Incidence of deep vein thrombosis in bedridden non-surgical patients

In order to detect deep vein thrombosis (DVT), 101 patients with acute medical or infectious disorders were examined with the 125I-fibrinogen uptake test. All patients were bedridden on admission and were scanned daily from the second to the eighth day. Thirteen patients developed a positive fibrinogen uptake test. Thus, if a positive test is interpreted as DVT, the incidence of DVT was 13% in our bedridden patients. Of the patients admitted because of heart disease or pneumonia 20% had DVT, but only 4% of those admitted with other diagnoses. Other clinical "risk factors" studied, could not identify patients who developed DVT.     

Leakage of macromolecules from guinea-pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti-asthma drugs

The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.     

A Primary Male Autosomal Linkage Map of the Horse Genome

A primary male autosomal linkage map of the domestic horse (Equus caballus) has been developed by segregation analysis of 140 genetic markers within eight half-sib families. The family material comprised four Standardbred trotters and four Icelandic horses, with a total of 263 offspring. The marker set included 121 microsatellite markers, eight protein polymorphisms, five RFLPs, three blood group polymorphisms, two PCR–RFLPs, and one single strand conformation polymorphism (SSCP). One hundred markers were arranged into 25 linkage groups, 22 of which could be assigned physically to 18 different chromosomes (ECA1, ECA2, ECA3, ECA4, ECA5, ECA6, ECA7, ECA9, ECA10, ECA11, ECA13, ECA15, ECA16, ECA18, ECA19, ECA21, ECA22, and ECA30). The average distance between linked markers was 12.6 cM and the longest linkage group measured 103 cM. The total map distance contained within linkage groups was 679 cM. If the distances covered outside the ends of linkage groups and by unlinked markers were included, it was estimated that the marker set covered at least 1500 cM, that is, at least 50% of the genome. A comparison of the relationship between genetic and physical distances in anchored linkage groups gave ratios of 0.5–0.8 cM per Mb of DNA. This would suggest that the total male recombinational distance in the horse is 2000 cM; this value is lower than that suggested by chiasma counts. The present map should provide an important framework for future genome mapping in the horse.     

Increased levels of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) mRNA expressing blood mononuclear cells in human HIV infection.

Evidence has been presented for the involvement of IFN-gamma, IL-4 and TGF-beta in AIDS. Measured plasma levels may, however, poorly reflect in vivo production, since cytokines act auto- and paracrinally and have very short half life in plasma. In situ hybridization with complementary DNA oligonucleotide probes was used to enumerate blood mononuclear cells expressing cytokine messenger RNA (mRNA). HIV-infected patients had elevated blood levels of cells expressing each of the cytokines, with predominance for cells expressing TGF-beta mRNA. All AIDS patients included had elevated numbers of IL-4 mRNA-expressing cells, and levels of cells expressing this cytokine correlated inversely with counts of CD4+ cells in blood, reflecting the involvement of Th2-like cells in later stages of HIV infection. The described approach should be useful in further studies of cytokines in HIV infection and other diseases.     

Intracellular cytosolic free calcium concentration in the macula densa and in ascending limb cells at different luminal concentrations of sodium chloride and with added furosemide

The juxtaglomerular apparatus fulfils several important regulatory functions in the kidney, such as tubuloglomerular feedback (TGF) control and control of renin release. The macula densa (MD) cells sense the fluid load by perceiving the distal NaCl concentration via a Na-K-2Cl cotransport system in the luminal cell membrane. It has been proposed that macula densa cell activation may involve changes in intracellular cytosolic free calcium concentration ([Ca2+]i), as one link in the chain of events activating TGF or releasing renin. We therefore investigated the changes in the intracellular calcium concentrations with fura-2, using a video system, in macula densa cells, and compared them with the changes in the corresponding concentrations in the ascending limb of the loop of Henle (c-TAL). The results show that our technique for analysing intracellular cytosolic free calcium in isolated perfused tubules is valid for this purpose, and the Kd value obtained was similar to that found by Grynkiewicz et al. (1985). The intracellular cytosolic free calcium concentration was about 90 nM both in the macula densa and c-TAL cells, and the macula densa cell intracellular cytosolic free calcium concentration increased by about 20 nM when the tubular lumen was perfused with Na and Cl at low concentrations. No significant changes were noted when furosemide was added to the perfusion solutions. We consider it hardly likely that this small change in intracellular cytosolic free calcium concentration can be entirely responsible for full activation of renin release or full inactivation of the TGF control mechanism. It would seem that the signal transmission from the macula densa cells could occur by other routes than through activation of intracellular cytosolic free calcium concentration.     

Extended voluntary running inhibits exercise-induced adult hippocampal progenitor proliferation in the spontaneously hypertensive rat

Previous work has shown that voluntary running increases cell proliferation and neurogenesis in the dentate gyrus of the adult hippocampus. Here we report that long-term running for 24 days results in a down-regulation of hippocampal progenitor proliferation to one-half the level of nonrunning controls compared with a fivefold increase in progenitor proliferation seen after 9 days of voluntary running (short-term running). The negative effects seen on proliferation after 24 days of running were prevented by restricting daily running distances (by 30-50%) during 24 days. Long-term running for 24 days increases the response of the hypothalamic-pituitary-adrenal axis, with an increase in adrenal gland weight and increased plasma corticosterone levels, as well as decreased thymus weight, indicating a stress response as a possible mediator of decreased progenitor proliferation. Furthermore, the negative effects seen on the observed stress response after 24 days of running were prevented by restricting daily running distance. Short-term running did not alter these stress parameters compared with nonrunning controls. However, it increased phosphorylated cyclic AMP response element binding protein (pCREB) in the dentate gyrus, an increase that was not seen in nonrunning controls or after 24 days of running. Taken together, these data suggest that voluntary running does not always enhance proliferation and that the decrease in progenitor proliferation seen in long-term running is possibly mediated by mechanisms involving a stress response in the animal. However, a moderate level of long-term running was able to prevent the negative stress-related changes seen in unrestricted long-term running.     

Comparative studies on internalization of gold labelled mistletoe lectin I (MLI), its subunits, and of an immunotoxin into mouse L 1210V leukemia cells.

Using a preembedding electron microscopic technique, the binding and internalization of gold labelled mistletoe lectin I (MLI.Au), its 2 A subunits (MLI-A.Au) and of the B subunit (MLI-B.Au) in murine L 1210V leukemia cells was analysed. Furthermore, the endocytosis of a gold marked immunotoxin (MoAb-16-MLI-A.Au), consisting of a monoclonal antibody (MoAb-16) reacting with L 1210V cells and the cytotoxic A subunits (MLI-A) was detected. The cells were incubated with MLI.Au, MLI-A.Au, MLI-B.Au, or MoAb-16-MLI-A.Au at 37 degrees C for 1, 3, 5, 10, 20 or 30 min, respectively. Remarkable differences were found in the endocytotic pathway and internalization kinetics. The endocytosis of MLI, its subunits and of the immunotoxin has been compared to that of the other ligands in various systems.     

A simple statistical model for prediction of acute coronary syndrome in chest pain patients in the emergency department

Background  

Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED.     

Human cytomegalovirus, human herpesvirus-6 and human herpesvirus-7 in neutropenic patients with fever of unknown origin

Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 10⁹/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.