Exercise electrocardiogram testing and imaging in women

The increased awareness of the incidence and risk of coronary heart disease (CHD) has increased the efforts of physicians to identify women with CHD as early as possible. Exercise electrocardiogram (ECG) testing and imaging have been used in this manner for men and women but represent unique challenges with regard to women. Exercise ECG testing, which determines the presence of coronary artery disease by the provocation of ST depression and chest pain, has a lower positive predictive value in women than in men of the same age. This is explained by a lower prevalence of CHD in female patients with symptoms and (to a lesser extent) by the reported lower sensitivity and specificity of the test in women as compared with men. Exercise nuclear isotope myocardial perfusion imaging and exercise echocardiography have higher reported specificity and sensitivity, and new imaging agents, contrast echo agents, and acquisition protocols have reduced the limitations of these studies in selected women. The value of the exercise ECG examination with regard to CHD event risk assessment is equal in men and women and should be incorporated into the clinical evaluation of appropriate women patients.     

Enhancement of in vivo and in vitro immune functions by a conformationally biased,response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design

A conformationally biased, agonist of human C5a_65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88^−/−). Serum from mice immunized with EP67–ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88^−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.     

Fetal pancreas transplantation in miniature swine. IV. Suppression of DTH and MLR responses by treatment with ultraviolet light-irradiated peripheral blood lymphocytes

Irradiation of peripheral blood lymphocytes of miniature swine with ultraviolet light prevented them from initiating proliferative responses in allogeneic mixed lymphocyte reactions and also reduced IL-2 production in these MLRs. When pigs were injected in a series of 4-5 weekly transfusions with UV-irradiated allogeneic PBL differing at the MHC, PBL of recipient pigs progressively responded less strongly to donor PBL in MLRs over the treatment period. These pigs also gave negligible delayed-type hypersensitivity responses to donor PBL at the end of the treatment period. Of the seven UV-irradiated PBL-treated pigs, four produced no antidonor PBL antibody and three produced antibody. Serum from the three antibody-producing pigs also suppressed MLRs of unrelated PBL. By contrast, pigs that received a series of injections of untreated allogeneic PBL gave strong DTH responses to donor PBL and heightened proliferation in MLRs with donor PBL, and all produced antidonor PBL antibody.     

Circadian esophageal motor function in patients with gastroesophageal reflux disease

Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated.     

Effect of propranolol on nitrogen and energy metabolism in sepsis

Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.     

Trans-catheter closure of patent ductus arteriosus in childhood--an alternative to surgical ligature]

Transcatheter closure of a persistently patent ductus arteriosus (PDA) was successfully performed in four children using a Rashkind double disk umbrella device. Mean age was 5.1 +/- 1.5 (2.8 to 6.3 years) and weight 18.8 +/- 3.8 kg (14.1 to 22.3 kg). In all children the PDA was the only cardiac lesion and was diagnosed clinically and by means of continuous wave and color-coded doppler echocardiography. After angiographic measurement of PDA size the correlating device was implanted. The ductus was closed immediately in two children, whereas there was a residual angiographic shunt in the others. Echocardiography performed within 24 hours showed a minimal shunt only in one of these cases. The shunt had disappeared at the one month follow up study. We experienced none of the reported possible complications. Transcatheter closure of the PDA after the neonatal period seems to be a safe and effective alternative to surgical ligation as our early experience shows, and should become the procedure of first choice in these patients.     

Lack of effect of paracetamol on the pharmacokinetics of chloramphenicol.

The effect of oral paracetamol (1 g) on the pharmacokinetics of oral chloramphenicol (500 mg) was examined in five adult male Zimbabwean patients with normal hepatic and renal function. No significant alteration of half-life, area under the concentration-time curve or peak concentration of chloramphenicol was observed. The previously reported, potentially serious interaction between chloramphenicol and paracetamol administered intravenously was not observed with the more commonly used oral preparations.     

The significance of HIV antigen and HIV antibodies specific against envelope and core proteins in serum of HIV-infected hemophiliacs

Serial serum samples from the 21 HIV-infected Norwegian hemophiliacs have been assayed for the presence of HIV antigen and antibodies to HIV specific for the core protein p24 and the envelope protein gp41. HIV antigen was detected in 4 patients, of whom 3 have developed AIDS to date. HIV antigen appeared in serum 10 to 24 months before the diagnosis in these patients. Antibodies to gp41 was a constant finding. Antibodies to p24 disappeared from the serum in 1 patient who developed AIDS and from 3 persons free of symptoms related to the HIV infection. The detection of HIV antigen in HIV antibody-positive hemophiliacs appears to be of considerable prognostic significance.