Eighteen month follow up of Helicobacter pylori positive children treated with amoxycillin and tinidazole.

Sixty three children with dyspepsia (mean age 12 years, range one to 18, M/F 41/22) were Helicobacter pylori positive by histology of gastric antral biopsy specimens and were treated with a six week course of amoxycillin (50 mg/kg) and tinidazole (20 mg/kg). The endoscopic diagnoses were: normal (16), nodular gastritis (19), oesophagitis (four), duodenal ulcer (13), and gastric ulcer (11). H pylori was eradicated in 54 (87%) and histological gastritis resolved in 51 and was improved in the other three. Repeat investigation was offered at six monthly intervals. Reinfection was found in three of 34 (9%) at six months, in none of 22 at 12 months, and in two of 18 (11%) at 18 months, yielding an 18 month cumulative relapse rate of 20%. Children with persisting infection despite treatment remained positive during follow up. Serum H pylori IgG concentrations fell after treatment (p < 0.001), and for individual children during follow up there was a progressive decline, but an increased concentration indicated recurrence. After eradication of H pylori by combined amoxycillin and tinidazole treatment, only a minority of children relapse during the ensuing 18 months.     

Role of arginine residues in the coagulant activity of high molecular weight kininogen

High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.     

Influence of sex and age on blood pressure variability

The aim of this study has been to identify changes of 24-h blood pressure variability, as related to age and sex in hypertensive subjects. As regards this point several international studies have shown the increase of morbidity and mortality caused by cardiovascular diseases in postmenopausal women produced by a lack of sex hormones, which had protected the women until this period. Each hypertensive subject was submitted to an ambulatory blood pressure monitoring (ABPM) and two variability indexes were obtained: S.D. and coefficient of variation (CV). The results have shown a strict correlation between blood pressure variability and age, without significant sex-related differences. A decrease of blood pressure variability and mean blood pressure (BP) values have also been found, in the night-time with respect to the day-time data; it was more pronounced in females than in males but this would not seem an age-related difference. Despite the fact that the correlation between blood pressure variability and age is very significant in every considered period in males, it has been found that women have statistical differences only in the day-time and in the nocturnal diastolic blood pressure (DBP) fluctuations. This might be caused by other independent factors, such as a postmenopausal lack of sex hormones.     

Effect of surfaces on fluid-phase prekallikrein activation

The activation of prekallikrein by factor XII fragments (XIIf), during incubation in plastic tubes was previously noted to be increased by high molecular weight (HMW) kininogen as well as other plasma proteins. In this report, we investigated the mechanism responsible for this increase. Although we confirmed that HMW kininogen, bovine serum albumin, fibrinogen, cold insoluble globulin, and mixed phospholipids apparently increased prekallikrein activation, we found that the product of prekallikrein activation (kallikrein) lost substantial activity in less than 0.5 min after exposure to a variety of fresh surfaces. This loss was partially prevented by the presence of various proteins and phospholipids. Similar protection against inactivation of XIIf, the enzyme in this reaction, was also found. In contrast, no loss of the substrate, prekallikrein, was observed during incubation. The loss of kallikrein activity was found to be proportional to the surface area of the incubation vessel as well as the concentration of kallikrein. Further loss of kallikrein activity could also be prevented by pretreating the vessel with kallikrein. We therefore conclude that various substances apparently affect prekallikrein activation in a purified system by preventing the enzyme and product in the reaction mixture from losing activity due to adsorption to a surface.     

Species-dependent variations in erythrocyte membrane skeletal proteins

Two mammalian species (porcine and murine) have erythrocytes that are being widely used to study membrane protein synthesis and red cell aging. Erythrocytes of these species however, are significantly smaller than those of the human. Before results obtained from study of these red cells can be applied to human cells, the membrane skeleton of these species must be investigated to determine if the skeletal elements are equivalent. Both pig and mouse bands 4.1b were of lower molecular weight than human 4.1b, and the a/b ratio was lower. In each species, 4.1a and b were sequence-related phosphoproteins, and yielded substantially different one-dimensional peptide maps. Band 3 of pig and mouse erythrocytes had a higher molecular weight than human band 3 and also had differing one-dimensional peptide maps after limited proteolytic cleavage with three different enzymes. In each species, free band 3 and band 3 bound to the membrane skeleton had identical peptide maps. Other major membrane skeletal components (spectrin, actin, and bands 2.1 and 4.2) seem to be very similar in molecular weight in various species. These results demonstrate that the molecular weights and relative proportions of the membrane skeletal elements are species dependent.     

Treatment of childhood peptic oesophagitis with famotidine or alginate-antacid

Both antacids and H2 receptor antagonists have a potential role in treating peptic oesophagitis associated with acid reflux. The aim of this study is to assess the efficacy and tolerability of famotidine and alginate-antacid in children with endoscopically documented peptic oesophagitis. We compared clinical, endoscopic and histological response to alginate-antacid (1 tablet to be chewed 30 min after each meal and at bed time) or famotidine (1 mg/kg before supper at 7 pm) in 49 children (mean age 9 years, 34 males). Twenty-four of them were randomly allocated to alginate-antacid treatment (group A), twenty-five to famotidine (group B). Both treatments were protracted for six months and endoscopy was then repeated. Symptoms disappeared in 43.4% and improved in 47.8% of children of group A and disappeared in 91.6% of those of group B (p less than .05). Mean time for symptom disappearance was 17 weeks for group A and 5 weeks for group B (p less than .01). After six months, at endoscopy oesophagitis was healed in 43.4% in group A and in 41.6% of group B, the difference between the two groups was not significant, however the improvement of endoscopic grades induced by famotidine was significantly better (p less than .05). Histology showed a healed peptic oesophagitis in 52.2% of the children in group A and in 70.8% of group B (p less than .001). No toxicity was observed with either treatment. We conclude that famotidine is superior to alginate-antacid in treating peptic oesophagitis associated with acid reflux, since it induces a better symptomatic response and a greater improvement of endoscopic lesions.     

Factors influencing the acceleration of human factor XIa inactivation by antithrombin III

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.     

Helicobacter pylori in children with peptic ulcer and their families

Little is known about the source and spread of Helicobacter pylori, but transmission from infected family contacts has been suggested. We have therefore investigated 15 children with peptic ulcer and their first-degree relatives for H. pylori. Serum anti-H. pylori IgG, pepsinogen I, and gastrin levels were measured. Endoscopy was carried out on the children and relatives, and biopsies were taken from the gastric antrum for histology, microbiology, and urease testing. Six of 11 children with duodenal ulcer (55%) and two of four children with gastric ulcer (50%) were positive for H. pylori. Fourteen of 16 parents (87%) and eight of 13 siblings (61%) of H. pylori-positive children with peptic ulcer were also infected compared with eight of 14 parents (57%) and none of four siblings of H. pylori-negative children with peptic ulcer (P less than 0.10, greater than 0.05, and NS, respectively). The children with H. pylori-negative peptic ulcer and negative siblings combined were younger than positive children with peptic ulcer and positive siblings (P less than 0.001). The reliability of serum anti-H. pylori IgG level as a screening test for infection was confirmed. These findings call into question a pathogenetic role for H. pylori in some childhood peptic ulceration, but do suggest that person-to-person spread of infection occurs.