Irreversible shock of rats after acute renal vein thrombosis

Summary After occlusion of the renal veins rats die quickly in progressive shock (within 4.5 h), but after ligating the renal hilum of both Kidneys they survive 27 h. To learn why renal vein occlusion is so rapidly lethal, and what substances are given off and by what method from the hemorrhagically infarcted kidneys, we studied eight groups of rats, each containing at least seven animals. The groups differed in the combination of hilar structures (renal veins, ureters, lymphatics) ligated. We compared: survival times, changes in blood pressure, blood volume, levels of plasma kinins, adenosine, and lactate, changes of blood pH, responses to Indomethacin, Trasylol^®, and plasma expanders, tubular and capillary flow rates, histopathological changes in organs and cerebral blood flow and changes in the blood coagulation system. Our results suggest that the venous stasis, anoxia, and hemorrhagic necrosis caused by bilateral venous occlusion release into renal lymphatics toxic substances which reach the systemic circulation and induce irreversible shock. We have excluded prostaglandins and adenosine as the toxic substances inducing shock but could not rule out an action of the kallikrein-kinin-system. We postulate that the striking degenerative changes occurring in the arterioles of the brain after bilateral venous occlusion may mean these vessels are especially susceptible to high levels of lactic acid and that this may explain why these animals die so quickly. Our conclusions should help not only in understanding why high levels of lactate in shock portend a poor prognosis but also help in formulating appropriate therapy for circulatory failure of renal origin and for protracted hypotension after extensive tissue injury.The studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres SystemPresented in part: Jäckh and Steinhausen, 1976; Dallenbach et al., 1978; Zimmerhackl et al., 1979We dedicate this paper to Wilhelm Doerr, Dr. med., Professor of Pathology, University of Heidelberg on the occasion of his 65th birthday (August 25th, 1979)     

Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene

Individuals affected by the autosomal recessive disease xerodermapigmentosum (XP) are acutely sensitive to sunlight and predisposedto skin cancer on exposed areas. Cells cultured from XP patientsare both UV sensitive and defective in the nucleotide excisionrepair of damaged DNA. These cellular phenotypes are amenableto experimental strategies employing complementation, an approachpreviously used to demonstrate the correction of XP-D phenotypesfollowing the introduction of the XPD (ERCC2) gene. In the presentstudy, we have characterized the genomic organization of theXPD (ERCC2) gene and found it to be comprised of 23 exons. Thesedata were helpful in evaluating the functional integrity ofalleles in two XP-D cell lines. In cell line GM436 a C     

HIV testing within at-risk populations in the United States and the reasons for seeking or avoiding HIV testing

OBJECTIVES: We determined proportions of high-risk persons tested for HIV, the reasons for testing and not testing, and attitudes and perceptions regarding HIV testing, information that is critical for planning prevention programs. METHODS: Cross-sectional interview study of persons at high risk for HIV infection (men who have sex with men [MSM]; injection drug users [IDUs]; and heterosexual persons recruited from gay bars, street outreach, and sexually transmitted disease clinics) among six states participating in the HIV Testing Survey (HITS) in 1995 to 1996 (HITS-I) and 1998 to 1999 (HITS-II). RESULTS: Overall testing rates were lower in the HITS-I (1226/1599 [77%]) than in the HITS-II (1375/1711 [80%]) (p =.01). Persons <25 years old tested less frequently than those >or=25 years old (HITS-I: 71% vs. 78%, respectively, p=.007; HITS-II: 63% vs. 85%, respectively, p<.001). The main reasons for testing and not testing were the same in both surveys, but the proportions of reasons for not testing differed (e.g., "unlikely exposed to HIV" [HITS-I (17%) vs. HITS-II (30%), p<.0001], "afraid of finding out HIV-positive" [HITS-I (27%) vs. HITS-II (18%), p<.0001]). Attitudes regarding HIV testing differed among tested and untested respondents, especially among MSM. CONCLUSIONS: HIV testing rates were higher in the HITS-II, but testing rates decreased among the youngest respondents. Denial of HIV risk factors and fear of being HIV-positive were the principal reasons for not being tested. Availability of new HIV therapies may have contributed to decreased fear of finding out that one is HIV infected as a reason to avoid testing. The increased proportion of persons at risk who did not test because they believed they were unlikely to have been exposed highlights the need for prevention efforts to address risk perceptions.     

Opioid receptors regulate the extinction of Pavlovian fear conditioning

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation.     

Operative morbidity and reproductive outcome in secondary myomectomy: a prospective cohort study

BACKGROUND: This prospective study was designed to evaluate the operative morbidity and reproductive outcome in patients who had secondary myomectomy for recurrent symptomatic uterine fibroids. METHODS: A total of 58 women were subjected to a secondary myomectomy via the abdominal route. The operative morbidity such as blood loss, presence of adhesions and febrile index were estimated and the pregnancy outcome over a 2-4 year period of follow-up. RESULTS: The mean age and standard deviation (+/- SD) of the women was 35 (+/- 2.4) years. Nineteen patients (33%) had a postoperative temperature vertical line 100 degrees F and the estimated blood loss ranged from 159-2500 ml (median 700 ml). Seven patients (12%) required blood transfusion and one had a hysterectomy due to haemorrhage. Nine women (15.5%) became pregnant but only five (56%) had live births. Those with successful pregnancies tended to be younger with a mean age of 31.8 (+/- 2.6) years versus 35 (+/- 1.8) years, (P = 0.08, non-significant) and had fewer uterine leiomyomata; median with range values, 2 (1-6) versus 7 (6-15). The variables which best predicted the postoperative likelihood of pregnancy were; age, presence of tubal adhesions and the number of uterine fibroids. CONCLUSION: This prospective study showed a high operative morbidity and a poor fertility outcome after a repeat myomectomy. The factors affecting successful outcome in a logistic regression model were age, tubal adhesions and number of uterine fibroids.     

Aneuploidy in recurrent spontaneous aborters: the tendency to parental nondisjunction

To test the hypothesis that parental aneuploidy, particularly involving sex chromosomes, indicates an increased risk of meiotic nondisjunction, we analyzed chromosome numbers from 283 parents who had had 2 or more spontaneous abortions and, if they had children, no abnormal offspring. A sample of 15 lymphocyte metaphases was examined per individual for a total of 4,245 metaphases. Two or more cells with the same abnormal chromosome complement were found in 19 individuals: 4 males with a minor number of 45, X cells and 15 females with minor numbers of 45, X and/or 47, XXX cells (p< 0.001). The most logical explanation is that mitosis may, in part, reflect meiosis. This group of parents appears predisposed to chromosome errors in meiosis leading to recurrent spontaneous abortion.     

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2007.

Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years.     

Cytochemical localization of tartrate-resistant acid phosphatase,alkaline phosphatase,and nonspecific esterase in perivascular cells of cartilage canals in the developing mouse epiphysis

Cytochemical localization of tartrate-resistant acid phosphatase (TRAP), tartratc-sensitive acid phosphatases (TSAP), alkaline phosphatase, and nonspecific esterase was used to characterize perivascular cells within cartilage canals. In the distal femoral epiphyses of 5- to 7-day-old mice, three stages of canal development can be distinguished, and at each developmental stage different perivascular cells were present with morphological characteristics of degradative cells. Vacuolated cells resembling macrophages, fibroblastic cells, and chondroclasts were present adjacent to the matrix in superficial, intermediate, and deep canals, respectively. In order to characterize these perivascular cells cytochemically, nonspecific esterase and TSAP staining was used to identify macrophages, alkaline phosphatase staining was used to identify fibroblastic cells, and TRAP staining was used to identify chondroclasts. There were no cells present in the canals at any developmental stage that were positive for TSAP or strongly positive for nonspecific esterase, placing doubt on the identity of the vacuolated cells as macrophages. Alkaline phosohatase-positive perivascular cells were present in the intermediate and deep canals adjacant to matrix containing alkaline phosphatase-positive chondrocytes. These alkaline phosphatase-positive cells were found in the same location within canals as the fibroblastic cells. Tartrate-resislant acid phosphatase was localized in chondroclasts at the tips of deep canals but was not confined exclusively to chondroclasts. Except for the very early stage of canal development prior to chondrocyte hypertrophy, TRAP-positive cells were present at the tips of superficial and intermediate canals as well as at the tips of the deep canals. Additionally, the presence of TRAP in chondrocytes with in the growth plate, in chondrocytes within the epiphyseal cartilage near some canals, and in perichondrial cells suggests that TRAP is associated with matrix degradation in the cartilage.