Serum levels of myoglobin, creatine phosphokinase, and smooth muscle heavy-chain myosin in patients with ectopic pregnancy.

STUDY OBJECTIVE: Serum markers of smooth muscle destruction have been shown to be elevated in ectopic pregnancy, but they remain of questionable clinical utility. Our goal was to determine the clinical utility of 3 markers of smooth muscle destruction: creatine phosphokinase (CPK), smooth muscle heavy-chain myosin (SMHC), and myoglobin. METHODS: This was a prospective cohort study, with consecutive enrollment of all women in the first trimester of pregnancy who presented to our urban emergency department with complaints of lower abdominal pain, vaginal bleeding, or both. Patients were excluded from the study if there was a history of recent surgery or major trauma. Data analysis included receiver operating characteristic (ROC) curve, 95% confidence intervals (CIs), and a regression model. RESULTS: A total of 378 patients were enrolled, with 61 patients diagnosed with an ectopic pregnancy, and 317 patients placed in the non-ectopic pregnancy group with other diagnoses. ROC curve analysis revealed an area under the curve of 0.56 (95% CI 0.51 to 0.61) for CPK, 0.63 (95% CI 0.59 to 0.68) for SMHC, and 0.58 (95% CI 0.53 to 0.63) for myoglobin. A regression model analyzing the effects of race, maternal age, estimated gestational age, and serum levels of human chorionic gonadotropin beta-subunit found no significant confounders. CONCLUSION: Although there is a statistically significant elevation in the serum levels of SMHC, the range of values seen is too large to allow SMHC to be a useful screening tool.

The utility of maternal creatine kinase in the evaluation of ectopic pregnancy.

This investigation was designed to evaluate the utility of maternal creatine phosphokinase (CPK) in predicting the presence of an ectopic pregnancy (EP) in an emergency department (ED) setting. Twenty-one patients with the diagnosis of EP were randomly matched (1:1) with pregnant patients who subsequently ruled-out for EP. Serum CPK values at presentation were compared between the groups using two-tailed ANOVA, odds ratio, and frequency tables were generated using our a priori hypothesis that a serum CPK of >70 mlU/dL may be useful as a predictor of EP. The mean serum CPK was 118mlU/dL in the EP group and 64 mlU/dL in the non-EP group (P < .0031). Controlling for age, race, and gestational age, there was an association between elevated serum CPK and EP in our study population (with an odds ratio of 6.5). The categorical evaluation (with 95% confidence interval [CI]) of CPK (>70 mIU/dL) as a predictor of EP follows: sensitivity - 100% (80.8 to 100); specificity-- 61.9% (38.7 to 81); PV(+) - 72.4% (52.5 to 88.6); PV(-) - 100% (71.7 to 100). We therefore conclude that a CPK level >70 mIU/dL may serve as an important adjuvant diagnostic tool in ruling-out EP.

Thyrotoxic periodic paralysis and intravenous propranolol in the emergency setting.

A 27-year-old male of Malaysian descent presented to the Emergency Department (ED) with rapidly progressive flaccid paralysis that quickly compromised his respiratory effort. The patient was found to have a serum potassium of 1.9 meq/L, and was diagnosed as having an acute paralytic episode secondary to thyrotoxic periodic paralysis. The paralytic attack was aborted with a combination of potassium replacement and parenteral propranolol in large doses. We report the use of a rarely described, yet possibly more effective, therapy for an acute attack of thyrotoxic periodic paralysis.

Synthesis and intravenous infusion into the rat of glyceryl bisacetoacetate, 1-acetoacetamido-2, 3-propane diol, and partially reduced glucosyl pentaacetoacetate.

The efficacy of parenteral nutrition could be improved by finding a more effective energy source. Esters of short-chain fatty acids have exhibited some promise as alternatives to glucose. The present study reports on two new esters and one amide, each containing acetoacetate as the organic acid. The three compounds: glyceryl bisacetoacetate, N-2',3'-dihydroxypropyl-3-oxo-butanamide (1-acetoacetamido-2,3-propane diol), and partially reduced glucosyl pentaacetoacetate, were synthesized and then continuously infused into rats for 7 d. The infusion rate provided 50% of the rats' estimated metabolic energy requirements, and rats were fed with a reduced-energy oral diet that provided the remaining 50% of energy plus adequate protein. Rat groups for each compound were: (1) experimental-compound-infused and ad libitum-fed, (2) isoenergetic glucose-infused and pairfed, and (3) saline infused and pair-fed. Body-weight changes, N losses and N retention were measured daily. All rats died from partially reduced glucosyl pentaacetoacetate infusion at 100% and 50% of the intended rate. Rats infused with 1-acetoacetamido-2,3-propane diol failed to gain weight and to increase the plasma ketone-body concentration. Glyceryl bisacetoacetate produced hyperketonaemia, and weight gain and N variables that were similar to those for glucose-infused rats. It was concluded that only glyceryl bisacetoacetate would make a satisfactory parenteral nutrient.

Branched-chain transaminase and keto acid dehydrogenase activities in burned rats: evidence for a differential adaptation according to sex.

Female and male rats show differences in nitrogen metabolism after trauma, and the contribution of the branched-chain amino acid oxidizing pathway following thermal injury was evaluated. Female and male rats were subdivided into baseline, burned and unburned, pair-fed groups. Burned and pair-fed rats were sacrificed on days 1, 2, and 3 postburn, and branched-chain amino acid transaminase (BCTA), branched-chain alpha-keto acid dehydrogenase (BCKDH) activated and total, and succinate dehydrogenase (SDH) activities were measured in red and white muscle and in liver, BCTA was not measured in liver. Baseline and pair-fed groups had similar enzyme activities. Changes following thermal injury were: (1) elevated SDH in all tissues for both sexes; (2) increased BCTA activity in red and white muscles from male rats; and (3) increased percentage of activated BCKDH in red and white muscles on days 2 and 3 for male rats. All other activities were unchanged. These findings agree with previous post trauma differences in urinary nitrogen losses in female and male rats. The results show that the enzymes for oxidation of the branched-chain amino acids in males respond to injury while those do not in females.

Potential of the monoglyceride and triglyceride of DL-3-hydroxybutyrate for parenteral nutrition: synthesis and preliminary biological testing in the rat.

Esters of short-chain organic acids have shown some promise as potential nutrients for parenteral feeding. Most glycerols are water insoluble but those of the ketone bodies have some water solubility. Of interest is that the triacylglycerol of 3-hydroxybutyrate has water solubility while the triacylglycerol of acetoacetate does not. The mono- and triacylglycerol of DL-3-hydroxybutrate were synthesized and tested for toxicity and nutritional value as parenteral nutrients. Both compounds have an estimated energy density of 19.7 kJ/g (4.7 kcal/g) and are water soluble. The compounds were infused into rats for 7 d at a rate to provide 113 kJ/d and were accompanied by a low-energy oral diet. Control, pair-fed rats were infused with isocaloric glucose or 0.9% saline. Nitrogen intake, output, and balance, body weight changes, and liver size were compared. The two glycerols of 3-hydroxybutyrate supported similar nitrogen retention, body weight changes, and liver size as found in the pair-fed control animals infused with glucose. Rats infused with saline retained less nitrogen, had decreased body weight, and had smaller livers. The data demonstrated that the glycerols of DL-3-hydroxybutyrate are not toxic, provide metabolic energy when infused intravenously, and could be used as nutrients for parenteral feeding.

Energy charge and mitotic activity in regenerating rat liver during parenteral nutrition.

The relationship among parenteral nutrition, hepatic energy charge, and mitotic activity was investigated in partially hepatectomized rats fed diets based on glucose, ketone bodies, and saline (starvation). Male Sprague-Dawley rats underwent 70% hepatectomy and jugular vein catheterization for parenteral feeding. All rats were infused with saline for 6 hours, then randomly assigned to one of three parenteral infusions. Rats received either 0.9% saline only (group A rats), 25% glucose + 4% amino acid (group B rats), or 18% monoacetoacetin + 7% glucose + 4% amino acid (group C rats). Three rats receiving saline infusion were killed at 2, 4, and 6 hours after surgery, and three rats from each diet group were killed at 2- to 4-hour intervals from 10 through 32 hours. Hepatic energy charge and mitotic index were measured at each time point. Energy charge was similar for each treatment until 18 hours but was depressed from 6 through 16 hours and began to increase between 16 and 18 hours. Energy charge at 22 hours for group B rats was significantly higher than energy charge for group A and C rats. This difference was maintained through 32 hours. Mitosis started between 24 and 26 hours for all treatments, and group A and C rats exhibited a much higher mitotic index than did group B rats. Adenosine triphosphate was the main driving force for changes in energy charge. The data showed that energy charge and mitotic index were inversely related. It is speculated that high energy charge may negatively influence activity of enzymes inasmuch as activity of these enzymes is altered by phosphorylation-dephosphorylation.

Parenteral monoacetoacetin and liver regeneration interaction after partial hepatectomy in the rat.

Parenteral nutrients can be used to manipulate cell proliferation after partial hepatectomy. The relationship among macronutrients--glucose, monoacetoacetin, amino acids--and liver regeneration after partial hepatectomy was investigated. Male rats were anesthetized, received a 70% hepatectomy, and received a low-dose infusion of (1) glucose or (2) monoacetoacetin and a high-dose infusion of (3) glucose, (4) glycerol-glucose, or (5) monoacetoacetin-glucose beginning 6 hours after surgery. The five nonprotein nutrient combinations were infused with and without amino acids. Rats were killed 48 hours after partial hepatectomy, and the label and mitotic indices were determined. Each of the five treatments had a higher label index with amino acids present than with amino acids absent. Low-dose glucose and monoacetoacetin as well as high-dose glucose and glucose-glycerol had higher mitotic indices with amino acids than without amino acids. High-dose monoacetoacetin-glucose was associated with a greater mitotic index than was any other nonprotein substrate treatment, and this response was independent of amino acids being present or absent. In summary, (1) amino acids were needed for maximal cell proliferation rate; (2) the absence of amino acids and not the presence of glucose resulted in reduction of the label and mitotic indices for regenerating liver; (3) high-dose monoacetoacetin increased mitosis with or without amino acids; and (4) monoacetoacetin activity was dose dependent. The results indicate that the best nutrient for treatment of patients with liver injury is acetoacetate. The second best nutrient would be the combination of high-dose glucose and amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic rate and nitrogen balance after skeletal trauma in female and male rats.

Unequal metabolic responses to trauma by women and men have been suggested, but an explicit investigation demonstrating this conjecture has not been made. The responses of resting energy expenditure (REE) and nitrogen balance for 3 days before and 7 days after skeletal trauma were determined for female and male rats. Food intake and body weight were recorded daily, and 24-h urine samples were collected. Baseline REE and nitrogen balance were obtained for 3 consecutive days before induction of trauma. Then rats were divided into female trauma (n = 8), male trauma (n = 7), female control (n = 8), and male control (n = 7) groups. Trauma was produced by bilateral femoral fracture to anesthetized rats. Control rats were anesthetized without skeletal trauma. Traumatized rats were fed ad libitum for 7 days, and control rats were pair fed with the traumatized rats. The results showed that REE increased and nitrogen balance decreased in traumatized male rats relative to their controls. Traumatized female rats had increased REE and unchanged nitrogen balance compared with their controls. Traumatized female rats had a larger percentage increase in REE on days 5 through 7 than did traumatized male rats. These findings demonstrate a difference between female and male rats in response to trauma. Female rats use more energy and lose less nitrogen after trauma than do male rats. The results suggest that recommendations for increased energy and protein needs after trauma should consider the sex of the subject intended to be fed.

Palmitic acid kinetics in fasting, traumatized patients.

The contribution of free fatty acid oxidation to the elevation in energy expenditure after trauma has not been well characterized. Six control subjects and six traumatized patients were fasted for 48 hours and given a primed continuous infusion of (1-14C)palmitate to measure plasma palmitate and total free fatty acid kinetics. Traumatized patients had greater urinary nitrogen losses (20.8 vs. 9.3 g N per day) and a significantly greater ratio of measured to predicted resting energy expenditure (+36% vs. -6%) compared with controls. Individual and total plasma free fatty acid concentrations were similar for the two groups. The turnover and oxidation of plasma palmitate and total free fatty acids were not changed by multiple trauma. These results demonstrated that plasma free fatty acids and palmitate do not contribute to increased energy expenditure following trauma.

Palmitate and stearate kinetics in the rat during sepsis and trauma.

Kinetics of plasma free palmitate and stearate were measured in control and septic-traumatized rats to determine the contribution plasma free fatty acids make to increased resting energy expenditure. Measurements were made at 24 hr after insult using a primed, 4-hr continuous infusion of selected (1-14C) fatty acid. The plasma concentration of palmitate was increased and stearate was decreased in sepsis-trauma rats compared to plasma concentrations in healthy control rats. Fatty acid turnover rates during sepsis-trauma were changed from control turnover rates in the same direction as plasma concentrations. Oxidation rates for palmitate and stearate at 24 hr after induction of sepsis-trauma were not different from oxidation rates in control rats. Plasma free fatty acids were concluded not to exhibit increased oxidation after sepsis-trauma and not to contribute extra energy during hypercatabolism. This finding contrasts with glucose and amino acids which have an increased oxidation rate during hypercatabolism.

Feeding the rat intravenously with ketone bodies following colon anastomosis.

Ketone bodies are an important metabolic fuel for the gastrointestinal system and as a consequence may promote colonic healing. Ketone bodies and glucose were compared in a dose dependent manner as nonprotein fuels for support of resected colon. Rats had their descending colons resected and received all nutrients by vein for 5 days postoperation. Colonic healing was evaluated from the air pressure required to break the wound. All rats received constant nutrients except for non-protein energy which was fed at 10.5, 21, 31.5, and 42 kcal/day using either glucose or monoacetoacetin as substrate. Colonic bursting pressure was measured on day 5 after surgery. When energy intake was 21 kcal/day or greater, the bursting pressure was two-thirds of nonwounded tissue and was independent of energy quantity and source. At 10.5 kcal/day, bursting pressure for glucose-fed animals was similar to that for animals with no added nonprotein energy while, in contrast, bursting pressure for animals fed monoacetoacetin was similar to that for animals fed 42 kcal/day. It was concluded that bursting pressure was influenced by dietary intake only if the energy intake was sufficiently low, and then ketone bodies were better than glucose for support of colonic healing.

Interaction of ketosis and liver regeneration in the rat.

Monoacetoacetin, the monoglyceride of acetoacetate, was investigated as a nutritional support for the regenerating liver. Following partial hepatectomy, rats were either fed an oral diet ad libitum or administered by total parenteral feeding glucose alone, monoacetoacetin-glucose mixture, or lipid emulsion-glucose for the nonprotein calories. Five rats from each treatment were killed at 6-hr intervals beginning 12 hr after partial hepatectomy and ending at 72 hr. The number of cells synthesizing DNA and the number of cells in mitosis were compared. Rats fed orally or infused with glucose alone or with lipid emulsion had similar parameters throughout. Rats infused with monoacetoacetin had approximately double the number of cells in mitosis and DNA synthesis compared to the other treatments. This stimulation by monoacetoacetin persisted 72 hr. It was concluded from the data that acetoacetate was the agent responsible for increased DNA synthesis and mitosis, but the mechanism for the stimulation was not identified.

Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin.

Total parenteral nutrition (TPN) is associated with intestinal mucosal atrophy. Acetoacetate is oxidized in preference to glucose by both enterocytes and colonocytes and is not present in TPN. The purpose of this study was to determine whether replacement of a portion of glucose calories with monoacetoacetin, the glycerol ester of acetoacetate, could inhibit TPN-associated intestinal atrophy. Male Sprague-Dawley rats (200-250 g) underwent superior vena caval cannulation and were assigned to receive chow ad libitium (CHOW), TPN with 0.86 M monoacetoacetin (ACAC), or TPN with 0.86 M glycerol to control for the glycerol component of monoacetoacetin (GLYC). Nitrogen balance was measured over 7 days after which time the animals were weighed and sacrificed. Jejunal and colonic segments were harvested and the mucosal weight, protein, RNA, and DNA contents measured. All groups showed comparable weight gain. Cumulative nitrogen balance was positive for both TPN groups. Significant decreases in mucosal parameters occurred in both TPN groups compared to the CHOW group, but atrophy was significantly inhibited in both jejunum and colon of the ACAC group compared to the GLYC group. Thus, the substitution of monoacetoacetin for glucose calories in parenteral nutrition solutions inhibited TPN-related atrophy of intestinal mucosa while maintaining normal growth.

Evaluation of free fatty acid kinetics during TPN feeding of healthy rats.

Free fatty acid (FFA) kinetics were evaluated in TPN-fed healthy rats using a single fatty acid tracer. Rats were divided into three groups according to the nonprotein energetic substrate infused: glucose (A), monoacetoacetin-glucose (B), and lipid emulsion-glucose (C). Fat kinetics were measured by continuous infusion of [1-14C]palmitate. Total FFA and individual FFA concentrations were measured and turnover and oxidation were determined for the total pool of FFA and for palmitate. Groups A and B were similar in all parameters. Group C had increased total and individual FFA concentrations. Group C appeared to have decreased total plasma FFA turnover and unchanged oxidation compared to groups A and B. Palmitate appeared to have a 400% increase in oxidation and a 50% increase in turnover for rats in Group C when compared to Groups A and B. It is concluded that a single tracer does not accurately reflect plasma FFA during TPN using lipid emulsion.

The influence of ketosis on the metabolic response to skeletal trauma.

Intravenous glucose and ketone body feeding were compared for their potential in altering urinary nitrogen losses by the traumatized rat. Eighteen male rats were traumatized by bilateral femoral fracture. The rats were fed totally by vein for 3 days prior and 3 days after injury and the infusion rate was held constant over the 6 days of infusion. Group GT rats were fed glucose as the source of nonprotein energy while group MT rats were fed a mixture of 72% monoacetoacetin (the monoglyceride of acetoacetate)-28% glucose for the nonprotein energy. Total urinary nitrogen excretion on a 24-hr basis was measured for each of the 6 days of intravenous feeding. On the third day post-trauma, each rat was evaluated for leucine kinetics using a continuous infusion of L-[1-14C]leucine and measurement of breath and plasma specific activities. Rats from group MT were hyperketonemic and normoglycemic and rats from group GT were normoketonemic and hyperglycemic. Urinary nitrogen losses, leucine oxidation, and leucine turnover were similar for the two groups. We conclude that ketone bodies are as good an intravenous source of energy as is glucose, and the ketone bodies do not cause hyperglycemia.

Total parenteral feeding of rats with an acetoacetate monoglyceride and glucose mixture.

Total parenteral nutrition (TPN) by means of monoacetoacetin (glycerol monoacetoacetate) was compared with TPN by using glucose-glycerol. Growth and urinary nitrogen, copper and zinc over 7 d and leucine dynamics on the last day were studied. Complete intravenous diets were administered to five groups of rats which were differentiated by receiving 45 kcal/d (group A) or 65 kcal/d (group C) from a 50% glucose-50% glycerol mixture, 45 kcal/d (group B) or 65 kcal/d (group D) from a 67% monoacetoacetin-33% glucose mixture, or 45 kcal/d (group E) from 100% monoacetoacetin. Leucine kinetics were determined by continuous infusion. Animals from groups A and C were hyperglycemic and normoketonemic, groups B and D were normoglycemic and hyperketonemic, and group E tended to be normoglycemic and hyperketonemic. Group B rats gained weight and retained the most nitrogen while groups A and E lost weight and groups C and D maintained their weight. Nitrogen losses correlated with weight changes. Urinary copper and zinc were not increased by giving ketone bodies. Leucine kinetics were found to be low for group C compared to its energy-matched group, and leucine metabolism was not correlated with nitrogen output and growth. The data suggest that a monoacetoacetin-glucose mixture is preferable as a nonprotein energy source for TPN when compared to either substance alone.

Isoleucine and valine oxidation following skeletal trauma in rats.

Nitrogen losses in the urine are derived from amino acid oxidation, and the increased loss of urinary nitrogen during stress indicates accelerated amino acid oxidation. This study compared isoleucine and valine oxidation by traumatized rats with that by pair-fed control rats. Seventy rats received bilateral hind limb fractures and were fed an oral liquid diet ad libitum, and 70 healthy rats were pair-fed with the trauma group. Daily food intake, body weight, and 24-hr urinary nitrogen were monitored for each animal, and isoleucine and valine oxidation were measured on days 1 through 7 postinjury using five rats from each group for each amino acid. Amino acid oxidation was determined from the percentage of dose appearing in the breath during 4 hours following a single injection of C-14 labeled amino acid. Anesthesia had a pronounced effect on all parameters on day 1, and its effects were dissipated by day 2. Skeletal trauma produced elevated urinary nitrogen losses that lasted for 5 days and peaked on day 3. Valine and isoleucine oxidation were increased for 5 days, and the peak increase occurred on day 3 post-trauma. These data show that isoleucine and valine oxidation parallel excessive urinary nitrogen excretion after skeletal trauma and that isoleucine and valine, like leucine, contribute to the increased urinary losses after trauma.