Identification of a novel HLA-DRB1*13 variant allele: DRB1*13:154.

A newly identified allele, named HLA-DRB1*13:154, differs from DRB1*13:13 by the single nucleotide substitution 227T-A at codon 47 in exon 2.

Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Renal safety of tenofovir in HIV-infected children: a prospective, 96-week longitudinal study.

BACKGROUND: The renal safety of tenofovir in HIV-infected children has not been well studied. In paediatrics, prediction of glomerular filtration rate (GFR) is usually obtained by the Schwartz equation; the Cockcroft-Gault equation is considered more appropriate in children aged >12 years, but can be misleading in younger children. The aims of this study were to assess renal safety and GFR changes as estimated by the Schwartz and Cockcroft-Gault equations in HIV-infected children treated with tenofovir for 96 weeks. METHODS: Several parameters of glomerular and tubular function were prospectively assessed (at baseline and at weeks 24, 48, 72 and 96) in 27 HIV-infected children (aged 4.9-18.0 years) receiving a tenofovir-containing antiretroviral regimen. GFR was estimated using Schwartz and Cockcroft-Gault equations in children younger and older than 12 years, respectively. RESULTS: No child experienced a grade 1 (> or =44 micromol/L) or higher increase in serum creatinine or a grade 1 (< or =0.71 mmol/L) or higher hypophosphataemia. Serum bicarbonate values were in the normal range for age at baseline. Mean serum creatinine, serum phosphorus and serum bicarbonate values remained unchanged. No child showed proteinuria, microalbuminuria or glycosuria at baseline or during the study period. The mean urinary protein/creatinine, albumin/creatinine, alpha(1)-microglobulin/creatinine and maximal tubular phosphate reabsorption (TmPO(4)/GFR) ratios remained unchanged. Up to week 96, no patient experienced a significant decrease in GFR, as estimated by the more appropriate formula for age. CONCLUSION: Through 96 weeks, we found no evidence of impaired glomerular or tubular renal function in tenofovir-treated HIV-infected children.

[Acid-base equilibrium in the critically ill]. / L'equilibrio acido-base nel paziente in area critica.

The reasons causing a patient to be hospitalized in the ICU, the degree of organs involvement and the subsequent therapeutic interventions, are all elements that can interfere with the acid-base homeostasis. It may be difficult to correctly evaluate the disturbances of the acid-base balance and to understand the underlying physiopathological process. Though, it is crucial to clarify the steps that resulted in the alteration, in order to increase the probability of detecting the correct diagnosis and therapy. Two other elements make the understanding more complex first, it is difficult to estimate, even approximately, the degree of involvement of the 'structural' buffer systems (intracellular buffers, proteins, activation or inhibition of metabolic pathways, etc.) to calculate the total acid load and then quantify the bases necessary to restore the patient balance. Then, the disorder severity is too often assessed through the arterial blood gas analysis parameters, which limits observation to a restricted vascular area, and the disorder assessment to the bicarbonate-carbonic acid system.

Characterization of a novel HLA-B*18 variant allele, HLA-B*18:122, by genome sequencing.

The HLA-B*18:122 allele showed four nucleotide differences from HLA-B*18:01:01:01.

Identification of a new HLA-A*24 allele, A*24:309, in an Italian bone marrow donor.

A novel class I human leukocyte antigen allele HLA-A*24:309 is described.

Reduced intracellular pH in lymphocytes from the spontaneously hypertensive rat.

This study was designed to determine the cytoplasmic pH (pHi) profile of lymphocytes from a rat model of genetic hypertension that is well suited for study before and after the development of spontaneous hypertension. For this purpose, pHi was measured in thymic lymphocytes obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto (WKY) control rats using 2',7'-bis carboxyethyl-5,6-carboxyfluorescein (BCECF), a pH-sensitive fluorescence probe. At the age of 16-20 weeks, pHi of lymphocytes suspended in a HCO3-free HEPES-buffered solution, was markedly lower in the SHR than in the WKY rats (7.07 +/- 0.02, n = 16 and 7.22 +/- 0.01, n = 15, respectively, p less than 0.001), whereas systolic blood pressure was higher in SHR than in WKY rats (175 +/- 5.0 and 105 +/- 3.0 mm Hg, respectively, p less than 0.001). In rats less than 5 weeks of age, pHi was also lower in SHR than in WKY rat lymphocytes (7.12 +/- 0.04, n = 11 and 7.23 +/- 0.04, n = 11, respectively, p less than 0.05), although at this age systolic blood pressure was not different between the two groups (87 +/- 4.0 and 85 +/- 3.0 mm Hg, respectively). In lymphocytes suspended in a more physiological HCO3/CO2-buffered solution, pHi was again lower in the adult SHR than in the WKY rat (7.18 +/- 0.02, n = 16 and 7.31 +/- 0.02, n = 16, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Association of apolipoprotein E polymorphism to clinical heterogeneity of multiple sclerosis.

In this study we investigated the distribution of apolipoprotein E (APO E) genotypes in sporadic multiple sclerosis (MS) cases and in normal controls. Later onset of chronic progressive MS was observed in patients carrying the epsilon2 allele, whereas APO E alleles were found at similar frequency in MS and in the control population. These findings indicate that clinical heterogeneity, but probably not susceptibility to the disease, is associated to APO E genotypes.

Shared-epitope HLA-DRB1 alleles and sex ratio in Italian patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association between the HLA-DRB1 alleles sharing the epitope (Q/R)(K/R)RAA and rheumatoid arthritis (RA) in a large sample of Italian patients (N = 264) recruited from a single centre over the last 5 years. METHODS: Patients' classification according to the ACR criteria. DNA typing of HLA-DRB1 alleles by conventional polymerase chain reaction sequence specific oligonucleotide probing techniques. RESULTS: Low-resolution DRB1 "generic" typing showed a significantly higher frequency of DR4+ RA patients as compared to normal controls. Both DR1 and DR10 specificities were over-represented in our patients, but neither reached the statistically significant P level of 0.05 after Bonferroni's correction. However, direct search of Q(K/R)RAA epitopes, which are present in most DR4+ and DRl+ samples, demonstrated that these motifs were found at increased frequencies in RA patients. Stratification according to gender did not show differences in the proportion of disease-associated HLA alleles. CONCLUSIONS: Our study confirms the association of HLA-DR4, and -DR1 alleles, and more generally speaking of the shared epitopes Q(K/R)RAA, with disease susceptibility in Italian patients.

Aneurysm of the celiac trunk: diagnosis with US-color-Doppler. Presentation of a new case and review of the literature.

Aneurysms of the celiac trunk are the rarest forms of aneurysms of the visceral arteries. Since 1958, when Schumaker reported the first case to be successfully treated surgically, only 69 cases have been reported in the international literature. The detection of such aneurysms, which are often asymptomatic, is mostly occasional. Approximately 15-20% of cases may be complicated by rupture with a mortality rate of around 80%. This eventuality makes surgical treatment mandatory even in asymptomatic cases. The authors report on their experience with the surgical treatment of one case of aneurysm of the celiac trunk and then go on to review the relevant literature.

[Aneurysm of the celiac trunk. Presentation of a clinical case and review of the literature]. / Aneurisma del tripode celiaco. Presentazione di un caso clinico e revisione della letteratura.

The aneurysms of the celiac trunk are the rarest aneurysms of the visceral arteries. From 1958 only 69 cases have been reported in the international literature. They are frequently asymptomatic and their discovery is more often occasional. They can rupture in 15-20% of the cases with a mortality approaching 80% of the cases. This explains the need of a surgical treatment even in the asymptomatic cases. Personal experience in the surgical treatment of a case of aneurysm of the celiac trunk is reported and a survey of the literature on this matter is made.

[Presence of HLA-DRB1 alleles in a group of patients with rheumatoid arthritis treated with low doses of sodium aurothiomalate]. / Presenza degli alleli HLA DRB1 in un gruppo di pazienti con artrite reumatoide trattato con basse dosi di aurotiomalato di sodio.

The good results of a therapy with small doses of sodium aurothiomalate (20 mg/month) in 17 patients suffering from rheumatoid arthritis are reported. The mean age +/- ESM at the beginning of treatment was 59.9 +/- 3.2 years, the mean duration of disease was 1.3 +/- 0.5 years. The lowest grade of disease activity (1) according to Mallya and Mace's (1981) criteria was observed in 12 patients (70%) after a period of 1.7 +/- 0.6 years (mean +/- ESM). This grade of activity persisted in 11 patients and remained for 3 years in 1 patient. In the other 5 patients a low or middle activity of disease persisted. The relationship between therapeutic results and HLA DRB1 prevalence was investigated. The LLEQRRAA and LLEQKRAA sequences are present in 3 patients, i.e. 17.9%. This frequency is not significantly different from the frequency (28.6%) observed in a control group of healthy subjects. Therefore these sequences, at least in Italian people, cannot be considered a factor of susceptibility to RA. They may be a factor of evolution to a more severe disease. Dermatological side effects were evident only in 2 patients; one of these patients was HLA DR5 positive. The results observed in DR7 positive patients were not different from the results observed in the other patients; therefore, DR7 positive patients could responders to gold treatment, even with low doses.

[Chronic rupture of abdominal aortic aneurysms. (Report of 3 cases)]. / Rottura cronica degli aneurismi dell'aorta addominale. (Su tre casi osservati).

Rupture of an abdominal aortic aneurysm often presents with an abdominal pain, hypotension and a pulsatile abdominal mass. In the last years same clinical reports describe patients with less apparent clinical signs who were found later in their evaluation to have a contained rupture of an abdominal aortic aneurysm. The diagnosis may be delayed by consideration of other disease causing similar symptoms (herniated disc, renal colic). In these patients with confusing abdominal symptoms CT scan provides a rapid and noninvasive diagnosis. We report three cases of contained rupture of an abdominal aortic aneurysm evaluated by computed tomography with different clinical presentation: back pain for erosion into the lumbar vertebral bodies, lower extremity neuropathy and obstructive jaundice. All patients were operated on within 24 hours on admission; there was no operative mortality and survival was 100% at one year.

Intracellular H+ buffering power and its dependency on intracellular pH.

Intracellular hydrogen ion (H+) buffering power, conventionally defined as the amount of acid or base that would have to be introduced into the cell cytosol to decrease or increase ipH by one pH unit, is generally said to increase as intracellular pH (ipH) decreases. This implies that the cell has a lesser capability to resist acute acid or base perturbations at its steady state ipH than at any lower ipH. We re-examined this notion, reasoning that the logarithmic nature of the pH unit could limit the validity of the conventional expression of buffering power in imparting physiologic insight into the mechanisms of cellular H+ homeostasis. The mathematical derivation of the formula, delta i[NH4+]/delta ipH, conventionally used to estimate buffering power using the NH4Cl technique, revealed that this parameter is, by design, inversely proportional to the exponential of ipH. This a priori dependence on pH dictates an increase in buffering power with decreasing ipH, and thereby interferes with the assessment of the physiologic capability of the intracellular milieu to buffer protons at different ipH levels. To circumvent this problem, buffering power was defined as the amount of hydrogen ions that would have to be added to or removed from the cell to effect a change in the concentration of H+ in the cell cytosol of 1 mM (a term heretofore referred to as the cell H+ buffering coefficient). The mathematical derivation of the formula used to calculate the cell H+ buffering coefficient, delta i[NH4+]/delta[H+]i, does not suffer from an a priori dependence on ipH.(ABSTRACT TRUNCATED AT 250 WORDS)