Metabolic responses to fructose-1,6-diphosphate in healthy subjects.

Fructose-1,6-diphosphate (FDP) is an important naturally occurring intracellular metabolite with a direct regulatory role in many metabolic pathways. The most important and widely studied of the FDP effects has been its regulation of glycolysis, particularly the enzyme that synthesizes FDP--phosphofructokinase (PFK). Since it was observed experimentally that FDP does indeed modulate carbohydrate metabolism, we investigated whether FDP would similarly enhance carbohydrate utilization in man. The study used indirect calorimetry and was open to healthy adults (N = 45) of either sex and above legal age. After a steady metabolic state was obtained, 5 g of FDP (10%) was infused into a brachial vein. In 10 subjects, glucose (5 g) or FDP (5 g) was sequentially infused. The rapid intravenous infusion of FDP produced a slight but significant decrease in heart and respiration rates (P < .05). A significant increase in the serum concentration of inorganic phosphate (P < .0001) and the intraerythrocytic concentration of adenosine triphosphate (ATP) (P < .01) was also observed. The FDP infusion produced a decrease in plasma cholesterol and triglycerides (P < .001 and P < .01, respectively). The indirect calorimetric data indicate that the infusion produced a highly significant increase in the respiratory quotient ([RQ] P < .0001) and the energy derived from carbohydrates (P < .0001) and a significant decrease in the energy derived from lipids (P < .0001). Glucose infusion did not cause changes in any of the parameters. These data indicate that carbohydrate metabolism is stimulated by FDP.

Tick paralysis syndrome in a 5-year-old girl.

Tick paralysis syndrome (TPS) is an uncommon cause of ascending paralysis in children. Familiarity with its clinical features is important, since prompt diagnosis and removal of the tick is curative. We report the case of a 5-year-old girl with TPS manifested as lower extremity ataxia and paralysis and briefly discuss the salient features of TPS.

Predicting discharge in uncomplicated near-drowning.

To determine if routine, noninvasive parameters could be measured which predict early (4-6 hour) discharge from the emergency department (ED) in mildly symptomatic and asymptomatic victims of childhood near-drowning, a retrospective cohort study was undertaken. Patients with fresh water near-drowning were studied over a 3-year period who presented with Glascow Come Scale (GCS) > or =13 and required no advanced life support prior to or < or =4 hours after ED presentation. Three groups of patients were found: 39 patients (81%) had normal pulmonary examination (PEx) and normal room air oxygen saturation (RASaO2) by 4 to 6 hours and did not deteriorate during the hospital admission (<24 hours); 5 patients (10%) had normal PEx by 4 to 6 hours and RASaO2 by 8 to 12 hours and did not deteriorate during hospitalization (<24 hours). Four patients (8%) were hospitalized for more than 24 hours. No patient with normal RASaO2 at 6 hours deteriorated while in the hospital (CI 92.3-100%). Children who present to the ED with GCS > or =13 and have normal PEx/respiratory effort and RA-SaO2 more than 95% at 4 to 6 hours after ED presentation can be safely discharged home.

Effect of nebulized albuterol on circulating leukocyte counts in normal subjects.

Nebulized beta 2-receptor agonists may cause neutrophil demargination and result in misleading total circulating leukocyte counts (WBCs) in patients with acute bronchospasm. Varying underlying adrenergic stimulation in these patients also makes interpretation of these data difficult. This study examined the direct effect of these agents on the measured WBCs of healthy adults without evidence of bronchospasm or illness. A prospective, blinded, randomized study of 30 healthy volunteers (aged 18-50 years) was performed in a controlled environment. Subjects were excluded if they were pregnant, had a known underlying medical disorder or have had a prior reaction to albuterol or similar medications. Participants in the study were given either a nebulized albuterol treatment or nebulized normal saline (control group). Leukocyte counts were then obtained before and after treatments. Paired data were analysed using a one-tailed t-test while considering an increase of 40% in WBCs to be significant, P = 0.05, and beta = 0.10. Mean leukocyte counts were 5.9 (+/- 1.2) before treatment as compared to 6.0 (+/- 1.3) after albuterol nebulization. Using the coefficient of variance of WBCs in normal humans as c. 50% (6000 +/- 3000 cells mm-1) we were unable to demonstrate a significant difference in variation in post-nebulized leukocyte counts between the control group and the nebulized albuterol group. While there is concern that the treatment of patients experiencing acute bronchospasm with beta 2 agonists may result in factitious elevations in peripheral leukocyte counts, were found no direct effect of these agents on measured counts in normal subjects.

Effects of oleic acid on murine CD4+ T cell death and anti-CD3 or superantigen induced proliferation at low temperature.

Studies were conducted to examine the effects of low, yet physiologically relevant, temperatures on murine T lymphocyte responses. Akin to ectothermic vertebrate responses, lectin-induced murine T cell proliferation was previously shown to be ablated at temperatures 10 degrees C below optimal (i.e. 27 degrees C); responsiveness at 27 degrees C was restored by the addition of oleic acid (18:1). The aim of the present study was to address the mechanism involved in such low temperature suppression. Murine splenic CD4+ T lymphocytes stimulated with either alpha CD3 or SEB exhibited cell death, as opposed to anergy, at 27 degrees C. However proliferation was observed in the presence of 18:1. Thus low temperature-suppression of murine CD4+ T cells is also mediated through TCR and/or CD3 pathways. Additional studies examining the temporal effects of adding 18:1, as well as temperature shifts, indicated that the cell death induced by stimulation at low temperature was preventable by 18:1.

Pregnant adolescents in the emergency department: diagnosed and not diagnosed.

A study was conducted to compare the presenting complaints and historical information of adolescents diagnosed as pregnant (DP) in the emergency department (ED) with adolescents seen in the ED who were pregnant and not diagnosed (MP). Medical records for the period 1980-94 were retrospectively analyzed to identify patients 16 years of age or younger who were diagnosed as pregnant in the ED or who had a live birth and had an ED visit during pregnancy. This analysis was done in a university-affiliated tertiary referral hospital with approximately 65,000 ED visits and 3,500 deliveries each year. The DP patients had complaints referable to the abdomen or genitourinary system more commonly than the MP patients (91% v 22%). Less than 10% of the DP patients mentioned the possibility of pregnancy at initial triage, 10.5% denied being sexually active, and 5% had a pelvic examination and sexually transmitted disease screening; 68% of MP patients did not have sexual or menstrual history documented, and 5% had a pelvic examination. The diagnosis of pregnancy can be a challenge in patients who present to a busy ED with complaints that are not necessarily suggestive of pregnancy. Historical information regarding menses and sexual activity is either not obtained or is incomplete or inaccurate. We recommend a low threshold for the consideration of pregnancy in adolescents irrespective of the presenting complaint.

PIP: A retrospective study was performed at a tertiary care hospital in Mississippi to compare the emergency room (ER) presenting complaints during 1980-1994 of the 171 pregnant adolescents 16 years old and younger whose pregnancies were diagnosed with the 100 whose pregnancies were not diagnosed. Data were collected from the medical records of those diagnosed as pregnant and from the 2945 records available of the 4125 patients under 16 who delivered babies at the hospital during the same period. It was found that 100/2945 were seen in the ER while pregnant but the pregnancy was not diagnosed. It was found that 91% of the pregnancy diagnosed patients versus 22% of the missed diagnosis patients had complaints relating to the abdomen or genitourinary system. Less than 10% of the diagnosed patients indicated the possibility of pregnancy at the initial examination, and 10.5% denied being sexually active. No sexual or menstrual history was documented for 68% of the missed diagnosis patients, and 5% of each group had pelvic examinations. No significant differences were found for patient age or demographics, gestation at ER visit, or gestation at delivery. In 30 cases of missed diagnoses (all with gestation at 8 weeks or more), 23 presented with abdominal, genitourinary, or mammary complaints, and 7 presented with drug overdoses. In 22 patients, diagnosis was missed even though the pregnancy was at 22 weeks gestation or more. One extraordinary case involved a 14-year-old who was admitted for treatment of a gunshot to the head. Her pregnancy was not diagnosed until her second follow-up visit after a lengthy hospital stay (gestation was 30 weeks at ER presentation). Because many treatments are modified by pregnancy, it is recommended that pregnancy be assumed in all females of child-bearing age presenting to the ER with consideration given to degree of sexual maturity.

Aspirated safety pin requiring thoracotomy: report of a case and review.

Foreign body aspirations in children are relatively uncommon occurrences, but they can be a serious events, causing respiratory distress, atelectasis, chronic pulmonary infections, or death. Safety pins are not commonly aspirated objects and account for less than 3% of all foreign bodies found in the tracheobronchial tree. Fewer than 2% of patients require thoracotomy, and most aspirated materials can be removed by bronchoscopy, with low morbidity and mortality. A discussion of airway foreign bodies follows the presentation of a case of an older child who aspirated a safety pin, which required open thoracostomy for removal.

Intervertebral disk calcification: an unusual cause of acquired torticollis in childhood.

Intervertebral disk calcification in children can result in a syndrome of neck pain, muscle spasm, and torticollis. Usually the clinical course is benign with spontaneous recovery; however, occasionally nerve root or spinal cord compression can be seen. We report a seven-year-old patient with symptomatic cervical disk calcification and briefly discuss the salient clinical and radiographic features.

Pharmacokinetics and metabolism of zamifenacin in mouse, rat, dog and man.

1. Zamifenacin was rapidly metabolized in vitro by liver microsomes from rat, dog, and man. 2. Zamifenacin exhibited extensive plasma protein binding with human plasma showing 20 and 10-fold higher binding that that in rat and dog respectively. 3. Following oral administration to animals, metabolic clearance resulted in decreased bioavailability due to first-pass metabolism in rat and mouse. Oral clearance in man was low as a result of increased metabolic stability and increased plasma protein binding compared with animals. 4. Metabolism was the major route of clearance of zamifenacin with the primary metabolic step resulting in opening of the methylenedioxy ring to yield the catechol. In man, this metabolite was excreted as the glucuronide conjugate, whereas in the animal species it was further metabolized by mono-methylation of the catechol.

Missed slipped capital femoral epiphysis: illustrative cases and a review.

Slipped capital femoral epiphysis (SCFE) is a fairly common condition affecting older children and adolescents, and has the potential for long-term, crippling sequelae. Early recognition is the single most important controllable factor, but the diagnosis is often missed or delayed, resulting in progression of the slip. A SCFE should be suspected and promptly evaluated in any older child or adolescent presenting with a limp or complaints of hip, groin, thigh, or knee pain, especially if the patient is overweight. The diagnosis is usually made by anteroposterior and frog-leg lateral radiographs of the hips. Common errors at initial presentation include: not obtaining hip radiographs (due to either no hip pain or the lack of an impressive history and physical findings); misreading hip radiographs (the findings can be subtle); and lack of timely referral. Early involvement of and treatment by an orthopedic surgeon can greatly reduce the potential complications. We present three cases of SCFE that highlight common errors made at initial presentation, and a discussion that includes the differential diagnosis of an older child or adolescent with a painful limp.

A serum-free medium for human primary T lymphocyte culture.

This paper describes a defined serum-free medium (SFM), designated A-X, which supports in vitro proliferation of human primary T cells stimulated with mitogens, two-way mixed leukocyte reactions, anti-CD3, and a superantigen. A-X is a 1:1 mixture of two commercially available SFM, AIM V and EX-CELL 300. In each assay tested it supported uptake of [3H]thymidine as well as or better than the standard culture medium, namely RPMI 1640 supplemented with 10% fetal calf serum. A-X also allowed the detection of interleukin-2 by ELISA at levels comparable to those produced in serum-supplemented medium. A-X will likely be useful in further studies as it eliminates many of the problems usually associated with the use of serum-supplemented media.

Henoch-Schönlein purpura: four cases and a review.

Henoch-Schönlein Purpura (HSP) is a common, usually self-limited, vasculitis affecting children and young adults. Manifested by a characteristic rash, the course of HSP is typically a benign one, but may be accompanied by varying degrees of abdominal pain, arthritis or arthralgia, gastrointestinal bleeding, and nephritis. The various manifestations of HSP may present at any stage during the illness and mimic other disease processes, some of which may be life threatening. Thus, the emergency physician must consider the diagnosis of HSP in order to detect complications and avoid needless intervention in what usually is an otherwise benign process. We present four cases and a brief review of the literature to highlight HSP in the differential diagnosis of patients who present with any of the typical clinical signs and symptoms.

Evaluation of criteria for the acceptance of bioanalytical data.

Results from bioanalytical analyses for registration of a new drug entity are used to define its pharmacokinetics and bioavailability/bioequivalence. Whilst analytical data may be derived from the application of a validated method, it is essential to apply mathematical criteria to its acceptance, in order that the analyst can be assured that the assay is performing within defined limits and to its validated specification. Parameters evaluated for acceptability are the batch calibration curve, the minimum quantifiable concentration and the quality control (QC) sample acceptability. Specifically, six QC samples per analytical batch are used, two samples at each of three concentrations. The rationale for the definition of these criteria is evaluated together with a consideration of their applications and limitations. The relevance and use of Shewhart and Cusum plots to monitor assay performance is illustrated.

Altered acyl-CoA metabolism in riboflavin deficiency.

We have recently described the effects of riboflavin deficiency on the metabolism of dicarboxylic acids (Draye et al. (1988) Eur. J. Biochem. 178, 183-189). As both mitochondria and peroxisomes are thought to be involved, we have examined the activities of various enzymes in these organelles in the livers of riboflavin-deficient rats. Mitochondrial beta-oxidation of fatty acids was severely depressed due to loss of activity of the three fatty acyl-CoA dehydrogenases, whereas there was an enhancement of peroxisomal beta-oxidation due to an increased activity of the FAD-dependent fatty acyl-CoA oxidase, although the activities of other peroxisomal flavoproteins, D-amino acid oxidase and glycolate oxidase, were lowered. Hepatocyte morphometry revealed an increase in the numbers of peroxisomes, indicating a proliferation induced by the deficiency. The mitochondrial acyl-CoA dehydrogenases involved in branched-chain amino acid metabolism were also severely decreased leading to characteristic organic acidurias. There was some loss of activity of the flavin-dependent sections of the electron transport chain (complexes I and II), but these were probably not sufficient to affect normal function in vivo. The specificity of these effects allows the use of the riboflavin-deficient rat as a model for the study of dicarboxylate metabolism.

A study of the metabolism of [U-14C]3-methyl-2-oxopentanoate by rat liver mitochondria using h.p.l.c. with continuous on-line monitoring of radioactive intact acyl-coenzyme A intermediates.

A reverse-phase h.p.l.c. system for the resolution of the acyl-CoA intermediates of the degradation of 3-methyl-2-oxopentanoate is described. The validation of a method for the measurement of radioactive intermediates produced by the incubation of [U-14C]3-methyl-2-oxopentanoate with rat liver mitochondrial fractions is described. The absence of bicarbonate caused the accumulation of [14C]propionyl-CoA. The accumulation of [14C]2-methylbutyryl-CoA was observed in incubations with mitochondrial fractions derived from riboflavin-deficient animals. Studies of the accumulation of labelled intermediates with time suggest that there is regulation of the pathway of isoleucine degradation at methylmalonyl-CoA mutase, as suggested for valine [Corkey, Martin-Requero, Walajtys-Rode, Williams & Williamson (1982) J. Biol. Chem. 257, 9668-9676]. These studies demonstrate that h.p.l.c. with on-line continuous radiochemical detection is a powerful method for the investigation of the control of intermediary metabolism.

A comparison of four commercial test kits for detection of cytomegalovirus antibodies in blood donors.

Four commercial test kits for detecting cytomegalovirus (CMV) antibodies (indirect hemagglutination assay, indirect fluorescent antibody technique, enzyme immunoassay, and passive latex agglutination technique) were compared according to their technical demand, hands-on time, turnaround time, concordance with other techniques, reagent cost per test, and objectivity. The indirect hemagglutination assay, the enzyme immunoassay, and the passive latex agglutination technique produced identical results in 85 donors, detecting 63 positive and 22 negative samples. The indirect fluorescent antibody technique showed discrepant results in four samples. The passive latex agglutination technique rated best overall since it was technically the easiest and required the least hands-on and turnaround times; the short turnaround time (10 minutes) rendered the latex technique a more flexible test for blood bank use because both scheduled and emergency CMV screening of donors could be accommodated. The comparatively high reagent cost of the latex test kit could be offset by savings on technologist time.