Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion.

In order to evaluate separately changes in vascular tone occurring in arteries and veins, we measured pulmonary capillary red blood cell (RBC) concentration under zone II (waterfall) conditions in isolated dog lungs rapidly frozen with Freon 12. The lungs were frozen while being perfused from artery to vein and from vein to artery breathing normal and hypoxic gas mixtures and during infusions of serotonin and histamine. Changes in capillary RBC concentration which occurred during the experimental conditions indicated an alteration in vascular resistance upstream from the capillaries. Alveolar hypoxia caused a significant decrease in capillary RBC concentration during forward perfusion, but no change from the control values during reverse perfusion. Serotonin infusion caused a decrease in RBC concentration during forward perfusion comparable with that of hypoxia and a small but significant decrease during reverse perfusion. Histamine infusion caused no change in RBC concentration from control values during forward perfusion, but a large decrease during reverse perfusion. We conclude that vasoconstriction occurs (a) exclusively in arteries during alveolar hypoxia, (b) predominantly in arteries but to a lesser extent in veins during serotonin infusion, and (c) exclusively in veins during histamine infusion.

Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome.

In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome. Acute lung injury was quantified on a four-point scoring system. At the time of entry into the study, none of the 45 patients had evidence of lung injury. Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury. The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588 +/- 204 vs. 338 +/- 196, percentage of control, P less than 0.01). Furthermore, a plasma vWf-Ag level greater than or equal to 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis. In addition, the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury. Also, a plasma vWf-Ag level greater than 450 had a positive predictive value of 80% for identifying nonsurvivors. Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value.

[Historical development of tuberculosis since Robert Koch's discovery of the tubercle bacillus in 1882]. / Die historische Entwicklung der Tuberkulose seit Robert Kochs Entdeckung des Tuberkelbazillus 1882.

Robert Koch's single-handed discovery of M. tuberculosis, one of the most gigantic scientific accomplishments of all times, provided the necessary foundation for subsequent investigative breakthroughs that have made it possible for experts to begin to contemplate the ultimate eradication of TB: the dreaded pestilence that for centuries was the greatest cause of death in the world. Further important milestones in the fight against TB were the discovery of X-rays, the development of BCG vaccination, the introduction of chemotherapy and chemoprophylaxis, and deciphering the genome of Mycobacterium tuberculosis. First of all, though, we must find a way to deal with the recent resurgence of the disease in the poor countries of sub-Saharan Africa, which is being fueled by another scourge, HIV/AIDS. And there is also the global problem of worsening anti-TB drug resistance. Eradication is conceivable and a worthy goal, but, I suspect, we will need to wait for another one or two additional "milestones" to help us along before the long-awaited nirvana can finally occur.

Melanin-concentrating hormone in peripheral circulation in the human.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role.

Evidence for a stimulatory action of melanin-concentrating hormone on luteinising hormone release involving MCH1 and melanocortin-5 receptors.

The present series of studies aimed to further our understanding of the role of melanin-concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen-primed ovariectomised rats. In rats that were steroid-primed to generate a surge-like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants. Double-label immunohistochemistry showed GnRH-immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R). Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1-R and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R and MC5-R are involved in the central control of LH release by MCH.

Benefit of amoxicillin in differentiating between TB suspects whose initial AFB sputum smears are negative.

SETTING: Out-patient dispensary in Conakry, Guinea, West Africa. OBJECTIVE: To differentiate between pulmonary tuberculosis (PTB) and non-PTB diseases among 204 acid-fast bacilli (AFB) smear-negative adult TB suspects. DESIGN: We derived scores from clinical, serological and radiological findings among PTB suspects aged > or = 15 years who, after having had three AFB-negative smears, were treated for 10 days with amoxicillin (AMX, 1.5 g/day). RESULTS: At the selected cut-off score from model 1 (clinical), sensitivity for PTB was 95%, specificity 40%, negative predictive value (NPV) 84%, and positive predictive value (PPV) 69%. Comparable values from model 2 (clinical + serological + radiological) were: sensitivity 99%, specificity 45%, NPV 97%, and PPV 71%. Results from AMX were better: sensitivity 92%, specificity 93%, NPV 94%, and PPV 91%. Of the 117 suspects who failed to respond clinically and radiographically to AMX and remained AFB smear-negative, 110 (94%) had PTB, confirmed either by positive culture (73 patients) or response to anti-tuberculosis treatment (37 patients). CONCLUSION: The clinical and radiographic response to AMX is better than derived scores at differentiating between PTB and non-PTB in TB suspects presenting to a dispensary in Guinea, a low HIV-seroprevalence country.

Leptin expression in the fetus and placenta during mouse pregnancy.

During pregnancy, leptin concentrations in the maternal circulation are elevated in both humans and rodents but decrease to pre-pregnancy levels at birth, suggesting a role for leptin in the maintenance of pregnancy. Synthesis of leptin by the human placenta is established but whether the murine placenta synthesizes leptin remains controversial. The aims of this study were to determine (a) if the mouse wild-type placenta expresses the ob gene using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and (b) whether the mouse fetus and placenta contribute to the significant increase of leptin in the maternal circulation during pregnancy. The mouse placenta did not express the ob gene at a level that could be readily detected using RT-PCR. Moreover, both maternal gain in weight and undetectable concentrations of leptin in sera in leptin-deficient ob/ob mothers bearing heterozygote (ob/+) fetuses suggested that the mouse fetus and placenta do not make a significant contribution to the dramatic increase in maternal plasma concentrations of leptin during late gestation. It is therefore concluded that neither fetal- nor placental-derived leptin modulates maternal weight gain during pregnancy.

Pulmonary complications of HIV-1 infection among adults living in Sub-Saharan Africa.

Sub-Saharan Africa, which has just over 10% of the world's population, is home to more than 25 million people living with HIV/AIDS-two thirds of the global total. Opportunistic pulmonary infections are major causes of morbidity and mortality among HIV-infected adults in the subcontinent. Of these diseases, tuberculosis (TB) is by far the most prevalent and serious, and in some countries it causes one third or more of all AIDS-related deaths. Because it is so frequent and a major public health problem, TB tops the list of differential diagnoses of people-with or without coexisting HIV infection-who present to the health care system with chronic cough and other pulmonary symptoms. As HIV-induced immunosuppression worsens, the clinical and radiographic manifestations of TB become increasingly atypical. Second among HIV/AIDS-associated pulmonary complications is community-acquired pneumonia, most commonly caused by Streptococcus pneumoniae, which usually responds to standard beta-lactam antimicrobial agents. The prevalence of Pneumocystis jirovecii pneumonia is increasing, due to both improved recognition of its characteristic clinical and radiographic features and aggressive diagnostic interventions. Treatment outcome in most countries, however, has been poor. Combined infections, usually including TB, are common. Pulmonary nocardiosis, cryptococcosis, Kaposi's sarcoma, and (possibly) histoplasmosis appear to be infrequent, but probably underdiagnosed. Improved diagnosis, treatment, and prevention of all these diseases are urgently needed, but a greatly expanded antiretroviral treatment program will help most of all.

Leptin requirement for conception, implantation, and gestation in the mouse.

The ob/ob mouse has a complete absence of circulating leptin, resulting in obesity and infertility. Using the minimum daily dose of leptin required to maintain normal body weight and sexual maturation (5 mg/kg, ip), leptin-treated ob/ob females were mated with either wild-type (+/+) or leptin-treated ob/ob males. The leptin treatment continued throughout pregnancy until weaning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum (dpc). Normal pregnancy and parturition with pups of normal weight resulted when ob/ob females were mated with +/+ males and leptin treatment was continued throughout pregnancy (6 of 8 pregnancies), to 14.5 dpc (6 of 8 pregnancies), or to 6.5 dpc (9 of 12 pregnancies). Pregnancy did not result when treatment was stopped at 3.5 dpc (1 of 7 pregnancies) or 0.5 dpc (0 of 6 pregnancies). Similar results were obtained when leptin-treated ob/ob females were mated with leptin-treated ob/ob males. The newborn pups failed to survive after birth in groups treated with leptin up to 14.5 and 6.5 dpc despite reinstating leptin at birth. This appeared to be due to a lack of development of the mammary glands. In conclusion, we have shown that leptin is essential for normal preimplantation and/or implantation processes. It is also essential for normal development of the mammary glands, but is not required for pregnancy and parturition once implantation is established.

Central orexin A has site-specific effects on luteinizing hormone release in female rats.

Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.

The value of edema fluid protein measurement in patients with pulmonary edema.

Alveolar fluid and plasma proteins were analyzed in 24 patients with florid pulmonary edema, in 21 of whom pulmonary capillary wedge pressure (Pcw) was also measured. In all patients with Pcw less than 20 mm Hg, the edema fluid to plasma protein ratio exceeded 0.6; the mean edema fluid to plasma protein ratio in the four patients with cardiogenic edema (increased Pcw) was 0.46. In the 21 patients in whom full data were available, the net intravascular filtration force (Pcw - plasma colloid osmotic pressure) was less than -4 mm Hg, the value at which (according to others) pulmonary edema should occur, in only 10. When the interstitial colloid osmotic pressure, approximated by the osmotic pressure of edema fluid protein, was added, the net filtration force became positive in 17 of 21 patients. Comparison of the protein concentrations of edema fluid and plasma aids in the diagnostic separation of increased permeability from high hydrostatic pressure edema and adds to our understanding of the relative osmotic and hydrostatic forces that contribute to pulmonary edema when the alveolar-capillary membrane is damaged.

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight.

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium 99mTc pertechnetate (TcO4), 99mTc glucoheptonate ([99mTc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), 99mTc diethylenetriaminepentaacetate ([99mTc] DTPA), 111In diethylenetriaminepentaacetate ([111In]DTPA), 67Ga desferoxaminemesylate ([67Ga]DFOM), 99mTc dextran ([99mTc]DX) and 111In transferrin ([111In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [99mTc]GH (1.50 +/- 0.37%/min), [51Cr]EDTA (2.38 +/- 1.02%/min), [99mTc]DTPA (3.51 +/- 0.40%/min), [111In]DTPA (2.35 +/- 0.42%/min), [67Ga] DFOM (1.99 +/- 0.49%/min) and [99mTc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5,099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.

Epidermal growth factor acts directly on the sheep ovary in vivo to inhibit oestradiol-17 beta and inhibin secretion and enhance progesterone secretion.

Epidermal growth factor (EGF) is a potential intra-ovarian modulator of gonadotroph action on differentiated follicular cells. Specific binding sites have been identified in the ovary and functional differentiation in cultured granulosa cells can be modulated by treatment with EGF. The aim of this study was to determine if EGF was capable of altering ovarian function in vivo during the follicular phase of the sheep oestrous cycle. Fourteen cross-bred ewes with ovarian autotransplants were treated with progestagen pessaries for 12 days. Three ewes were infused with murine EGF (mEGF) via the jugular vein (75 micrograms/kg bodyweight per 12 h) during the 12 h preceding progestagen pessary withdrawal, and received an injection of a prostaglandin analogue at 0 h to induce luteolysis. Over the same time-period, two doses of EGF were administered to other groups of ewes by infusion into the ovarian artery (low: 6 micrograms/12 h, n = 3 and high: 60 micrograms/12 h, n = 3). The remaining five ewes were not infused with EGF (controls). Jugular and ovarian venous blood samples were taken at 10-min intervals at two stages during the follicular phase (21-27 h and 38-42 h after pessary withdrawal) and every 2 h from 44 to 76 or 86 h. mEGF, LH, FSH, inhibin, androstenedione, oestradiol-17 beta and progesterone concentrations in plasma were determined using radioimmunoassays. The secretion rates of androstenedione, oestradiol, progesterone and inhibin by the ovary were calculated. EGF acted directly on the ovary in a dose-dependent manner. Oestradiol secretion was inhibited following treatment with EGF but androstenedione secretion was unaffected. EGF appears therefore to act within the granulosa cells to inhibit aromatization. Inhibin secretion was also suppressed by treatment with EGF, though it was not possible to determine if this was caused by a direct or indirect action of EGF on granulosa cells. The rate of progesterone secretion increased in ewes receiving systemic (i.e. via the jugular vein) and high-dose intra-arterial infusions of EGF, even though a preovulatory LH surge was not observed in these animals during the entire experimental period. Concomitant increases in both LH and FSH secretion were associated with these effects of EGF on ovarian function. In conclusion, EGF appears to act directly on the granulosa cells of the follicle to inhibit aromatization and also to inhibit inhibin production. The low levels of oestradiol and inhibin in the presence of high levels of gonadotrophin indicate that atresia may have been induced in medium to large antral follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of gonadal steroids on pre-pro melanin-concentrating hormone mRNA in female rats.

Melanin-concentrating hormone (MCH) may have a regulatory role in the control of luteinizing hormone (LH) release. We have investigated if gonadal steroids induce changes in the expression of pre-pro MCH (ppMCH) that are associated with changes in the pattern of LH release. Using quantitative in-situ hybridization histochemistry we have determined the effect of administration of either oestradiol benzoate (5 microg/rat) or oestradiol benzoate followed 44 or 48 h later by progesterone (0.5 mg/rat) to ovariectomized rats on the expression of ppMCH in the medial and lateral zona incerta and the lateral hypothalamus. The prevalence of ppMCH transcripts in the intact female rat at 12.00 and 19.00 h on proestrus and the first day of dioestrus was also examined. Oestrogen reduced the intensity of hybridization signal for ppMCH mRNA and this was associated with both a decrease in the number of cells in which the message was detected in the medial zona incerta and a negative feedback effect on LH release in ovariectomized rats. Progesterone administration to oestradiol benzoate-primed rats did not alter the reduced expression in the medial zona incerta in spite of its positive feedback effect on LH release. We suggest that progesterone may act only on post-translational events. Expression in the MCH cell bodies of the lateral zona incerta were not affected but there was a transient decrease 4 h after progesterone treatment in the oestradiol benzoate-primed rats in expression in the lateral hypothalamus. No changes in ppMCH mRNA were seen in intact animals on proestrus or the first day of dioestrus indicating that gonadal steroids are not important in the modulation of ppMCH gene expression during the oestrous cycle. In other steroid-dependent physiological situations, however, oestrogen may influence the expression of ppMCH in a subpopulation of cell bodies in the medial zona incerta.

Melanin-concentrating hormone, melanocortin receptors and regulation of luteinizing hormone release.

Melanin-concentrating hormone (MCH) is a neuropeptide, identified by its ability to either mimic or antagonize the melanin-dispersing action of alpha-melanocyte stimulating hormone (alphaMSH) on skin melanophores. MCH and alphaMSH also have antagonistic actions in the brain affecting feeding behaviour, aggression, anxiety, arousal and reproductive function through the release of luteinizing hormone (LH). It is not clear, however, how they exert their opposite effects in the central nervous system (CNS). One possibility is that they act via a common receptor. In this study we have examined the effect of a number of MC receptor antagonists, with relative selectivity for the MC3, 4 and 5 subtypes, on the actions of MCH on LH release. We confirmed that bilateral administration of MCH (100 and 200 ng/side) into the medial preoptic area of oestrogen-primed (oestradiol benzoate 5 microgram) ovariectomized anaesthetized rats, stimulated the release of LH. This effect was blocked by the concomitant administration into the medial preoptic area of the MC4/5 antagonist ([D-Arg8]ACTH(4-10) and the MC3/5 antagonist ([Ala6]ACTH(4-10)-both at 500 ng/side-but not by the MC3/4 antagonist, SHU9119 (200 ng/side). Furthermore, the MC3 agonist [Nle3]-gamma2 MSH failed to affect LH release. These results indicate that the MC3 and MC4 receptors are not involved in mediating the action of MCH but are consistent with an action via the MC5 subtype. Preputial glands, which express MC5 receptors, were also stimulated by MCH which is in keeping with this idea. In HEK293 cells transfected with the MC5 receptor MCH increased the production of IP3. However, it was much less potent than alphaMSH and unlike alphaMSH, had no effect on the production of cAMP. MCH (10-10 to 10-5 M) also failed to displace I125NDP-MSH from cells transfected with MC5 receptors indicating that it was not acting as a competitive antagonist and its binding site was distinct from that of alphaMSH. Thus while MCH may function as an agonist at the MC5 receptor, its stimulation of LH release is more likely to be mediated via a specific MCH receptor that has common properties with the MC5 receptor.

The effect of leptin on luteinizing hormone release is exerted in the zona incerta and mediated by melanin-concentrating hormone.

The adipose hormone, leptin, not only restrains appetite, but also influences energy expenditure. One such influence is to promote sexual maturation and fertility. The neuromodulatory circuits that mediate this effect are not well known but the present study suggests that one mediator could be melanin-concentrating hormone (MCH). We show that the long-form receptor (Ob-Rb) is expressed in the zona incerta of the rat and that administration of leptin (both 0.5 microg and 1.0 microg/side) into this area of ovariectomized, oestrogen-primed rats stimulated the release of luteinizing hormone (LH) within 1 h, the effect enduring for a further 1 h. Injections of leptin into the arcuate nucleus induced a smaller, transient rise in LH while injections into the paraventricular and ventromedial nuclei were without effect. MCH neurones are present in the zona incerta and administration of this hormone into the medial preoptic area (mPOA) stimulates LH release, therefore we investigated the possibility that MCH might mediate this effect of leptin. An injection of MCH antiserum into mPOA prevented the rise in LH normally induced by leptin injected into the zona incerta. In addition, melanocortin receptor antagonists ([D-Arg8]ACTH(4-10) and [Ala6]ACTH(4-10)), previously shown to inhibit the stimulatory effect of MCH on LH release, also inhibited the effect of leptin. We propose that one route by which leptin may promote reproductive activity is by enhancing MCH release from fibres within the mPOA. Speculative mechanisms for the action of MCH include the following possibilities: MCH may be acting on the specific MCH receptor which in turn interacts with a melanocortin or melanocortin-like receptor; MCH may bind directly to one of the melanocortin receptors; or melanocortin antagonists may interact with the MCH receptor.

Aerosolized gadolinium-DTPA enhances the magnetic resonance signal of extravascular lung water.

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), a contrast agent for magnetic resonance imaging, was administered by either aerosol or intravenous injection to rats. Proton relaxation times in excised lungs and kidneys were then measured. With increasing concentrations of aerosolized Gd-DTPA, the spin-lattice relaxation time (T1) of lungs decreased (enhanced) significantly (P less than .001), an effect that persisted for at least 80 minutes; there was no change in kidney T1. After intravenous injection of Gd-DTPA, lung T1 did not change, but kidney T1 decreased significantly (P less than .001), confirming previous observations of renal clearance. It is concluded that aerosolized Gd-DTPA is a more efficacious method of delivery of paramagnetic contrast agent to the lungs than intravenous injection, and that the lack of systemic effect after aerosolization indicates that enhancement was limited to the extravascular compartment.

Proficiency testing in immunohematology in Ontario, Canada, 1975-1977.

Since April 1975 the proficiency of laboratories in Ontario that perform immunohematology tests has been assessed. While the majority of test samples have required only ABO and Rh(D) typing, others have posed problems. The error rate in uncomplicated ABO typing was 1.3/1,000 in 17,479 tests and that in straightforward Rh(D) grouping, 6.6/1,000 in 17,757 tests. False-negative (36/1,000) and false-positive (1.4/1,000) direct antiglobulin tests occurred. Errors in detection of strong alloantibodies (e.g., anti-D) were 19.7, 10.2 and 5.1/1,000 in three test samples. A2B or A2 cells with anti-A1 in serum were sent out in two surveys; error rates in ABO interpretation were 189 and 52/1,000, respectively. Laboratories also experienced difficulty in interpreting the Rh(D) type of cells with positive antiglobulin tests. These surveys have had several effects: (1) laboratories with poor performance have been identified, (2) patterns of practice have been influenced, (3) areas of ignorance have been identified, and (4) a stimulus has been provided for continuing education in immunohematology.

Rebreathing lung tissue volume of sheep with normal and edematous lungs.

To determine the accuracy of measurements of lung tissue volume (Vlt) by rebreathing acetylene in normal and edematous lungs, we compared gravimetric values of total lung weight (Ql) and extravascular lung water (Qwl) with Vlt in anesthetized control sheep (C) and sheep with hydrostatic pulmonary edema (HPE) or oleic acid-induced permeability pulmonary edema (PPE), five animals each. In eight additional sheep we determined that acetylene solubility in blood (0.117 +/- 0.010 ml X 100 ml-1 X Torr-1) differed significantly from that in lung-blood homogenates (0.095 +/- 0.009 ml X 100 ml-1 X Torr-1, P = 0.0017). The latter value was used in all calculations. In C, Vlt was 194% of Qwl and 98% of Ql; in HPE, Vlt was 144% of Qwl and 87% of Ql; and in PPE, Vlt was 112% of Qwl and 77% of Ql. We conclude that when the lungs are normal, Vlt reasonably measures Ql not Qwl. However in both HPE and PPE, Vlt progressively underestimates Ql and cannot differentiate between increased blood volume and increased Qwl.