Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Among 80 women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (40 with the simple virilizing form and 40 with the salt-losing form), 40 reported having an adequate introitus and being heterosexually active. In 15 of 25 patients with the simple virilizing form, 25 pregnancies resulted in 20 normal children, whereas only 1 of 15 women with the salt-losing form became pregnant; this pregnancy was electively terminated. Several factors seem to be responsible for the low fertility rates: noncompliance with therapy was probably high, as suggested by hirsutism and poor endocrine follow-up in 25 percent of patients; whereas 49 patients had regular menstrual periods, 14 had irregular periods, 10 had amenorrhea, 5 had undergone hysterectomy, and 2 had entered menopause; 87 percent of patients with salt loss and 50 percent of those with simple virilization (P less than 0.001) had remained single; the vaginal introitus was reported to be inadequate for intercourse by 35 percent of patients (53 percent of those with salt loss and 18 percent of those with simple virilization; P less than 0.002); and heterosexual activity was reported less frequently among patients with an inadequate introitus. The status of the introitus seemed to have a more important role in the sexual activity reported than did the degree of prenatal exposure to androgen (which was higher among patients with salt loss than among those with simple virilization). However, our data did not rule out an effect of androgen exposure on female fetuses. Our experience indicates that improved surgical correction of the external genitalia and better compliance with therapy will be necessary to improve fertility rates among women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.     

Cross-presentation: underlying mechanisms and role in immune surveillance

Summary: It was originally thought that a cell's major histocompatibility complex (MHC) class I molecules presented peptides derived exclusively from proteins synthesized by the cell itself. However, in some circumstances, antigens from the extracellular environment can be presented on MHC class I molecules and stimulate CD8⁺ T‐cell immunity, a process termed cross‐presentation. Cross‐presentation was originally discovered as an obscure phenomenon in transplantation immunity. However, it is now clear that it is a major mechanism by which the immune system monitors tissues and phagocytes for the presence of foreign antigen. Cross‐presentation is the only pathway by which the immune system can detect and respond to viral infections or mutations that exclusively occur in parenchymal cells rather than in bone marrow‐derived antigen‐presenting cells (APCs). Professional APCs, such as dendritic cells, are the principal cells endowed with the capacity to cross‐present antigens. In this process, the APCs acquire proteins from other tissue cells through endocytic mechanisms, especially phagocytosis or macropinocytosis. The internalized antigen can then be processed through at least two different mechanisms. In one pathway, the antigen is transferred from the phagosome into the cytosol, where it is hydrolyzed by proteasomes into oligopeptides that are then transported by the transporter associated with antigen processing to MHC class I molecules in the endoplasmic reticulum or phagosomes. In a second pathway, the antigen is cleaved into peptides by endosomal proteases, particularly cathepsin S, and bound by class I molecules probably in the endocytic compartment itself. Depending on the nature of the antigen, one or both of these pathways can contribute to cross‐presentation in vivo. The outcome of cross‐presentation can be either tolerance or immunity. Which of these outcomes occurs is thought to depend on whether antigens are acquired by themselves alone, leading to tolerance, or with immunostimulatory signals, leading to immunity. One source of such signals is from dying cells that release immunostimulatory ‘danger’ signals that promote the generation of immunity to their cellular antigens. In addition to the critical role of cross‐presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4⁺ and CD8⁺ T‐cell immunity.     

MR technology: effect of even-echo rephasing on calculated T2 values and T2 images

In multiple spin-echo image sequences of blood flow, the "even-echo" phenomenon produces an absolute increase in signal magnitude from first- to second-echo images of normal vessels harboring slow flow. Distinguishing this from the apparent relatively high signal intensity seen on second-echo images in pathologic foci of stationary tissue is important to the diagnostician. Selected case material containing two tissue types was reviewed retrospectively: tissues known to harbor slow flow, such as normal veins and venous sinuses and vascular malformations, and tissues that have long transverse (T2) relaxation times and appear as intense structures on second-echo images, such as neoplasms, infarcts, and regions of demyelination. Calculations of T2 parameters were made by computer for defined regions of interest. T2 images were also generated. Visual inspection of the acquired images did not reliably distinguish increased intensity due to even-echo rephasing from the relative changes between adjacent tissues seen on second-echo images. More definitive differentiation of the even-echo phenomenon was provided by calculated values of T2 and computer-synthesized T2 images representing acquired intensity data of two-echo sequences. The synthesized images were especially useful when stationary tissue with lengthened T2 values was adjacent to or in proximity to vessels or vascular lesions. A five spin-echo image sequence was valuable for separating slow flow from stationary tissue by a technique of synthesizing T2-difference images using three consecutive echoes.     

Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m)

In a previous controlled study, dexamethasone (DEX) was shown to prevent acute mountain sickness (AMS) during exposure to simulated high altitude. To determine the effect of DEX during actual altitude exposure, 16 young men were treated with either DEX (4 mg every 6 h) or placebo for 48 h prior to and 48 h after being rapidly transported from sea level to the summit of Pikes Peak, CO (4,300 m). Symptoms of AMS were evaluated twice daily at Pikes Peak using the Environmental Symptoms Questionnaire and a clinical assessment. During treatment the mean symptom scores were higher for subjects taking placebo in 18 out of 20 comparisons. On an individual basis, 60% of the subjects receiving placebo met the criteria for being "sick" compared to 31% of subjects receiving DEX. Beginning 24 h after cessation of treatment, DEX subjects experienced a progressive increase in symptom scores which lasted through the end of the altitude sojourn (day 6). The results indicate that DEX is an effective prophylactic treatment for AMS in an actual mountain environment, but that AMS symptoms can occur if the drug is stopped abruptly.     

Despite Equivalent Outcomes,Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer

Annals of Surgical Oncology -     

Halothane alters the oxygen consumption-oxygen delivery relationship compared with conscious state

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.