Calcified subcutaneous arterioles with infarcts of the subcutis and skin ("calciphylaxis") in chronic renal failure.

Patients with chronic renal failure (CRF) are at increased risk for pathological calcifications because of increased serum calcium-phosphorus products. A minority, including those undergoing dialysis, develop a syndrome of deep skin ulcerations in association with calcification of subcutaneous arterioles. The body distribution of the skin lesions may be proximal (central), distal (peripheral), or both. Since 1968, this syndrome has been called "calciphylaxis" in the belief that it is the human analogue of Selye's experimental models of tissue calcification. Our review emphasizes that this syndrome comprises two separate processes not found in calciphylaxis: calcification of subcutaneous arterioles and infarctions of subcutaneous adipose tissue (panniculus adiposus) and skin. The infarctions are acute and clinically dramatic, whereas the calcific arteriolopathy is preexistent, having developed slowly, sometimes over years, and silently. Separating these two processes facilitates analyses of pathogenetic factors, such as those that target subcutaneous arterioles for calcification and those that interfere with blood flow through the calcified arterioles, sufficient in some patients to cause the infarctions, and of why obesity in CRF is a syndrome risk factor. This approach further helps to provide a much needed standardized definition of the syndrome, thereby facilitating comparisons of the results of such treatments as parathyroidectomy, anticoagulants, and phosphate binders. Finally, the separation shows why the application of such terms as calciphylaxis and calcifying panniculitis to this syndrome is inappropriate.

Bronchiolitis obliterans in a man who used his wood-burning stove to burn synthetic construction materials.

Many people heat their homes with wood-burning stoves. However, toxic fire effluent can escape from old or improperly operated stoves. The authors describe a case in which bronchiolitis obliterans developed in a man within hours after he burned synthetic construction materials in his wood-burning stove. Certain factors, such as careless or improper use of the stove, the size of the room, the lack of open-air ventilation and the composition of the materials burned, strongly point to inhalation of the fire effluent as the cause.

Skin necrosis: an unusual complication of hyperphosphatemia during total parenteral nutrition therapy.

BACKGROUND: Hyperphosphatemia complicated by calcification of subcutaneous arteries and skin infarcts are very rarely reported in the absence of chronic renal failure (CRF). We describe identical lesions in an obese woman with sepsis. Hyperphosphatemia resulted from an unintended excess of phosphate in her total parenteral nutrition (TPN) formulations. She did not have CRF or hyperparathyroidism. METHODS: The patient's records during 37 weeks of hospitalization 12 years ago and, subsequently, her outpatient records were reviewed. RESULTS: During a 7-week period, the total elemental phosphorus infused daily, as divalent phosphate, ranged from 1.8 to 4.2 g, median 3.1, over triple the normal daily requirement. This excess was unintended. This occurred before the current practice of pharmacist-monitoring of TPN formulations, and possibly resulted from misinterpretation of a revised formulation sheet, newly introduced to the nursing units at the start of that period. Serum phosphorus increased to 3.02 mmol/L (normal 0.76 to 1.46 mmol/L). She developed calcification of subcutaneous arteries, which was complicated by widespread infarcts of the anatomically related skin and subcutis, apparently the result of hypoperfusion of these vessels during an episode of septic shock. The infarcts were heralded by unusual, blotchy skin discolorations. CONCLUSIONS: This report, illustrating a startling cutaneous complication associated with apparent misinterpretation of TPN formulations, demonstrates a pathogenetic relationship between hyperphosphatemia, calcification of subcutaneous arteries, and necrosis of the skin and subcutis in the absence of CRF and hyperparathyroidism and introduces a new differential diagnosis for unusual skin lesions appearing during TPN therapy.

Breast infarction in a patient with chronic renal failure: a case report.

A 41-year-old woman who had chronic renal failure required a simple mastectomy for infarction of one breast. On initial presentation her condition was managed as a skin ulcer. Arterial calcification is common in chronic renal failure and its pathogenetic connection with this uncommon event is relevant to the management of "skin ulcers" in general in this population.

Subcutaneous microvascular (capillary) calcification. Another basis for livedo-like skin changes?

A morbidly obese woman with acute renal failure, high serum phosphorus and slightly depressed serum calcium levels, developed areas of induration in the subcutis with associated livedo reticularis. Later, the subcutis became necrotic and the skin ulcerated. The arterioles, and notably widened occluded capillaries, were found to contain calcium and phosphorus as determined by energy dispersive spectrometry. X-ray diffraction of the subcutis in an early stage of this lesion showed that the mineral was most likely a poorly crystalline hydroxyapatite.

Effects of smoke inhalation on alveolar surfactant subtypes in mice.

The effects of smoke inhalation on alveolar surfactant subtypes were examined in mice exposed for 30 minutes to smoke generated from the burning of a flexible polyurethane foam. At 4 or 12 hours after the exposure, three surfactant pellets, P10, P60, and P100, and a supernatant, S100, were prepared by sequential centrifugation of lavage fluids at 10,000 g for 30 minutes (P10), 60,000 g for 60 minutes (P60), and 100,000 g for 15 hours (P100 and S100). Phospholipid analysis and electron microscopy were performed on each fraction. Smoke exposure dramatically altered the normal distributions of these fractions: it significantly increased the phospholipid content of the heavier subtype, P10, which is thought to represent newly secreted surfactant; had no effect on the intermediate form, P60; and dramatically increased the phospholipid content (approximately fivefold) of the lighter subtypes, P100 and S100, which are believed to represent catabolic end-products of alveolar surfactant. Only P100 was structurally altered by the smoke. These results represent alterations of the normal metabolic processing of alveolar surfactant. Whereas the mechanism is yet to be defined, it seems to involve a small but significant increase in the newly secreted surfactant, as well as an excessively high accumulation of the structurally altered catabolic forms of the secreted surfactant.

The value of open lung biopsy in immunocompetent patients with community-acquired pneumonia requiring hospitalization.

OBJECTIVE: To determine the role of open lung biopsy in immunocompetent patients with community-acquired pneumonia who require hospitalization. DESIGN: A group of 1,118 patients with severe community-acquired pneumonia that required hospitalization were enrolled in the study. Of the patients, 26 underwent open lung biopsy. Another 18 of these patients were immunocompromised and were excluded from this segment of the study. SETTING: Tertiary care 800-bed hospital from November 1981 to May 1989. RESULTS: Progressive diffuse pulmonary infiltrates and negative conventional cultures were the indications for biopsy in most of these patients. Eighteen (69 percent) were immunocompromised. The eight immunocompetent patients underwent a retrospective review of their course in hospital. Three patients died. The diagnostic yield from open lung biopsy was 25 percent. A specific histologic diagnosis was made in one patient--lipoid pneumonia. The pulmonary histologic finding were nonspecific in the remaining patients, but in four, in combination with the clinical data, gave useful information and resulted in therapy change. Culture of a pulmonary tissue yielded cytomegalovirus in one other patient. Serologic testing had a low yield in this group with three patients having a positive result. CONCLUSIONS: Open lung biopsy is rarely necessary in immunocompetent patients with community-acquired pneumonia. In a small group of patients where it is necessary, however, both positive and negative results are important in directing therapy.

Lung injury after experimental smoke inhalation: particle-associated changes in alveolar macrophages.

The role of smoke particles in the pathogenesis of smoke inhalation lung injury is enigmatic. We report an experimental model that facilitates study of this issue. Mice were exposed over a 30-min period to smoke released from a flexible polyurethane foam, heated at 400 degrees C. The smoke was initially rich in spherical, isocyanate-containing particles of respirable sizes. Respirations were labored at the end of the exposure and worsened with time and were accompanied by increases in lung water. Bronchoalveolar lavage revealed a significant reduction in the total number of alveolar macrophages in the fluid recovered from the lungs as early as 2 hr after exposure. Macrophage cytoplasm contained numerous smoke particles and decreased numbers of lysosomal-like granules, and the nuclei were often pyknotic. The same recovered lavage fluid contained numerous smoke particles, free lysosomal-like granules, cytoplasmic and nuclear debris, and significant increases in the soluble activity of both the lysosomal marker enzyme and total protein. These findings indicate that there was cell breakdown, including macrophages. Free-radical isocyanates are toxic compounds, and we suggest that after being phagocytized these compounds contribute to the breakdown of macrophages. A pathogenic relationship between these macrophage changes and the acute lung injury can next be explored in this model.

Structural changes in the subcutaneous compartment in morbid obesity.

Most of the excess fat that accumulates in the morbidly obese is accommodated in the subcutaneous compartment (SCC), specifically in the adipose tissue lobules of the panniculus adiposus which enlarge and expand the SCC. However, the fibroelastic septa that are attached to the skin on one side of the SCC and to the deep fascia on the other invest each lobule and thereby offer resistance to the enlarging lobules. We report observations made during pathologic examinations of the abdominal wall SCC that were surgically excised by abdominal dermo-panniculectomy from 48 morbidly obese subjects after gastroplasty and weight loss. Lobules were large but varied notably upwards in size and, to some extent, shape. Simultaneously upon incision of the SCC, the lobules bulged above and the septa retracted below the same cut surfaces. Light microscopy revealed disruptions of septal elastic fibers, calcification of septa and septal arteries and necrosis of adipocytes, all sparsely distributed. Certain questions and facts emerge from these observations. Are the variations in lobule sizes normal, or do they reflect uneven fat deposition or mobilization during weight gain or loss respectively? Is there any correlation between lobule and adipocyte sizes? The tightly coupled phenomena of lobule-bulging and septal-retraction indicate that the lobules and septa are subjected to compressional and tensile stresses respectively in the intact, non-incised SCC. The histologic changes might be consequences of these stresses. Studies of the variations in body fat distribution and in adipocyte size have contributed to an understanding of obesity pathogenesis. The relevance of the present findings is unknown at this time, but these appear to have potential implications for studies of the morphogenesis of obesity. Confirmation of these findings, particularly the lobule variations, is required so that these can be compared with those in never-obese subjects and in morbidly obese subjects without prior weight loss.

Mouse alveolar surfactant: characterization of subtypes prepared by differential centrifugation.

To characterize the properties of alveolar surfactant subfractions obtained from mouse lung by differential centrifugation, lavage fluid, following a preliminary centrifugation at 140 x g for 5 min to yield a cellular pellet (Pc), was sequentially centrifuged at 10,000 x g for 30 min, 60,000 x g for 60 min and 100,000 x g for 15 h; and the resultant pellets, respectively referred to as P10, P60 and P100, were harvested for electron microscopy, phospholipid analysis and surface tension measurements. Ultrastructural differences were observed, in that P10 contained large multilamellated structures which were typical of newly secreted surfactant, P100 contained small unilamellar vesicular structures, typical of catabolic end products of alveolar surfactant and P60 appeared to contain a mixture of structures present in P10 and P100 in addition to numerous, large unilamellar vesicles which were not present in either P10 or P100. Slight but significant differences were found in the phospholipid compositions of the three subfractions but not in the fatty acid composition of their phosphatidylcholine (PC) component. There were no significant differences in their disaturated PC/total PC ratios, but significant differences in their phospholipid/protein ratios. P60 had the highest proportion of phospholipid to protein. P10 and P60 demonstrated surface activity but P100 did not. Total alveolar surfactant phospholipid was evenly distributed among the three fractions. This pattern of distribution was significantly different from that observed in rabbit subfractions prepared by the same procedure. These data indicate that mouse alveolar surfactant consists of three distinct subfractions or subtypes which can be separately and quantitatively isolated by differential centrifugation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute skin and fat necrosis during sepsis in a patient with chronic renal failure and subcutaneous arterial calcification.

Calcification of small subcutaneous arteries and arterioles is commonly found in patients with chronic renal failure (CRF), but the syndrome of acute ischemic necrosis of the skin and subcutaneous fat supplied by these vessels is relatively uncommon. The necrosis occurs during dialysis and after successful renal transplantation, and it is often fatal. Occlusion of the calcified arteries and associated microvessels by thrombi is reported infrequently, but it is relevant to the necrosis. However, the pathogenesis remains enigmatic. In the patient described here, who had CRF, bacteremia, and laboratory evidence of disseminated intravascular coagulation (DIC), the distribution of thrombi and necrosis was mainly that of the calcified arteries which, therefore, probably played a role in the localization of the thrombi. An increased susceptibility of the endothelium of calcified vessels to the procoagulant effects of sepsis may be a contributing factor.

Effects of smoke inhalation on surfactant phospholipids and phospholipase A2 activity in the mouse lung.

The effects of smoke inhalation on the pulmonary surfactant system were examined in mice exposed for 30 minutes to smoke generated from the burning of polyurethane foam. At 8 or 12 hours after exposure, surfactants were isolated separately from lung lavage (extracellular surfactant) and residual lung tissue (intracellular surfactant) for phospholipid analysis. Calcium-dependent phospholipase A2 (PLA2) was measured on a microsomal fraction prepared from the tissue homogenate. Smoke inhalation produced a twofold increase in extracellular surfactant total phospholipid. While there was no change in the total phospholipid or phosphatidylcholine (PC) content of the intracellular surfactant, smoke inhalation significantly decreased the disaturated species of PC (DSPC). The specific activity of PLA2 was reduced by more than 50% in both groups of exposed mice. Smoke inhalation appears to result in selective depletion of the DSPC of intracellular surfactant and PLA2 involved in its synthesis. This depletion may be compensated for by increased secretion or slower breakdown of the material present in the extracellular compartment.

Fatal pulmonary edema due to nitric acid fume inhalation in three pulp-mill workers.

Three young men died of rapidly progressive pulmonary edema of delayed onset after inhalation of fumes from an accidental nitric acid explosion. Electron microscopy revealed altered neutrophils and necrotic endothelial cells in alveolar capillaries. Immunohistochemistry showed small and large serum proteins, including immunoglobulin M, in the edema fluid and hyaline membranes. Increased permeability is a consequence of direct microvascular injury by inhaled nitrogen dioxide. However, our findings, implicating neutrophils and serum-derived mediators in the pathogenesis of the pulmonary edema, are consistent with recent proposals on their roles in the maintenance and/or progression of edema initiated by toxic inhalations.

Delayed sequelae of pulmonary barotrauma.

Progression of cystic changes in the lung, with development of pneumothoraces long after withdrawal of ventilatory support, was observed in two patients who recovered from adult respiratory distress syndrome. On pathologic examination both pleural and parenchymal cysts were confirmed.

Use of a fluid dispensing apparatus for bronchoalveolar lavage in mice.

The volume of the mouse lung is small, so bronchoalveolar lavage (BAL) in mice is generally performed with 1 ml syringes to infuse smaller volumes of fluid. Multiple infusions are required to obtain enough recovered fluid for multiple analyses. This paper introduces the use of one type of a simple fluid dispensing apparatus as an infusion device. It proved to be a faster and a less tedious method than the syringe infusion method. The results of studies in normal mice using both infusion techniques showed no differences between the two with respect to the recovery of cells and protein and to differential leukocyte counts. Thus, the results obtained with this device can be compared with those previously obtained with syringes.

Cardiac angiosarcomas. A review and a case report.

Forty-five cases of cardiac angiosarcomas were reviewed, and the data were compared with those of a 1968 review of 41 other cases which revealed these tumors to be typically located within the right atrium as large symptomatic masses and to be rapidly fatal, with the diagnoses usually determined only at autopsy. The relationship of these tumors to Kaposi's sarcoma was also examined. The findings paralleled those of the previous review. Additionally, the following points emerged: With the aid of newer imaging techniques, localization, biopsy diagnosis and resection of the atrial tumors are now being achieved more often, with some improvement in survival. Like angiosarcomas of other organs, atrial angiosarcomas exhibit highly variable histologic patterns, which often overlap those of Kaposi's sarcoma, and may also present metastatic patterns simulating widespread Kaposi's sarcoma or malignant melanoma. In reported cases of classical, endemic, or epidemic Kaposi's sarcoma, cardiac lesions are uncommon and typically are small, asymptomatic, restricted to the epicardium/or pericardium and, thus, are clearly different, both clinically and pathologically, from the atrial tumor group. The justification for designating cases of the latter group as "primary cardiac Kaposi's sarcoma" is open to debate. A case report illustrates many of the above points.

Does cytomegalovirus play a role in community-acquired pneumonia?

Cytomegalovirus (CMV) is recognized as an important pathogen in the immuno-suppressed patient. Sporadic case reports of cytomegalovirus community-acquired pneumonia have appeared. We studied 443 patients with community-acquired pneumonia requiring hospitalization to define the role of cytomegalovirus in this illness. Four patients (0.9%) had good evidence that cytomegalovirus caused their pneumonia: 2 had the virus isolated from pulmonary tissue and 2 had cytomegalovirus inclusion bodies visualized in this tissue. An additional 14 patients had serologic evidence (a fourfold rise in the complement fixation tests) of cytomegalovirus infection. Analysis of these 18 patients suggest, that cytomegalovirus plays a role in community-acquired pneumonia. Six (33%) of the patients were immunosuppressed. Six others had concomitant infections: Chlamydia trachomatis (3); Epstein-Barr virus and M. pneumoniae (1); and bacteremia with Group B streptococcus and Bacteroides fragilis plus Eubacterium lentum (1 each). Seven patients (39%) required assisted ventilation, four of whom developed secondary bacterial pneumonia. Five (28%) died. Only two patients had a clinical and radiographic picture suggestive of a viral illness as a cause of the pneumonia. Three patients had atypical lymphocytes in their peripheral blood film. We found that the prevalence of complement fixing antibody to cytomegalovirus increased with age. Such antibody was lacking among those in the 16-20 year group while it peaked at 65% for males and at 78% for females ages 91-100 years. Despite the fact that 42.2% of the adults lacked antibody to cytomegalovirus, community-acquired pneumonia due to this virus is uncommon and does not justify routine serological testing for such infection among patients with community-acquired pneumonia.

Pneumonia in renal transplant patients.

Between January 1976 and March 1982, 28 episodes of pneumonia occurred in 26 renal transplant patients. The overall mortality rate was 46%. Of the 16 patients with nosocomial pneumonia 9 (56%) died, whereas of the 12 patients with community-acquired pneumonia 4 (33%) died. In all 9 cases of unknown cause the response to empiric treatment was prompt, whereas in 4 of the 10 cases of monomicrobial pneumonia and 8 of the 9 cases of polymicrobial pneumonia the patient died. Cytomegalovirus was the sole cause of the pneumonia in two patients and a contributing cause, along with aerobic gram-negative bacteria, in another five, four of whom also had a fungal infection. Two patients, both of whom survived, had nosocomial Legionnaires' disease.