Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Low acid output in Pima Indians

Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indian and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of an acaloric liqid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and aslow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased pervalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.Supported in part by research Contract 1-Am-6-2219 and grant AM 13233 from the National Institutes of Health, Bethesda, Maryland     

Inhibitory effect of intragastric glucose on gastric acid secretion and gastric emptying of liquids in man

Intragastric glucose inhibits gastric acid secretion and gastric emptying in man. To determine if these effects are mediated by somatostatin—a known inhibitor of gastric acid production, gastrin secretion, and gastric motility—the plasma somatostatin-like immunoreactivity (SLI) levels were determined in healthy human subjects after an intragastric load of 30% glucose solution. These findings were compared with results after an instillation of distilled water. Following the glucose load, the intragastric acid concentration, the acid output, and the fractional gastric emptying rate declined significantly (P<0.01) before either the plasma glucose or plasma insulin levels had increased. Neither the gastrin nor SLI plasma concentrations changed after the water or glucose load. These findings suggest that the suppression of gastric acid secretion and inhibition of the rate of gastric emptying that occur with intragastric glucose are mediated by factors other than changes in the peripheral circulating levels of SLI, gastrin, insulin, or glucose.     

Quality of life in aortic valve replacement: pulmonary autografts versus mechanical prostheses

OBJECTIVES: We sought to determine whether the quality of life (QoL) is different in patients after aortic valve replacement with mechanical prostheses or pulmonary autografts. BACKGROUND: Quality of life after mechanical valve replacement may be affected by the risk of thromboembolism and anticoagulation, and after autograft implantation, by the risk of degeneration and re-operation especially of the homograft. METHODS: Two groups of 40 patients each--one after the autograft procedure (group I) and one after mechanical valve implantation (group II)--were matched for age, gender and length of follow-up. At latest follow-up, all patients underwent routine echocardiography, the short-form health survey (SF-36) QoL survey and an extensive psychological investigation. RESULTS: Patients with an autograft showed better QoL scales, as compared with mechanical valve recipients. The difference was significant for both the physical (72.72+/-20.00 vs. 60.27+/-26.07, p = 0.021) and psychological health sum scores (74.71+/-21.03 vs. 64.71+/-23.49, p = 0.046) and for the subtests of physical functioning (73.72+/-22.44 vs. 62.77+/-25.42, p = 0.049), physical pain (88.39+/-19.13 vs. 73.36+/-27.08, p < or = 0.006), general health perception (64.37+/-17.88 vs. 51.86+/-22.86, p < or = 0.008) and health change (61.89+/-18.94 vs. 50.11+/-24.37, p = 0.02). The QoL variables did not correlate to pressure gradients, ejection fraction and New York Heart Association functional class. Psychometric tests revealed no meaningful differences between the groups. CONCLUSIONS: This study provides some evidence that patients with pulmonary autografts have greater benefit in terms of QoL, as compared with recipients of mechanical valve substitutes.     

Artificial intelligence in gastroenterology: A state-of-the-art review

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.     

Cardiac rhythm and conduction after two-stage anatomic correction of simple transposition of the great arteries

To assess postoperative arrhythmias and AV-conduction defects associated with anatomic correction of simple transposition of the great arteries, 207 standard 12-lead surface and 43 24-hour electrocardiograms of all 17 patients followed after anatomic correction for up to 6.5 years were reviewed. No dysrhythmias or AV-conduction delays definitely attributable to anatomic correction were observed. One patient with a severe complex supraventricular tachyarrhythmia after a Blalock-Hanlon procedure has improved markedly, exhibiting respiratory AV-dissociation and 5 premature atrial complexes/minute 5 years after anatomic correction.     

Replacement of the aortic root by free implantation of a stentless aortic porcine bioprosthesis in a patient with aneurysm of the sinuses of Valsalva

In a patient with aneurysms of the sinuses of Valsalva a stentless porcine bioprosthesis was implanted with excellent hemodynamic and clinical short-term results. The implantation technique was similar to the technique used for the implantation of a composite graft. The postoperative study revealed a pressure gradient of 7 mmHg between the left ventricle and aorta and no regurgitation. Although the implantation of a porcine aortic root including a part of the ascending aorta without any artificial stenting material is feasible, one should be aware of the specific technical difficulties due to the increased rigidity of the fixated tissue. To our knowledge this is the first report of an implantation of a stentless aortic root porcine bioprosthesis for the treatment of aneurysms of the sinuses of Valsalva.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.