Retention and clearance of 0.9-micron particles inhaled by hamsters during rest or exercise.

We assessed the retention and clearance of inhaled particles in six anatomic compartments of the respiratory tract. Hamsters were exposed for 45 min to 0.9-micron fluorescent latex particles either at rest (n = 9) or while running on a laddermill (n = 9). Oxygen consumption, which was used to estimate minute ventilation, was continuously monitored. Three animals from each group, rest and exercise, were killed at 10 min, 24 h, or 7 days after the exposure. Morphometric techniques were used to determine the number of particles retained in nose and oropharynx (NOSE), trachea and extrapulmonary airways, intrapulmonary conducting airways, respiratory bronchioles, alveolar ducts (AD), and alveoli (ALV). At 10 min, total particle retention increased linearly as a function of O2 consumption (slope = 1.4 +/- 0.3 x 10(6) particles.ml-1.g-1.h-1, P less than 0.015). Exercised hamsters retained 4.4 times more total particles in their NOSE than rested hamsters, but parenchymal retention (AD + ALV) was unaffected. After 7 days, 95% of the particles were cleared from the NOSE, 80% from the trachea and extrapulmonary airways, 44% from intrapulmonary conducting airways and respiratory bronchioles, and 16% from AD and ALV. There was evidence of particle redistribution from AD to ALV during the 1st day. We conclude that exercise enhances the deposition of 0.9-micron particles in the upper respiratory tract but not in the parenchyma. Subsequently, the deposited particles are cleared at varying rates depending on the lung compartment.

Morphometric estimation of regional differences in the rat lung.

To provide a safe basis for the sampling of tissue in future morphometric investigations of the rat lung, we searched for quantitative regional differences in pulmonary structure at light microscopic (LM) and electron microscopic (EM) levels. The lungs of 11 male rats about 6 weeks of age were fixed by standard intratracheal instillation of glutaraldehyde in the supine position and embedded either in paraffin for LM or in epoxy resin for EM investigation. Sampling of tissue was designed to test for differences between lobes and between central and peripheral lung parenchyma. LM morphometry was performed by manual point counting and by using a version of an improved automated image analyzer, Quantimet 720. EM morphometric results were obtained by manual point and intersection counting only. LM point counting showed that the proportion of parenchyma was highly constant in all lobes, varying only between 79.9% and 81.5%. In the left lung, which was partitioned into two equal halves, the amount of parenchyma was significantly lower in the apical region (mean values, 72.6% compared to 83.1%; p less than 0.002), which regularly contained the hilum. Quantimet analysis of central and subpleural lung portions revealed intralobar differences. The volume density of interalveolar septa and the air space surface density were significantly decreased in subpleural compared to central lung regions (by 7% and 4.6%, respectively). EM morphometry demonstrated that the interalveolar septa were evenly structured in all lobes except for the harmonic mean thickness of the air-blood barrier, which was lower in upper lobes. In addition, the volume density of interstitial cells was found to be significantly increased in central compared to peripheral parenchyma. The results indicate that for quantitative LM analysis the smallest possible sampling unit is an entire lobe. For EM morphometry, the often practiced approach to consider information drawn from one lobe representative for the whole lung seems to be appropriate for most parameters. In view of the structural differences between central and peripheral lung parenchyma, however, attention has to be paid to applying a properly weighted sampling procedure. Depending on the size of the lobe, the peripheral mantle (2 mm thick) can represent up to 75% of the lobar volume.

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.

The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: correlation with morphometric measurement of hepatocyte mass.

The aim of this study was to determine the prognostic significance of functional changes in the liver during progression of cirrhosis. Liver function was quantitated weekly by the aminopyrine breath test (measuring microsomal function) and the galactose breath test (measuring cytosolic function) in rats made cirrhotic by bile duct ligation (n = 14) and in sham-surgery controls (n = 9). Nine rats died spontaneously of cirrhosis. Both the aminopyrine breath test and galactose breath test were sensitive (89%) predictors of death within 1 week, but the galactose breath test was more specific (83%). Morphometric measurements of livers from surviving cirrhotic animals and controls (n = 5 each) showed that mean hepatocyte mass was maintained in the cirrhotic livers [cirrhosis (17.0 +/- 2.0) vs. controls (13.9 +/- 0.9 gm)]. The galactose breath test was also maintained, whereas the aminopyrine breath test was significantly decreased in the surviving cirrhotics. The galactose breath test, but not the aminopyrine breath test, correlated with hepatocyte mass (r = 0.67). The aminopyrine breath test correlated with microsomal aminopyrine N-demethylase activity (r = 0.78). Serial use of quantitative liver tests allows prediction of time of death from cirrhosis in this model.

The postnatal development and growth of the human lung. II. Morphology.

The morphology of postnatal human lung development and growth has been investigated by light and by scanning and transmission electron microscopy in seven children dying from non-respiratory causes and aged between 26 days and 64 months. The findings are compared with those of adult human lungs and are discussed in relation to the postnatal lung development in other species, particularly rodents. Within the first 1 1/2 postnatal years lung parenchyma undergoes a substantial structural remodeling due to bulk alveolar formation and to the restructuring of septal morphology. At one month alveolar formation appears to be well under way: The human lung is comparable then to a rat lung aged one week. In the parenchyma, numerous short and blunt tissue ridges, so-called secondary septa, subdivide the peripheral airspaces into an increasing number of still very shallow alveoli. The parenchymal septa present during and after alveolization are immature: they contain a double capillary network with a central, highly cellular sheet of connective tissue. The septal maturation sets in a few months after birth and consists of a reduction in the interstitial tissue mass and a complex process of capillary remodeling. Both alveolization and parenchymal maturation progress rapidly: by 6 months the lung has taken a big step towards maturity. By 1 1/2 years most septa show the adult structure where a single capillary network interwoven with connective tissue strands stabilizes the interalveolar wall. After the septal restructuring, lung development is considered complete, and the lung enters a period of normal growth that lasts until adulthood. From our observations we conclude that postnatal human lung development is made of two overlapping stages: (a) the alveolar stage, which starts in late fetal life and lasts to about 1-1 1/2 years, and (b) a stage of microvascular maturation, thought to extend from the first months after birth to the age of 2-3 years.

The postnatal development and growth of the human lung. I. Morphometry.

The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproportionate volume increase in the O2-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth of all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to adulthood, indicating a steady increase in the air-blood interface complexity during the entire growth period. As a consequence of the differences in growth paces between the various structural lung components in early childhood, the morphometric parameters showed large variations in their overall growth rates between birth and adulthood. Thus, the parenchymal tissue components increased by a factor of 15, lung volume and the gas-exchange surface areas between 20 and 25 times (in parallel to body mass), and, finally, the O2-transporting media, air and blood, more than 30 times. The morphometrically determined pulmonary diffusing capacity for O2 (DLO2) scaled with body mass to the power of 1.15, a value significantly different from 1. This relative improvement with age of the gas exchange function per unit body mass is due mainly to an overproportionate growth of the capillary blood compartment.

[Incapacitating spinal curvature in a skeleton discovery from the Middle Ages (7th/8th to the beginning of the 9th century). A case of probable spondylitis tuberculosa]. / Invalidisierende Wirbelsäulenverkrümmung an einem Skelettfund aus dem Frühmittelalter (7./8. bis Anfang 9. Jh.). Ein Fall einer wahrscheinlichen Spondylitis tuberculosa.

A case is presented of disability due to spondylitis of probable tuberculous etiology found in a skeleton from the early Middle Ages in Switzerland. It is suggested that the young woman had not been rejected from her family community or kinship because of her invalidity, as is thought to have often been the rule at that time.

[Intravenous injections of dissolved pentazocin tablets (Fortalgesic)--a new aspect of drug abuse in our country?]. / Intravenöse Injektion von aufgelösten Pentazocin- Tabletten (Fortalgesic)- ein neuer Aspekt des Drogenmissbrauchs auch bei uns?

A first case is reported of illicit intravenous injection of pentazocine tablets recognized in a country other than the USA. The pulmonary complications of i.v. drug abuse in general and in particular the hazards of injection of aqueous suspensions of pharmaceutical preparations intended for oral consumption, with embolization of abundant insoluble foreign material, are discussed. Diagnostic, therapeutic and prophylactic procedures are suggested.

Unusual pulmonary vascular lesions after intravenous injections of microcrystalline cellulose. A complication of pentazocine tablet abuse.

We present the morphological features of a case of fatal pulmonary granulomatosis from illicit intravenous injections of microcrystalline cellulose derived from pentazocine tablets. Extensive foreign body granulomas were found in the lumena and walls of pulmonary vessels and in the pulmonary interstitium. Previously unreported gaps containing foreign material were found in the walls of medium-sized muscular pulmonary arteries. This peculiar finding is discussed in the light of the possible mechanisms involved in the removal of embolized foreign material.