Hypokalemic metabolic alkalosis: apropos of a case of Gitelman's syndrome

We present a case of Gitelman's Syndrome in a 20 year-old woman who came to our service with weakness, asthenia, leg cramps and tetany. Laboratory studies revealed metabolic alkalosis with hypokalemia, hypomagnesemia and low calcium in a 24-hour urine test. The diagnosis of this syndrome is made in some cases during adult life because this syndrome is asymptomatic over several years. Gitelman's Syndrome is autosomal recessive as is Bartter's Syndrome. The gene is located in chromosome 16q, which encodes the cotransporter Na/Cl sensitive to thiazide in the distal convoluted tubule. The defect of cotransporter produces an alteration of sodium reabsorption that causes electrolytic disorders typical of this Syndrome and different from Bartter's Syndrome. The typical electrolytic alterations are hypocalciuria and hypomagnesemia secondary to high urinary magnesium excretion. The prognosis of this syndrome is excellent and treatment consists in correction of serum electrolytes with oral administration of magnesium and potassium. In spite of this treatment, in some cases it is very difficult to reach normal serum levels of magnesium because of the high doses of oral magnesium, which produce common crises of diarrhea that increase magnesium gastrointestinal losses.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

PLP1 gene analysis in 88 patients with leukodystrophy

Pelizaeus–Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty‐eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation‐dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array‐CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array‐CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.     

Dengue nonstructural protein-1 status is not associated to circulating levels of interleukin-17, C-reactive protein and complement in children with acute dengue

BackgroundDuring dengue infection increase in plasma level of various substances have been reported. Some of those molecules are related to the virus biology and others result of the interaction virus–host. Nonstructural protein-1 (NS1) secreted by dengue virus has been reported to have a role in dengue pathogenesis. NS1 is capable of interacting with complement to evade viral clearance. However, there is little information about the presence of serum NS1 and the levels of other molecules related to dengue pathogenesis.ObjectivesThe aim of this study was to determine the association of the NS1 status and the circulating levels of interleukin-17 (IL-17), C-reactive protein (CRP), C3 and C4 in acute dengue.Study designIn this study the serum presence of NS1, IL-17, CRP, C3 and C4 was determined in children with acute dengue. IL-17, CRP, anti dengue-IgG content was measured by ELISA, C3 and C4 levels by an immunoturbidimetric assay and NS1 by an immunochromatographic assay.ResultsAll patients were positive for dengue infection as shown by antibodies anti-dengue and/or virus isolation. Increased levels of IL-17, CRP and C4 no related to the presence of NS1 were found in the patients. Values of C3 remained similar to controls.ConclusionsThese findings suggest that NS1 does not module the production of studied molecules during dengue infection.     

Long interval between HCV infection and development of hepatocellular carcinoma

Abstract: A high prevalence of HCV infection has been reported in patients with hepatocellular carcinoma. The progression from acute transfusion-associated hepatitis to hepatic cirrhosis and hepatocellular carcinoma has been suggested in several studies to be very long. We have investigated the prevalence of anti-HCV and the interval between HCV infection and hepatocellular carcinoma among 191 consecutive patients with cirrhosis and liver-cell carcinoma. Serum samples from 191 patients with cirrhosis and hepatocellular carcinoma, consecutively diagnosed in our hospital between 1988 and 1993, were tested for serological markers of HBV and HCV infection. One hundred and forty-eight patients (77.5%; 95% confidence interval (c.i): 76% to 80%) were anti-HCV positive by 2nd generation enzyme immunoassay (confirmed by 2nd generation recombinant immunoblot assay) and 152 patients (79.5%; 95% c.i: 76% to 80%) were anti-HCV positive by 3rd generation enzyme immunoassay, while only 14 (7.4%; 95% c.i: 5% to 10%) were HBsAg positive. Of the 29 anti-HCV positive patients with previous transfusion, the interval between the date of blood transfusion and the diagnosis of hepatic cirrhosis was 24±12.5 years and that of hepatocellular carcinoma was 26.8±12.4 years. These results confirm the high prevalence of HCV infection in patients with hepatocellular carcinoma and the slow sequential progression from HCV infection through cirrhosis and hepatocellular carcinoma.