Endoscopic evaluation of 125 cases of upper gastrointestinal bleeding.

The fiberoptic panendoscope has been shown to be superior to the UGI series in diagnosing the site(s) of upper gastrointestinal bleeding (UGIB). Recent data has shown that gastritis has replaced peptic ulcer disease (PUD) as the leading cause of UGIB since the diagnosis can now be made with the endoscope. Our clinical experience differs from this. One hundred twenty five cases of UGIB from December 1975 to December 1978 were reviewed. The patients ranged in age from 11 to 91 years. There were 83 males and 42 females included in the study. Twenty-four per cent of the patients were actively bleeding at the time of endoscopic examination, and 62% received two or more units of blood. Endoscopic examination was technically successful in all patients, and there were no deaths or complications. One hundred twenty three lesions were found in 117 patients for a diagnostic accuracy of 93.9%. In eight patients, no bleeding site was found, resulting in a failure rate of 6.1%. PUD accounted for 74.9% of the bleeding sites, while gastritis accounted for only 0.8%. Mallory-Weiss tears of the esophagus accounted for 9.8% and esophageal varices for 4.9%. Thirty-five per cent of the patients had associated lesions, with gastritis and esophagitis being the most common. Eighteen patients (14.4%) required surgical intervention. Seventeen patients had PUD. There was one death, for a mortality rate of 5.5%. The medical mortality rate was 0.9%. The benefits of endoscopy in UGIB are still controversial. An important subgroup of patients with the "visible vessel" in the ulcer bed has been identified recently by others. If not bleeding at the time of endoscopy, 70% will rebleed. It is our opinion that it is important to identify this patient, as well as to know if one is treating gastritis, PUD, or varices. Finally, electrocoagulation of bleeding points, as well as the development of the laser and application of adhesives or clotting agents through the endoscope, will change the management of UGIB.     

Effects of hydration and dehydration on body composition analysis: a comparative study of bioelectric impedance analysis and hydrodensitometry.

Since 1983, bioelectric impedance has been researched with respect to its validity and reliability in the determination of body composition. It continues to be compared to hydrostatic weighing, the anthropometric "gold standard". This study was designed to investigate the relationship between bioelectric impedance analysis (BIA) and hydrodensitometry (HW) under three conditions: control, hydration and dehydration. Caucasian males (aged 18-44 years) served as subjects (n = 10). Body composition was determined by BIA and HW before intervention, 30 minutes post-hydration, and following a combination of exercise and sitting in a steam room to decrease body weight by two to four percent (mean = 2.81%). Statistical treatment by two-way analysis of variance for repeated measures revealed that although there were no significant differences between the two techniques of body composition determination under any of the three conditions, there was a statistically significant decrease in percent body fat determined in the dehydrated state as compared to the control and hydrated conditions. Recommendations include the determination of hydration state prior to engaging in body composition analysis by either method.     

Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer

Ultraviolet (UV) light has been associated with the development of human non-melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53 tumour suppressor gene. In order to determine the UV-induced p53 mutation spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was UV-irradiated in vitro and transfected into a yeast strain that contained the ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones contained 51 mutations. Seven mutations were tandem base pair substitutions, four of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent (41/51) of the mutations were single or non-tandem base pair substitutions, the majority of which (27/41) were C-->T transitions. Ninety-five percent of such mutations occurred at dipyrimidine sites. Through a rigorous statistical test, the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008) from the one induced by the antineoplastic drug chloroethyl-cyclohexyl-nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4). These results demonstrate that the assay allows the determination of carcinogen-specific p53 mutation fingerprints and represents a new tool for molecular epidemiology.      

Premedical anatomy experience and student performance in medical gross anatomy

Gross anatomy is considered one of the most important basic science courses in medical education, yet few medical schools require its completion prior to matriculation. The effect of taking anatomy courses before entering medical school on performance in medical gross anatomy has been previously studied with inconsistent results. The effect of premedical anatomy coursework on performance in medical gross anatomy, overall medical school grade point average (GPA), and Comprehensive Osteopathic Medical Licensing Examination Level 1 (COMLEX 1) score was evaluated in 456 first‐year osteopathic medical students along with a survey on its perceived benefits on success in medical gross anatomy course. No significant differences were found in gross anatomy grade, GPA, or COMLEX 1 score between students with premedical anatomy coursework and those without. However, significant differences and higher scores were observed in students who had taken three or more undergraduate anatomy courses including at least one with cadaveric laboratory. There was significantly lower perceived benefit for academic success in the medical gross anatomy course (P<.001) from those students who had taken premedical anatomy courses (5.9 of 10) compared with those who had not (8.2 of 10). Results suggest that requiring any anatomy course as a prerequisite for medical school would not have significant effect on student performance in the medical gross anatomy course. However, requiring more specific anatomy coursework including taking three or more undergraduate anatomy courses, one with cadaveric laboratory component, may result in higher medical gross anatomy grades, medical school GPA, and COMLEX 1 scores. Clin. Anat. 30:303–311, 2017. © 2017 Wiley Periodicals, Inc.     

Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine

Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine.     

Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane

Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane.