believed to be involved in the regulation of sodium metabolism and blood pressure, i.e., the antidiuretic agents angiotensin II and norepinephrine, and the diuretic agents dopamine and atrial natriuretic peptide (ANP), may achieve their effects through a common pathway that involves reversible activation/deactivation of renal tubular Na+,K(+)-ATPase. Regulation of Na+,K(+)-ATPase activity was studied using a preparation of single proximal tubule (PT) segments, dissected from rat kidneys. Na+,K(+)-ATPase activity was stimulated by angiotensin II and the alpha-adrenergic agonist, oxymetazoline, at physiological, nonsaturating Na+ concentrations. These stimulatory effects were blocked by dopamine and ANP as well as by their respective second messengers, cAMP and cGMP. They were also blocked by the specific protein phosphatase 2B inhibitor FK506. These results indicate that regulation of sodium excretion by norepinephrine, angiotensin II, dopamine, and ANP can be accounted for by a bidirectionally regulated intracellular protein phosphorylation cascade that modulates the activity of renal tubular Na+,K(+)-ATPase.

Increased renal tubular Na-K-ATPase activity in Milan hypertensive rats in the prehypertensive period.

Milan hypertensive (MSH) rats develop hypertension around the 3rd-4th week of life and exhibit increased Na-pump activity in adulthood. The present study was performed to evaluate whether or not hypertension is preceded by an increase in Na-K-ATPase activity. Total and ouabain-sensitive ATPase activities were studied in single microdissected medullary thick ascending limb of Henle (mTAL) tubules from MHS, Milan normotensive (MNS) and Sprague-Dawley (SD) rats at 22-24, 26-28 and 45-60 days of age. Data are given as mean +/- SEM. Total and Na-K-ATPase activity exhibited a developmental pattern in MHS, MNS and SD rats. At 22-24 days no difference was seen between MHS and MNS animals. At 26-28 days MHS had a higher total and Na-K-ATPase activity than MNS (3031 + 171 vs 2471 + 178 pmol phosphate/mm tubule per hour, P less than 0.05; 2289 + 205 vs 1653 + 151, n = 10, P less than 0.05). At this age there was still no difference in mean arterial blood pressure (88 + 4 vs 86 + 3 mm Hg, n = 15). Adult MHS rats had higher blood pressure (140 + 9 vs 112 + 8 mm Hg, P less than 0.001) and higher total (3544 + 136 vs 2718 + 215 pmol phosphate/mm tubule per hour, n = 10, P less than 0.01) and Na-K-ATPase activity (2670 + 99 vs 1942 + 217 pmol phosphate/mm tubule per hour, n = 10, P less than 0.05) than adult MNS rats.(ABSTRACT TRUNCATED AT 250 WORDS)