Cellular energy metabolism during fetal development. II. Fatty acid oxidation by the developing heart.

In view of the importance of fatty acids as substrates for the mature heart, fatty acid oxidation by fetal and calf heart mitochondria has been investigated. Free fatty acids of 10 carbon units or less which exhibit carnitine-independent transport into mitochondria were effective substrates for oxidative phosphorylation in both fetal and calf heart mitochondria. Efficient oxidative phosphorylation with these substrates was dependent upon the presence of bovine serum albumin in the assay medium to reverse the uncoupling effects of the fatty acids. In the presence of bovine serum albumin, ADP/0 ratios were in the range of 3 when short-chain fatty acids and carnitine esters of short- and long-chain fatty acids were substrates. Compared with calf heart mitochondria, fetal heart mitochondria showed decreased carnitine-dependent oxidation of palmityl-CoA. However, the oxidation of palmitylcarnitine was identical in both. These data suggest that the formation of palmitylcarnitine is rate limiting for palmityl-CoA oxidation by the fetal heart mitochondria and that long-chain fatty acids are not readily oxidized by the fetal heart.

Adverse effects of outpatient parenteral antibiotic therapy.

PURPOSE: Although home parenteral antimicrobial therapy has become common, few studies have carefully examined its adverse effects. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 269 patients who received 291 courses of home parenteral antimicrobial therapy through a hospital-based home infusion program during a 2-year period. Patients with human immunodeficiency virus (HIV) infection were not included. RESULTS: The majority (59%) of patients were treated for bone and joint infections. Patients had a mean age of 47 years. The mean duration of antibiotic therapy was 40 days. Of monitored courses, leukopenia occurred in 16%, neutropenia in 7%, thrombocytopenia in 4%, and eosinophilia in 12%, usually after a month of therapy; these adverse effects were most frequently associated with the use of beta-lactam antibiotics. Nephrotoxicity occurred in 8% of monitored courses at a mean of 27 days and was most commonly associated with amphotericin B. Diarrhea occurred in 7% and rash in 4% of patients, and both were most commonly seen with beta-lactam antibiotics. Of those patients with permanent indwelling catheters, 11% of those with central catheters and 9% of those with peripherally inserted central catheters (PICCs) developed line complications. Overall, 8% of patients required rehospitalization. CONCLUSION: Home infusion antibiotic therapy exposes patients to the complications associated with inpatient antibiotic therapy and needs to be monitored closely to prevent serious complications and rehospitalizations.

Epinephrine is unessential for stimulation of liver glycogenolysis during exercise.

To determine the role of adrenal medullary hormones in controlling the rate of liver glycogenolysis during exercise, adrenodemedullated (ADM) and sham-operated (SO) rats were run on a rodent treadmill at 21 m/min up a 15% grade for 0, 30, or 60 min. Rats were anesthetized by intravenous injection of pentobarbital sodium, and liver, muscle, and blood were collected and frozen. Liver glycogen decreased at similar rates in ADM and SO rats. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP), plasma glucagon, and plasma free fatty acids increased to the same extent in both ADM and SO rats. The adrenodemedullation caused a reduction in glycogenolysis in the fast-twitch white region of the quadriceps, soleus, and lateral gastrocnemius during exercise. The normal exercise-induced increase in blood glucose and lactate and the decline in plasma insulin were not observed in the demedullated rats. During submaximal exercise the principal targets for epinephrine released from the adrenal medulla appear to be pancreatic beta-cells and skeletal muscle and not the liver.

Tobacco. Its impact on vascular disease.

The role of smoking in vascular disease is multifactorial and complex. Research continues to further elucidate the mechanisms involved and advance treatment options. What remains clear throughout is that smoking cessation has multiple health benefits. In a recent public health projection study of mortality and disability by cause, tobacco use was marked as the potentially largest health problem to be expected in the year 2020. Although smoking cessation is not simple, in the years spanning 1993 to September 1997, 1720 articles were published under the key words "smoking cessation," reflecting the difficulty of this endeavor and lack of a satisfying answer to this health problem. Nonetheless, approaches to patient smoking cessation should be attempted by all physicians. A protocol for physicians to assist patients with smoking cessation from the National Cancer Institute can serve as a general guide (Fig. 3). Some of the programs available to assist patients in smoking cessation are listed in Table 7.

Effectiveness of products in eliminating cat urine odors from carpet.

Eleven products were compared for their ability to eliminate cat urine odor in carpet. Their performance on new urine spots and on old spots was compared as was their ability to prevent the return of urine odors after the carpet was cleaned. Newer products marketed to eliminate urine odor did the best in getting rid of and in preventing the return of urine smells. Other products also scored well. A few products were considered to be of little value for the removal of urine odor in carpet.

Role of plasma epinephrine in fasted exercising rats.

We have investigated the physiological role of the marked increase in plasma epinephrine that occurs in fasted exercising rats. Fasted adrenodemedullated (ADM) rats show a marked reduction in endurance run times compared with sham-operated (SO) controls. After running for 30 min at 21 m/min up a 10% grade, ADM rats' blood glucose was 2.9 +/- 0.1 mM vs. 4.3 +/- 0.2 mM in SO rats. At the same time, blood lactate was 3.0 +/- 0.2 mM in SO rats compared with 1.0 +/- 0.1 mM in ADM rats. Glycogenolysis was impaired in ADM rats in the fast-twitch white region of the quadriceps, lateral gastrocnemius, and soleus muscles but not in the fast-twitch red region of the quadriceps muscle. Hepatic adenosine 3',-5'-cyclic monophosphate was increased to the same extent in ADM and SO rats during exercise. Infusion of epinephrine into ADM rats during exercise corrected the hypoglycemia, restored lactate to normal, and stimulated glycogenolysis in soleus, white quadriceps, and lateral gastrocnemius muscles. Epinephrine-dependent glycogenolysis in contracting type I and noncontracting type II muscle fibers apparently provides essential quantities of lactate for hepatic gluconeogenesis in fasted exercising rats.

Diacylglycerols modulate insulin action in rat adipocytes.

Effect of 1,2-diacylglycerols on the insulin receptor function and insulin action in rat adipocytes was studied. 1,2-dioctanoylglycerol (100 micrograms/ml) did not alter insulin binding but it did stimulate phosphorylation of the beta-subunit of the insulin receptor as well as its tyrosine kinase activity. However, dioctanoylglycerol inhibited insulin-stimulated receptor autophosphorylation. This concentration of dioctanoylglycerol inhibited insulin-stimulated CO2 metabolism, lipogenesis and 3-O-methyl-glucose transport in a dose-dependent manner but did not alter any of these bioeffects in absence of insulin. While there was no direct link between diacylglycerol effect on tyrosine kinase activity of the insulin receptor and insulin action in rat adipocytes, the parallel inhibition of insulin-stimulated receptor autophosphorylation and insulin bioeffects by dioctanoylglycerol suggests its direct or indirect role in insulin signalling in rat fat cells.

Metabolic adaptation in developing lung.

We have carried out studies using rat lung slices showing that the developing lung utilizes both glucose and fatty acids as oxidative substrates. Glucose oxidation to CO2 decreased at birth but showed higher activity after weaning. The activity of the pentose phosphate pathway also decreased postnatally. In contrast to glucose, the oxidation of palmitate and caprate to CO2 showed an increase in the immediate postnatal period. Cytochrome oxidase and carnitine palmitoyltransferase showed a parallel postnatal increase following the increase in fatty acid oxidation. Cytochrome oxidase activity in adult lung was approximately 30% of peak newborn values. Palmitate incorporation into total lipids was greatest at 18 to 19 days of fetal development, at which time the lung content of nonesterified fatty acids was highest.

Fatal Vibrio parahemolyticus septicemia in a patient with cirrhosis. A case report and review of the literature.

Vibrio parahemolyticus has been well documented to cause outbreaks of infectious diarrhea, usually related to poor food handling; only rarely has it been reported to cause fetal septicemia. In contrast, Vibrio vulnificus is a well-known cause of septicemia, especially in patients with cirrhosis. A 31-year-old woman with cirrhosis who developed fatal V. parahemolyticus sepsis after ingesting raw seafood is described. We review the clinical syndromes associated with sepsis caused by these two organisms. Leg pain and bullous skin lesions may be a clue to the diagnosis. Febrile patients with cirrhosis should be questioned regarding recent seafood ingestion, and appropriate antibiotics chosen if this history is obtained. Physicians should inform patients at risk to avoid raw seafood in an attempt to prevent this potentially lethal syndrome.