Transrectal US as an adjunct in the diagnosis of rectal and extrarectal tumors

Transrectal ultrasound (US; also called endosonography) was used to evaluate known or suspected rectal and perirectal masses. Thirty-one patients were examined with commercially available endosonographic probes. Those who obtained and interpreted the sonograms had no knowledge of other diagnostic studies, which included digital rectal and sigmoidoscopic examinations, conventional US, and computed tomography (CT). All but one patient underwent surgical exploration for diagnoses that included rectal cancers, perirectal abscesses, presacral endometriosis, intramural dermoid of the rectum, and intramural venous angioma. Transrectal US was able to image all masses situated within 12 cm of the anus. Malignant infiltration of perirectal fat and perirectal node involvement were detected at least as accurately with US as with CT, suggesting that this technique is a cost-effective, reliable adjunct for staging rectal cancers.     

Medical treatment of gastroesophageal reflux disease does not prevent the development of Barrett's metaplasia and poor esophageal body motility

Objective: Duodenal contents refluxing into the esophagus may be involved in the pathophysiology of gastroesophageal reflux disease (GERD). This study was performed to investigate whether medical treatment of GERD aimed at suppression of gastric acid production can prevent the development of complications, such as Barrett's metaplasia or poor esophageal body motility.Design: Retrospective study.Setting: University hospital.Patients: 138 GERD patients were analyzed regarding the development of Barrett's metaplasia or poor esophageal body motility, despite intermittent or continuous treatment with H₂ blockers or omeprazole.Main outcome measures: The rate of patients with Barrett's metaplasia or poor esophageal body motility with or without effective medical treatment.Results: Barrett's metaplasia was found in 33.8% of patients receiving medical treatment, although it was not present when treatment was induced. This rate was 21.9% among patients who were not receiving therapy (not significant). In all, 41.9% of patients with medication had impaired esophageal body motility compared with 59.3% of patients not receiving treatment (P<0.05), but these patients had a significantly shorter history of GERD.Conclusions: Medical treatment with H₂ blockers or omeprazole does not prevent the development of Barrett's metaplasia or poor esophageal body motility.     

Characterization of the clinical effects after the first dose of bacterially synthesized recombinant human granulocyte-macrophage colony- stimulating factor

Bacterially synthesized recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF) is an agent with therapeutic potential for neutropenic states, but even at doses below the maximal tolerated dose adverse effects occur during short courses of administration. We have recognized a syndrome of hypoxia and hypotension that follows the first but not subsequent doses of rhGM-CSF. Thirteen of 42 patients receiving rhGM-CSF in phase I studies and 4 of 6 patients in a phase II study developed a reaction that occurred after the first dose of 24 of 78 cycles of rhGM-CSF therapy. The reaction was characterized by flushing (16 of 24), tachycardia (16 of 24), hypotension (14 of 24), musculoskeletal pain (13 of 24), dyspnea (12 of 24), nausea and vomiting (11 of 24), rigors (5 of 24), involuntary leg spasms (3 of 24), and syncope (3 of 24). The reaction did not occur after any of more than 600 second and subsequent consecutive rhGM-CSF doses. Oxygen saturation decreased during first-dose reactions by 8% +/- 4% as compared with 3% +/- 1% on first days without reactions (P less than .001) and 2% +/- 1% on subsequent days (P less than .001). Pulmonary dysfunction was characterized by hypoxemia (59 +/- 9 mm Hg, mean +/- SD) that was fully correctable with supplementary oxygen, decreased single-breath carbon monoxide diffusion capacity, and increased alveolar-arterial oxygen gradients (25 +/- 6 to 60 +/- 4 mm Hg, mean +/- SD), but no significant abnormalities on chest roentgenogram or lung perfusion scan. Factors predisposing to reactions were rhGM-CSF dose greater than or equal to 3 micrograms/kg (P less than .01), intravenous (IV) rather than subcutaneous (SC) administration (P less than .05), occurrence of a reaction after the first dose of a previous cycle of rhGM-CSF therapy (P less than .01), and for patients receiving 15 micrograms/kg/d by SC bolus, the presence of lung cancer (P less than .05). Administration of 15 micrograms/kg/d rhGM-CSF by 24-hour SC infusion rather than SC bolus resulted in a delayed onset of reaction from 30 +/- 8 minutes to 240 +/- 190 minutes (mean +/- SD, P less than .001), and a slower rate of initial transient decrease in neutrophil levels and a more prolonged duration of transient leukopenia. The time of onset of reactions correlated with the rate of rise of rhGM-CSF levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dermatan sulphate induces plasminogen activator release in the perfused rat hindquarters

Heparin or heparin-like substances have been described to induce the release of plasminogen activator (PA) activity in different animal perfusion models. In this paper we report that Dermatan Sulphate (DS) is able to induce PA activity release in the perfused rat hindquarters. Perfusion of different doses of DS (0.1 to 0.8 mg/mL) stimulates a release of PA activity that is maximum after the initial two minutes of perfusion. The amount of PA activity released rises progressively within a certain concentration range of DS (0.1 to 0.4 mg/mL) and declines thereafter (0.6 to 0.8 mg/mL). The type of PA activity increased during DS perfusion was characterized by SDS-PAGE and fibrin autography as tissue-type PA (t-PA) on the basis of its mol wt (67,000 d) and inhibition by a specific anti t-PA antiserum. This effect might be considered as potentially contributing to the antithrombotic activity of DS, at least at the local level.     

An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, beta-globin haplotypes, alpha-globin gene number, gender, and age

Five factors have been shown to influence the 20-fold variation of fetal hemoglobin (Hb F) levels in sickle cell anemia (SS): age, sex, the alpha-globin gene number, beta-globin haplotypes, and an X-linked locus that regulates the production of Hb F-containing erythrocytes (F cells), ie, the F-cell production (FCP) locus. To determine the relative importance of these factors, we studied 257 Jamaican SS subjects from a Cohort group identified by newborn screening and from a Sib Pair study. Linear regression analyses showed that each variable, when analyzed alone, had a significant association with Hb F levels (P < .05). Multiple regression analysis, including all variables, showed that the FCP locus is the strongest predictor, accounting for 40% of Hb F variation. beta-Globin haplotypes, alpha-globin genes, and age accounted for less than 10% of the variation. The association between the beta-globin haplotypes and Hb F levels becomes apparent if the influence of the FCP locus is removed by analyzing only individuals with the same FCP phenotype. Thus, the FCP locus is the most important factor identified to date in determining Hb F levels. The variation within each FCP phenotype is modulated by factors associated with the three common beta-globin haplotypes and other as yet unidentified factor(s).