Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature.

BACKGROUND: Lactic acidosis (LA) associated with hematologic malignancies is rare, ominous, and generally occurs in adults. Its pathogenesis is poorly understood. METHODS: The authors present one case of childhood lymphoma and two cases of childhood leukemia associated with LA, and they review the available literature. Plasma concentrations of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and tumor necrosis factor (TNF)-alpha were retrospectively measured to elucidate the pathogenesis of LA. RESULTS: Lactic acidosis has been reported to date in 28 cases of lymphoma and 25 cases of leukemia, including the authors' cases. Ongoing rapid cellular proliferation was indicated in all leukemia cases. The liver was involved in 43 of the 53 cases, and hypoglycemia was present in 20. The acidosis improved only if the disease responded to chemotherapy. Remission was achieved in only five of the reported cases. In the authors' three cases, LA was associated with altered concentrations of IGFs, IGFBPs, and TNF-alpha, although causality was not established. CONCLUSIONS: Lactic acidosis in association with hematologic malignancies carries an extremely poor prognosis. Because cancer cells have a high rate of glycolysis and produce a large quantity of lactate, this condition may result from an imbalance between lactate production and hepatic lactate utilization. The authors speculate that the IGF system is involved in the pathophysiology of LA in these patients. Only chemotherapy so far has been effective in correcting the acute acidosis in a few patients; however, it has not necessarily improved ultimate outcome.

Effects of aerosolized synthetic surfactant, atovaquone, and the combination of these on murine Pneumocystis carinii pneumonia.

An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.

Characteristics associated with successful weaning in ventilator-dependent preterm infants.

Eighteen ventilator-dependent preterm infants with hyaline membrane disease were studied for 24 hours before and after an attempt at extubation. All were treated with theophylline prior to weaning and achieved average levels of 8.9 +/- 1.7 micrograms/ml (49 +/- 9 mumol/liter) in 13 successfully weaned infants and 8.4 +/- 1.1 micrograms/ml (47 +/- 6 mumol/liter) in 5 infants not extubated, p > 0.05. Infants successfully weaned were significantly (p < 0.01) older, more mature (29 +/- 1 versus 26 +/- 2 weeks' gestational age) and heavier (1107 +/- 236 versus 1016 +/- 256 gm) than infants not successfully extubated. Infants successfully weaned differed only in developing a greater maximal inspiratory force (33.8 +/- 12.3 versus 23.3 +/- 15.0 cm H2O) and higher compliance (1.1 +/- 0.3 versus 0.7 +/- 0.3) during the preweaning treatment period. These results indicate that maturity and size play a significant role in the ability to wean a preterm infant from the ventilator successfully, that maximal inspiratory force and compliance are higher in preterm infants who can be successfully extubated, and that methylxanthines do not uniformly improve pulmonary function in all potentially extubatable preterm infants.

Unilateral diaphragmatic paralysis inhibits postnatal lung growth in the piglet.

To test the hypothesis that regional growth of lung parenchyma depends on regional distending pressure, left cervical phrenectomy was done in ten 2-month-old piglets. The unilateral diaphragmatic paralysis reduced mean transpulmonary pressure in the left hemithorax from 5.5 +/- 1.0 (means +/- SD) to 2.5 +/- 1.2 cm H2O (p less than 0.01, n = 5). When five of the piglets were killed 48 h later, wet lung weight, total protein content, and nucleic acid content did not differ from values in the five sham operated controls. The five remaining phrenectomized piglets were compared to their five sham-operated controls 7 days after surgery. Wet weight of the left lung was reduced by 29% (p less than 0.01) and DNA content was reduced by 18% (p less than 0.05). Wet weight of the right lung, contralateral to the paralyzed hemidiaphragm, was reduced by 11% (p less than 0.05). At this time, body weight, bilateral transpulmonary pressure, and ratios of total protein/DNA and RNA/DNA in lung tissue did not differ from the sham-operated controls. These results suggest that regional growth of lung parenchyma by cell proliferation adjusted to changes in regional transpulmonary pressure caused by the unilateral phrenectomy.

Diaphragmatic activity is a determinant of postnatal lung growth.

To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity.